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Clinical Trials: All
IRB No. 01-262-1 (Dr. Marion Frank, PI): Human Salty and Bitter Taste Mechanisms
Study description not available
IRB No. 02-200-1 (Dr. Bruce Liang, PI): Molecular Correlates of Atrial Fibrillation
Study description not available
IRB No. 02-288-2 (Dr. Jayesh Kamath, PI): Oral Epithelial Cell Cytokines Candida and PMN Activation
This is a research study that examines the ways by which human blood cells fight yeast infections of the mouth. More specifically, we are interested in the activation of human cells in response to mucosal cell products called cytokines.
IRB No. 03-007-1 (Dr. Ernst Reichenberger, PI): Genetic Analysis of Human Disorders: Keloid Formation
The purpose of this study is to identify genes which cause or contribute to keloid formation. Keloids are wounds which grow beyond the margin of the original skin wound.
IRB No. 03-008-1 (Dr. Ernst Reichenberger, PI): Genetic Analysis of Human Disorders: Skeletal Disorders
The purpose of this study is the investigation of rare bone disorders such as craniometaphyseal dysplasia, cherubism, aplasia cutis congenita, gnathodiaphyseal dysplasia.
IRB No. 03-203-2 (Dr. Daniel Rosenberg, PI): Identification and Analysis of Aberrant Crypt Foci in Colonoscopy Patients
Study description not available
IRB No. 07-016-1 (Dr. Martin Freilich, PI): Osteoporosis and bone augmentation/implant outcomes: An observational study
The objective of this study is to utilize a clinical study model to collect descriptive data needed to support the development of future studies that will test the association between specific measures of bone health and the successful integration of new bone from bone augmentation procedures. Postmenopausal women with a wide range of bone health and reduced jaw bone thickness will receive bone augmentation therapy followed by implant and restoration placement, with the specific treatment based upon best clinical judgment. Throughout initial diagnosis, treatment and follow-up, blood makrers will be drawn to assess bone health and its possible association with treatment outcomes. Outcomes will be based upon clinical and radiographic examination, bone health markers and patient interviews.
IRB No. 08-207-2 (Dr. Robert Arciero, PI): Multi-Center ACL Revision Study (MARS)
This is a multi-center, prospective, longitudinal, outcomes study with an invisted cohort group of participants undergoing ACL revisions, elective, standard of care (SOC) orthopedic knee surgery. Predictors of outcomes (QOL and premature osteoarthritis) have yet to be determined. The American Orthopaedic Society for Sports Medicine have set up, this multi-center evidenced based registry to recruit approximately 1,200 participants who will be followed out for 2-3 years.
IRB No. 07-252-2 (Dr. Bruce Liang, PI): Circulating Markers for Ischemic Heart Failure
The purpose of this research is to determine if two proteins in the blood are increased during acute myocardial infarction and whether their levels are higher in those who develop heart failure than those who do not. These two proteins are produced and potentially released when the heart muscle is damaged. They may then be released into the blood and be detected by standard method in the research laboratory. At this time, detection of an increase in these proteins in the blood is not know to be associated with any disease or myocardial infarction.
IRB No. 08-280-2 (Dr. Daniel Connor, PI): Assessment of Children in Outpatient Psychiatric Treatment
The study aims to analyze medical chart data from two child psychiatry outpatient clinics. The goal of the study is to learn about the characteristics and needs of children in outpatient psychiatric treatment and their families and who they respond to different forms of psychiatric and psychological treatment, in order to improve treatment services.
IRB No. 08-310-1 (Dr. Marilyn Sanders, PI): UCONN Health Center Research Tissue Registry/Repository
The objective of this project is to develop a research repository for the purpose of performing cancer studies. Information will be gathered form UCHC medical records, molecular and pathological analysis of blood collected and tissue gathered during surgical procedures. The tissue will be obtained during surgical procedures the patient may have elected to have performed at the Health Center in the future. The collection of data will also permit review of relevant information to identify patients who may be eligible for future studies, and to seek permission of patients to be contacted to determine their interest in taking part in future studies. De-identified information will be used for approved research studies and to gather pilot data for extra-mural grant applications.
IRB No. 1337-85-1 (Dr. Victor Hesselbrock, PI): (1) Neuroelectric Correlates of Risk for Alcohol Dependence (2) Deviance Proneness and the Risk for Alcohol Dependence
Study description not available
IRB No. 07-224-2 (Dr. Augustus Mazzocca, PI): The in vitro effect of biomaterials on human osteoblast, tenocytes and chondrocyte cultures
In this study the goal is to evaluate in vitro, biomaterials, using primary osteoblasts, tenocytes and chondrocytes abtained from discarded tissue samples during orthopaedic procedures.
IRB No. 11-027-2 (Dr. Susan Tannenbaum, PI): UCHC Cancer Center Research Screening
Study description not available
IRB No. 11-151-2 (Dr. Vincent Williams, PI): Hip and Knee Outcome Registry
Patients that have their hip or knees replaced by Dr. Williams or Dr. Lindsay have the option to enroll in the registry.
IRB No. 12-009-2 (Dr. Mark Metersky, PI): Bronchiectasis Research Registry: A Consolidated Database of Non-Cystic Fibrosis Bronchiectasis Patients from Major Clinical and Research Institutions
Study description not available
IRB No. 13-061-6 (Dr. Biree Andemariam, PI): CASIRE Sickle Cell Renal Disease Cohort International Study Protocol
Study description not available
IRB No. 13-119-2 (Dr. Bruce Liang, PI): Study of Circulating Monocytes in Patients with Coronary Artery Disease
Study description not available
IRB No. 14-024-2 (Dr. Adam Adler, PI): In vitro characterization of cancer related immune impairment and its reversal by the use of cytokines, costimulatory molecules and a blocker of immune suppression used singly or in combination
The trial will include patients with advanced malignancy and an estimated survival of 6 months or less, based on the judgment of their oncologist, the type of malignancy, ECOG performance status, stage of disease and pre-existing co-morbidities. This is an exploratory in-vitro study which is being performed to determine optimal combinations of cytokines, costimulatory agonists and inhibitors of immune-suppressive factors to restore immune responsiveness in patients with advanced malignancy. Patients meeting the “inclusion and exclusion criteria” will be solicited by their physician or designee to allow a venipuncture and withdrawal of 20cc of blood. The samples will be obtained, as much as feasible, along with routine blood work, so as to minimize the need for additional venipuncture. The lymphocytes will be isolated and exposed to cytokines, including, but not limited to, members of the IL1 family of cytokines [IL 1, IL 18, and IL 33. IL 36]. The cells will also be exposed to agonists for costimulatory molecules of the TNF family, including but not limited to, OX-40 and 4-1-BB. Costimulatory agonists and antagonists to B7 family will also be used, including but not limited to PD1, PD2, PD1L and CD28. An inhibitor of IDO will also be used to reduce the suppressive effects of Tregs and MDSC. The T-cells will be stimulated by vaccine recall antigens, such as tetanus toxoid and influenza antigen. Mitogens such as PMA plus Ionomycin and/or anti-CD3 monoclonal antibody will also be employed. Ki-67 staining, a marker of cell proliferation will be done to determine a Ki-67 labeling index on the study and control specimens before and after experimental manipulations. Measurements of T cell cytotoxicity and quantification of expression levels of cytotoxic effector molecules will be performed before and after experimental manipulations. RNA-Seq will be done before and after experimental manipulations of the study and control specimens to determine which genes are being transcribed in response to experimental measures. Control samples will be obtained from de-identified blood purchased from the GRC. These control specimens will be stimulated and activated in a similar fashion to the specimens obtained from the experimental subjects. If possible, the same study patients will be requested to allow a second venipuncture no sooner than 6 weeks after the first venipuncture, and in no case, no sooner than six weeks after the last antineoplastic therapy.
IRB No. 14-056-6 (Dr. Pamela Taxel, PI): Investigation of the Ability of the UCONNS (University of Connecticut OsteoNecrosis Numerical Scale) to Predict the Risk for the Developing Osteonecrosis of the Jaw in Women Receiving Bone-Modifying Therapies for Cancer
The purpose of this proposal is to investigate the risk factors for osteonecrosis of the jaw (ONJ), a known complication of several bone-modifying therapies used in the treatment of advanced cancers. When this complication occurs, it can lead to the discontinuation of important therapy that often impacts the quality of life in skeletal-related events in this population. With the use of a weighted scale that we have devised, the University of Connecticut OsteoNecrosis Numerical Scale (UCONNS), based on known risk factors for ONJ, we aim to validate this scale as a potential predictor of patients at risk, so they may be appropriately monitored and preventative treatment can be initiated. As the medical community has limited guidelines regarding ONJ, we anticipate that this scale, if validated, will foster better communication among providers, as well as improve patient outcomes. This proposal represents a unique collaboration between two investigators in the dental and medical schools at the University of Connecticut Health Center. We hypothesize that the UCONNS can aid in the identification of cancer patients who may be at increased risk for the development of ONJ associated with the use of bisphosphonates and the newer bone modifying therapy, denosumab.
IRB No. 14-057-6 (Dr. Pamela Taxel, PI): Investigation of the Ability of the UCONNS (University of Connecticut OsteoNecrosis Numerical Scale) to Predict the Risk for the Developing Osteonecrosis of the Jaw in Women Receiving Bone-Modifying Therapies for Breast Cancer
The aim of this proprosal is to investigate the risk factors for Osteonecrosis of the Jaws (ONJ), a known complication of several bone-modifying therapies including bisphosphonates and denosumab, a human monoclonal antibody. ONJ is most commonly seen with the use of these medications in the treatment of skeletal related events in cancer patients with metastatic bone disease, and less frequently seen in the treatment of osteoporosis. This complication often causes significant effects on quality of life that may lead to the discontinuation of important disease-modifying therapy. We have recently developed the UCONNS (University of Connecticut OsteoNecrosis Scale) a weighted scale based on known medical and dental risk factors for ONJ that we are currently validating both retrospectively and prospectively for use as a potential predictor of patients at risk, so they may be appropriately monitored and preventative treatment can be initiated. The current proposal aims to add to the UCONNS by prospectively measuring serum bone markers that may prove valuable in predicting patients that are at increased risk for developing ONJ. We will follow patients who are being treated with bone modifying agents in order to prospectively measure and evaluate a panel of unique parameters of bone metabolism to identify potentially predictive serum biomarkers for the development of ONJ. We hypothesize that the UCONNS can aid in the identification of breast cancer patients who may be at increased risk for the development of ONJ associated with the use of bisphosphonates and the newer bone modifying therapy, denosumab.
IRB No. 14-107-6 (Dr. Biree Andemariam, PI): Identification of Patient-specific RBC-endothelial Cell Adhesion Profiles as Markers of Sickle Cell Disease Severity.
The research objective of this proposal is to determine in 25 adult/pediatric SCD patients (1) the relationship between pain severity phenotype and the strength of adhesion between single red blood cells (RBCs) and single endothelial cells (ECs) isolated from peripheral blood and (2) the ex vivo effect of pharmacologic inhibitors on RBC-EC adhesion, creating both a patient-specific adhesion profile and therapeutic signature. The results are expected to lead to novel individually-targeted approaches to inhibit the onset and limit the duration of painful vaso-occlusive episodes (VOEs). Our central hypothesis is that the strength of adhesion between RBCs and ECs at baseline is related to patient-specific pain severity phenotype, resulting in the need for patient-specific drug therapy. To test the hypothesis, we will pursue the following three specific aims: Investigate the relationship between pain severity phenotype and baseline RBC-EC adhesion profile in SCD subjects – We will measure the strength of adhesion between single RBCs-ECs from SCD subjects at baseline. Baseline/steady-state adhesion profiles will be compared on an inter-patient level to determine which adhesion profiles correlate most highly with pain severity phenotype. Assess the association of VOE severity with changes in RBC-EC adhesion from baseline to VOE onset. We will measure the change in strength of adhesion between single RBCs-ECs from baseline to VOE onset. Changes in adhesion will be compared on an inter-patient level to determine whether relative changes in adhesion profile at VOE onset correlate with VOE severity. Test the ex vivo effect of targeted pharmacotherapy on the RBC-EC adhesion profile of SCD subjects – We will measure (at baseline and at VOE onset) the ex vivo inhibitory effect of two known RBC-EC adhesion blockers (propranolol and abciximab) to identify patient-specific anti-adhesive therapeutic signatures.
IRB No. 14-136-6 (Dr. Biree Andemariam, PI): Hemoglobinopathies and Bone Health
This research study has two purposes. The first purpose is to determine whether having sickle cell trait is a risk factor for the development of bone thinning at an earlier age than expected. Nearly 10% of African Americans carry sickle cell trait and most of them are unaware of it. African Americans are less likely to develop thin bones than whites, but if they sustain a bone fracture, they are more likely to die from it. We believe having sickle cell trait may lead to bone thinning and predispose a subset of African Americans to dangerously thin bones. The second purpose is to try to understand why individuals with sickle cell disease have thinner bones than healthy individuals do. Doctors have already discovered that people with sickle cell disease have very thin bones, but they have not determined why. Our study will try to identify whether the bone thinning is from the body not making enough bone or from the body losing bone once it is made.
IRB No. 14-179-1 (Dr. Rajesh Lalla, PI): Oral Microbiome in Head and Neck Cancer Patients
This research study is about the community of germs that live in the mouth (the oral microbiome) and its relationship to oral complications of radiation therapy such as dryness, mouth sores, tooth loss, cavities, gum disease or poor healing of bone. The purpose of this study is to look at changes in the oral microbiome from before radiation therapy until 18 months after radiation therapy to see if certain characteristics of the oral microbiome relate to mouth problems that may occur after radiation therapy. An optional sub-study is about future genetic testing of saliva samples to look for genes that may affect the risk of oral complications of radiation therapy..
IRB No. 15-027-2 (Dr. Susan Tannenbaum, PI): S1207, "Phase III Randomized, Placebo-Controlled Clinical Trial Evaluating the Use of Adjuvant Endocrine Therapy +/- One Year of Everolimus in Patients with High-Risk, Hormone Receptor-Positive and HER2/neuNegative Breast Cancer."
Primary Objective: The primary objective of this study is to compare whether the addition of one year of everolimus (10 mg daily) to standard adjuvant endocrine therapy improves invasive disease-free survival (IDFS) in patients with high-risk, hormone-receptor (HR) positive and HER2-negative breast cancer. Secondary Objectives: a. To compare whether the addition of one year of everolimus to standard adjuvant endocrine therapy improves overall survival (OS) and distant recurrence-free survival (DRFS) in this patient population. b. To evaluate the safety, toxicities and tolerability of one year of everolimus in combination with standard adjuvant endocrine therapy and compare it with standard adjuvant endocrine therapy plus placebo in this patient population. c. To determine whether the benefit of one year of everolimus use in addition to standard adjuvant endocrine therapy varies by recurrence score (RS), nodal status, or other commonly used prognostic factors. d. To evaluate adherence to 1-year treatment of everolimus in comparison to placebo in addition to standard adjuvant endocrine therapy in this patient population. e. To collect specimens in order to evaluate biomarkers of therapeutic efficacy.
IRB No. 09-156H-1 (Dr. Carla Rash, PI): Reward Center
Study description not available
IRB No. 13-132S-2 (Dr. Glenn Konopaske, PI): Enroll-HD: A Prospective Registry Study in a Global Huntington's Disease Cohort
Enroll HD is a worldwide observational study for people with HD and their family members. We are collecting data in an effort to improve our understanding and treatment of HD.
IRB No. 16-055-2 (Dr. David Steffens, PI): Department of Psychiatry: Adult Repository
The purpose of the repository is to prospectively collect biological samples along with clinical data to facilitate future research studies and pilot analysis related to medical and behavioral health research.
IRB No. 16-086-1 (Dr. Kai Chen, PI): Endothelial Dysfunction in Coronary Artery Disease and Diastolic Heart Failure
Congestive Heart failure, including systolic and diastolic heart failure, is a major public health hazard and its prevalence continues to rise. While the mortality of systolic heart failure has significantly reduced over the past decade thanks to the advances in pharmacological therapy, there has not been a single therapy that has shown to be survival benefit on diastolic heart failure. A significant gap in knowledge on diastolic heart failure has to be bridged before we may design a therapeutic strategy to target this disease. Recent elegant studies have revealed evidence of systemic and myocardial inflammation in endomyocardial tissues. A new paradigm of the pathophysiology of diastolic heart failure has been proposed - systemic proinflammatory state, coronary endothelial inflammation, impairment in endothelial-cardiomyocyte nitric oxide signaling, inflammatory cell infiltration and proinflammatory cytokines, collectively lead to diastolic dysfunction. Therefore, our central hypothesis is endothelial dysfunction contributes to diastolic function and clinical exacerbation of heart failure.
IRB No. 16-111-1 (Dr. Efthimia Ioannidou, PI): Novel Paradigm to Improve Inflammatory Burden in ERSD
The study proposes to examine, for the first time in dialysis patients, the short and long-term effect of systemic and repeated oral health interventions on inflammation and clinical oral parameters. The ultimate goal of this proposal is to improve access to oral care and quality of life by implementing continuous and repeated in-center oral health programs in dialysis populations.
IRB No. 16-124-1 (Dr. Upendra Hegde, PI): A Prospectively Designed Study to Assess the Relationship between Tumor Mutation Burden and Predicted Neo-antigen Burden in Patients with Advanced Melanoma or Bladder Cancer Treated with Nivolumab or Nivolumab plus Ipilimumab (CA209-260)
A Prospectively Designed Study to Assess the Relationship between Tumor Mutation Burden and Predicted Neo-antigen Burden in Patients with Advanced Melanoma or Bladder Cancer Treated with Nivolumab or Nivolumab plus Ipilimumab (CA209-260) Background and rationale: Please refer to section 3.0 of the Protocol Study design: This is a prospectively designed, open label study. It includes 2 independent study populations (melanoma and bladder) Study population and sample size: Patients with histologically confirmed locally advanced or metastatic disease of the following tumor types who meet the eligibility criteria: 1. melanoma and 2. bladder cancer. 120 evaluable patients will be enrolled in two separate arms. In each arm, 60 evaluable patients will be enrolled. Major study interventions: All eligible patients with melanoma will receive ipilimumab at a dose of 3mg/kg combined with nivolumab at a dose of 1mg/kg. The ipilimumab and nivolumab will be dosed every 3 weeks for 4 doses. Thereafter, patients may be eligible to receive nivolumab monotherapy at a dose of 3mg/kg administered every 2 weeks for up to 2 years. All eligible patients with bladder cancer will receive nivolumab at a dose of 3mg/kg administered every 2 weeks for up to 2 years. Patients with bladder cancer who have confirmed disease progression after treatment with nivolumab monotherapy may be treated with the combination of nivolumab and ipilimumab. Main outcome measures/analyses: Please refer to section 2.0 of the Protocol
IRB No. 01-127H-2 (Dr. Jayesh Kamath, PI): Signalosome-oriented Phosphotyrosine Profiling of B-cell Malignancies
Study description not available
IRB No. 17-045-2 (Dr. Mario Perez, PI): The Airway Inflammatory Profile of E-Cigarette Users
Study objective: The research study is about how the human body, particularly the airways, react to the regular use of e-cigarettes. The purpose is to show that regular use of e-cigarettes can be associated with airway inflammation in the sputum of regular users of e-cig. We intend to study if the regular use of e-cig, in a simliar way to conventional cigarettes, can trigger an inflammatory response in the airways. Hypotheses: 1. subjects who use e-cigarettes have evidence of airway inflammation when compared to healthy non-smoker subjects 2. Subjects who smoke regular tobacco cigarettes have evidence of more airway inflammation than e-cigarette users. 3. Subjects who use e-cigs with flavoring, e.g. chocolate, or regular cigarettes with flavoring (e.g. menthol) will have more airway inflammation than e-cig and regular cigarette users who don't use flavored products, e.g. menthol. Aims: 1. We plan to characterize airway inflammation profile in e-cig users compared to healthy non-smokers 2. We plan to characterize the airway inlfammatory profile of tobacco cigarette smokers compared to e-cig users. 3. We plan to characterize the effect of menthol in e-cigarettes and tobacco cigarettes on the airway inflammatory profile.
IRB No. 14-041HO-1 (Dr. Rajesh Lalla, PI): Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients (ORARAD)
The ORARAD study is a prospective cohort study to document dental and other oral outcomes in patients who receive radiation therapy as part of treatment for a head and neck cancer. Seven hundred and fifty-six participants will be enrolled nationally over a three year period. Of these, 135 will be enrolled at UCHC. All participants will be seen for the study before starting radiation therapy then at six-month intervals for up to two years after the start of radiation therapy. The primary outcome will be the two-year rate of tooth loss after radiation therapy. Secondary outcomes will include measures of dental caries, periodontal health, salivary flow, and exposed bone/osteoradionecrosis.
IRB No. 17-021S-1 (Dr. Richard Fortinsky, PI): Care Management for Cognitively Vulnerable Older Adults
The purpose of the study is to compare ways to support the health of people over age 65 who may be experiencing signs of memory problems, feelings of sadness, or feelings of confusion. The study will look at how nurses, social workers and other health care professionals can help older adults get the care they need and to stay as healthy as possible. This type of support provided by these healthcare professionals is called "care management services". The study will compare two different care management teams: "Home Based Care Team" and "Telephone Based Care Team". The "Home Based Care Team" (HBCT) is composed of a nurse practitioner who is specifically trained to provide care and psychosocial support to older adults, social worker, physical and occupational therapists, registered dietician, pharmacist and community health educator. The Home Based Care Team nurse practitioner will lead this care management team. Interaction with the team will primarily take place within the older adult's home. The "Telephone Based Care Team" (TBCT) is composed of a nurse care manager who will assess the older adult's current health status and provide referrals to other healthcare professionals as needed. Interaction with the "Telephone Based Care Team" will primarily take place over the phone.
IRB No. 15-073-3.2 (Dr. Agnes Kim, PI): Circulating Biomarkers and Noninvasive Cardiac Imaging Techniques That predict Cancer Therapy Cardiotoxicity
The primary goal of this pilot study is to identify early signs of cardiotoxicity in patients with a wide range of cancers who are treated with anthracycline chemotherapy, alone or in conjunction with other chemotherapeutic or molecularly targeted cancer drugs, before there is irreversible cardiac dysfunction or clinical heart failure. We hypothesize that an elevation in apoptotic and inflammatory biomarkers and early changes in myocardial deformation as measured by strain imaging after exposure to anthracycline chemotherapy predict future development of cardiac dysfunction. By checking the levels of these biomarkers before chemotherapy, then at 3 months and at one year in cancer patients receiving anthracyclines, our goal is to determine whether those patients with a ""spike"" in level develop left ventricular dysfunction and/or clinical heart failure. Similarly, strain imaging by echocardiography will be performed at baseline, then every 3 months and at one year. We hypothesize that a decrease in global longitudinal strain can predict future reduction in LVEF. Our goal is to identify early those patients who are at a high risk for anthracycline-related cardiac toxicity. Early identification may lead to early institution of cardioprotective therapies (i.e. beta blockers and ACE inhibitors), which may prevent irreversible cardiac dysfunction and clinical congestive heart failure. Objectives: To determine the potential utility of biomarkers for the early identification of patients with cancer who are at risk for cardiac dysfunction. To determine whether biomarker levels, or serial changes in biomarker levels, or combination of biomarkers (activated caspase-3, troponin I, IL-6, TNF alpha, CRP, caspase-1, BNP) could predict subsequent cardiotoxicity in patients treated with anthracycline chemotherapy. To determine the utility of strain imaging in the identification of early cardiotoxicity. To determine whether cleaved caspase-3 and caspase-1 show serial changes over time during the course of cancer treatment with chemotherapy. Hypotheses: A serial increase in biomarker levels from baseline to post-chemotherapy may predict subsequent development of systolic or diastolic cardiac dysfunction. Caspase-3 as an apoptotic marker, caspase-1 as an inflammatory marker upstream of IL-1beta, IL-6 and CRP, and troponin I as cardiac injury marker can be quantified in human circulation. An elevation in the levels of these markers may indicate anthracycline-related cardiac apoptosis/ injury and associated inflammation. Strain imaging by echocardiography can identify early sub-clinical imaging evidence of cardiotoxicity. Taken together, the advanced strain imaging and novel biomarkers may identify those who are at risk of developing clinical cardiac dysfunction or heart failure. In the future, we will test whether prevention of overt heart failure can be achieved by institution of medications such as beta blocker and angiotensin converting enzyme inhibitor or angiotensin receptor blocker in these at-risk individuals.
IRB No. 17-013-6 (Dr. Susan Tannenbaum, PI): Retrospective study to investigate clinical utility of BIOARRAY Therapeutics genomic panel as a predictor of pathological response in breast cancer patients treated with taxane-based neoadjuvant chemotherapy as well as in patients who have developed metastatic disease.
In our study we are partnering with BIOARRAY Therapeutics. It is a biotechnology company that has developed a genomic profiling test based algorithm. This algorithm can predict response in breast cancer patients when treated with taxane-based chemotherapy. This information can help physicians personalize treatments upfront. The goal of this study is to validate using retrospective samples, the ability to predict response based on their BIOARRAY test profile.
IRB No. 15-164S-3.2 (Dr. Julie Wagner, PI): Diabetes Risk Reduction through Eat,Walk,Sleep And Medication Therapy Management for Depressed Cambodians (DREAM)
Diabetes Risk Reduction through Eat, Walk, Sleep And Medication Therapy Management for Depressed Cambodians (DREAM) This project is designed to reduce risk for diabetes in Cambodian Americans with depression. 210 Cambodian Americans in southern New England will be screened for their diabetes risk as well as depression; those at risk for diabetes with depression will be enrolled. This study will determine the effect of Lifestyle Modification vs Lifestyle + Medication Therapy Management (MTM) vs Supportive Services Control. Assessments gather data such as sleep, activity, anthropometrics, mental health symptoms, and medications at baseline, 1year and 2years. Blood tests will be performed on the same schedule for glucose, insulin, and inflammation. Hair samples will be obtained on the same schedule for levels of cortisol Cambodian Americans have been previously studied by these Investigators who found that found 50% of this group (over age 35) have 5 or more chronic diseases including heart attack, chronic depression and/ or PTSD. Their rates of diseases like diabetes, hypertension and high cholesterol are twice those of national averages. Overall Cambodian health status in the US is worse than other Asian refugee groups resettled in the US from their refugee camps. The Diabetes Prevention Program (DPP) has shown that disease onset can be delayed or even prevented by lifestyle modification programs such as that to be provided here. The KHA agency is a partner with the National Diabetes Education Program and committed to overcoming care barriers which underserved communities face. Such programs help mitigate depression by activating and engaging their clients. This PI & Team will utilize Community Health Workers (CHW) to conduct the research and deliver the lifestyle program called Eat, Walk, Sleep. 1/3 of the subjects will receive EWS which has been specifically tailored for the unique language and cultural considerations in this group.The PI has previously done a similar diabetes education intervention with non english speaking Latinos with low literacy- delivered in an ethnic agency setting by CHWs, including home and group participation. For 1/3, EWS is combined with secure pharmacist (Medication Therapy Management-MTM) videoconferencing interactions at home. 1/3 (70 subjects) 1/3 will receive control/Supportive Services Group- will receive Enhanced Standard CHW support/services referral, while undergoing the same initial evaluation assessments . The researchers seek to determine that lifestyle intervention will produce greater improvement in risk factiors and that biologic factors-waist size,blood pressure, diabetes marker- HgBA1c, and others are improved.
IRB No. 18-082-2 (Dr. Erin Mead-Morse, PI): Early Mobilization After Thumb (Carpometacarpal) Arthroplasty
The purpose of this research study is to determine the best post-operative therapy after a thumb (carpometacarpal or CMC) arthroplasty. Patients are currently placed in a thumb splint for 4 weeks after their thumb surgery. However, new research has questioned whether 4 weeks of splinting is needed. Our study will compare patients'; outcomes between 2 groups. One group will be placed in a splint for approximately 10 days after surgery and the other group will be in a splint for the normal duration after surgery (about 4 weeks).
IRB No. 17-155-3 (Dr. Adam Lindsay, PI): Fundamentals of Orthopaedic Surgery (FORS) & Fundamentals of Arthroscopic Techniques (FAST) Surgical Simulators
The purpose of this research study is to evaluate two surgical simulators as a way of assessing and improving surgical skills. The simulators are composed of materials founds at hardware stores such as PVC pipes, pipe insulation, foam bricks and wood blocks. Participants will be asked to perform different surgical skills such as suturing, drilling and/or arthroscopy using one or both of the simulators while being observed. Participation involves multiple 20-30 minute testing sessions to evaluate surgical skills over time. The following individuals are invited to participate in this study: • All UConn Medical Students • All UConn Medical Residents • All UConn Medical Fellows • Attending Physicians that perform more than 5 orthopaedic surgery/arthroscopic operations per month
IRB No. 16-211-3.1 (Dr. Matthew Costello, PI): Individualized Assessment and Treatment Program for Alcoholism: Treatment and Mechanisms
Through our 2009 R-21 pilot project we developed a cellphone-based experience sampling (ES) procedure that assesses, in near real time, coping skills and associated thoughts and feelings that contribute to preventing relapse in alcoholics in treatment. We propose using the experience sampling procedure prior to treatment to collect data on thoughts, feelings and behaviors that patients have when they encounter drinking situations in real life. This information will be used by a therapist tailoring an individualized cognitive-behavioral treatment for each particular patient. The individualized assessment and treatment program (IATP) will be compared to a more conventional packaged cognitive-behavioral treatment (PCBT), and to a Case Management Control condition (CaseM). 207 men and women meeting criteria for alcohol use disorder will be randomly assigned to 12 weekly sessions of either CaseM, PCBT or IATP. Follow-ups will be conducted at posttreatment, and at 3-month intervals out to 27 months. The use of momentary assessments of thoughts, feelings and behaviors will allow us to determine what patients are actually doing, in close to real time, to initiate and maintain their own sobriety. The use of experience sampling in the follow-up period will allow us to determine whether the mechanisms that were active in initiation and early maintenance continue to be active in maintaining long-term abstinence. By comparing IATP with CaseM and PCBT we will be able to control for the general effects of study participation (i.e., "common factors"), the effects of being in a treatment study and receiving manualized treatment, general skills training (psychoeducation), and therapist presence.
IRB No. 13-087-3.2 (Dr. Susan Tannenbaum, PI): Factors Influencing Fatigue in Breast Cancer Patients Undergoing Breast Irradiation
Study description not available
IRB No. 11-009-3.2 (Dr. Molly Brewer, PI): GOG 212 A Randomized Phase III of Maintenance Chemotherapy Comparing 12 Monthly Cycles of Single Agent Paclitaxel or CT-2103 VS No Treatment Until Documented Relapse in Women with Advanced Ovarian, Primary Peritoneal or Fallopian Tube Cancer Who Achieve a Complete Clinical Response to Primary Platinum/Taxane Chemotherapy
Study description not available
IRB No. 12-013S-3.2 (Dr. Biree Andemariam, PI): Biomechanical Properties of Blood Cells in Sickle Cell Disease
Study description not available
IRB No. 18-167-2 (Dr. Agnes Kim, PI): Assessment of Cardiac Abnormalities in Sickle Cell Patients Using Echocardiography
Assessment of Cardiac Abnormalities in Sickle Cell Patients Using Echocardiography
IRB No. 18-170-1 (Dr. Sara Tabtabai, PI): Evaluation of a Guideline Directed Medication Titration (GDMT) Program in Patients with Heart Failure with Reduced Ejection Fraction
A patient newly diagnosed with heart failure with reduced ejection fraction requires close follow up for titration of medications as blood pressure, electrolytes and symptoms permit. Although the benefits of guideline directed medical therapy (GDMT) have been well studied, there remains a significant gap in the receipt of GDMT in the ambulatory and hospitalized setting. As such, we seek to assess the utility of focused GDMT clinic to reduce this gap. We hypothesize that implementation of a GDMT focused clinic will reduce the gap, improve medication compliance and in turn, improve the mean ejection fraction, and reduce hospitalization rates.
IRB No. 18-228-2 (Dr. Agnes Kim, PI): Assessment of Myocardial Deformation in Adult Patients with Type 2 Diabetes Mellitus
This retrospective case-control study aims to determine if patients with early-stage diabetic cardiomyopathy have subtle myocardial deformation usingspeckletracking echocardiogram. The two aims of the study are (1)to determine whether adult diabetic patients with preserved left ventricular ejection fraction have abnormalities in myocardial deformation and (2) to determine whether adult diabetic patients have impaired diastolic function as assessed by traditional methods as well as by novel method, i.e. left atrial strain, a measurement that has been shown to correlate with pulmonary capillary wedge pressure.
IRB No. 19-036-1 (Dr. Jun Lu, PI): Rheumatology-Dermatology Combined Clinic Patient Registry
The Rheumatology-Dermatology Combined Clinic Patient Registry is a prospective registry that collects patient data within the UConn Department of Dermatology combined clinic for patients being treated for both rheumatologic and dermatologic conditions. Both dermatologists and rheumatologists participate in care for patients suffering from connective tissue disease with both cutaneous and rheumatological manifestations. By establishing combined rheumatology-dermatology clinic, patients will receive collaborative care from both specialties in the same visit. The combined multidisciplinary clinic offers the opportunity for improving care quality, patient satisfaction, and continued education and professional development for physicians. The protocol includes patients over the age of 18 that are being treated in the UConn combined rheumatology-dermatology clinic. This registry will gather data over a 10 year period for future research regarding improving patient care, diagnosis, treatment and long term outcomes for this subspecialty clinic.
IRB No. 19-105-1 (Dr. Sara Tabtabai, PI): Guideline Directed Medication Titration Program in Patients with Heart Failure with reduced Ejection Fraction
A patient newly diagnosed with heart failure with reduced ejection fraction requires close follow up for titration of medications as blood pressure, electrolytes and symptoms permit. Although the benefits of guideline directed medical therapy (GDMT) have been well studied, there remains a significant gap in the receipt of GDMT in the ambulatory and hospitalized setting. As such, we seek to assess the utility of focused GDMT clinic to reduce this gap. We hypothesize that implementation of a GDMT focused clinic will reduce the gap, improve medication compliance and in turn, improve the mean ejection fraction, and reduce hospitalization rates.
IRB No. 18X-148-2 (Dr. Kai Chen, PI): Sleep Apnea and Diastolic Dysfunction (SADD) Study
Obstructive sleep apnea (OSA) is strongly associated with a number of cardiovascular diseases including hypertension, atrial fibrillation, coronary artery disease, and heart failure. Hypothesis: Obstructive sleep apnea is linked to diastolic heart failure as evident by echocardiographic evidence of diastolic dysfunction. Aims of this study are (1) to determine whether OSA is associated with diastolic dysfunction by comparing the echocardiographic parameters between the subjects with abnormal sleep study and those with normal sleep study;(2) to determine if the severity of OSA as evaulated by the sleep study is associated with the degree of diastolic dysfunction; (3) to determine whether left atrial strain imaging as a part of diastolic dysfunction parameters closely correlates to the severity of OSA.
IRB No. 18-091S-1 (Dr. Erin Mead-Morse, PI): Addictive Potential of Little Cigars/Cigarillos in Dual Users: Effect by Flavor and Gender
This study aims to measure the potential for addiction to little cigars and cigarillos (LCCs) compared to cigarettes, determine their substitutability for cigarettes, and whether flavor adds to their addictiveness. We will also explore differences by sex. The focus of the study is on young adults who currently smoke both cigarettes and LCCs. This is a randomized cross-over study with 125 young adult (18-34 years old) dual users (50% women, 50% men) who are not interested in quitting. Participants will be in the study for two weeks. For the first week, they will be randomized to receive either their preferred flavor of LCC or unflavored (plain tobacco) LCCs (of the same brand). They will be asked to use the study-provided LCC in place of their usual LCC as much as they are able to for one week. Then they will cross over and receive the other type of LCC and use that for one week. We will compare measures of dependence and use for flavored vs. unflavored LCCs vs. cigarettes. We will also differences between men and women in their addiction to LCCs.
IRB No. 19-147-2 (Dr. Jonathan Covault, PI): Dutasteride treatment for reducing heavy drinking in AUD: Predictors of efficacy.
Heavy drinking remains a significant public health problem and is frequently under treated. Although several medications have been shown to help patients stop or reduce drinking, additional medication options are needed as there is considerable variability in effectiveness or tolerability of existing medications for individual patients. Additionally, identification of individual subject level predictors of efficacy are needed to better personalize pharmacotherapy treatment recommendations. This 24-week treatment study will use an innovative randomized placebo controlled step therapy design to examine the safety and efficacy of dutasteride to reduce drinking among a sample of 190 treatment seeking women and men with hazardous levels of alcohol use. At 12-weeks placebo non-responders will transition to dutasteride and dutasteride non-responders will transition to naltrexone, an FDA approved medication with demonstrated efficacy for reducing heavy drinking. 12-week responders (reduction in drinks/week of 60% or greater compared with screening) will continue for an additional 12-weeks on their initial study medication assignment (dutasteride or placebo).
IRB No. 19-214-1 (Dr. David Steffens, PI): Apathy and Reward Systems in Alzheimer's Disease
Apathy is a common feature of Alzheimer's disease (AD) that is related to functional decline, but its underlying neurobiology is poorly understood. In this application, we propose to use functional magnetic imaging and tasks that focus on the brain's reward system to examine apathy in AD and in late-life depression. Our aim is to identify new targets for intervention to improve apathy in patients with AD.
IRB No. 19-206S-1 (Dr. Cato Laurencin, PI): Just Us Moving Program in the State of Connecticut (JUMP-CT)
JUMP-CT aims to increase light physical activity and reduce weight in the African and Hispanic American populations with type 2 diabetes in the greater Hartford region. This program is a simple behavioral modification program focused on decreasing the hemoglobin A1c levels, a marker of blood sugar levels,in diabetics and in turn improving the management of diabetes and its associated complications and risk factors over time.
IRB No. 13-061C-6.2 (Dr. Biree Andemariam, PI): CASIRE Sickle Cell Renal Disease Cohort International Study Protocol
Study design: This study's design is cross-sectional. Our cross-sectional study approach will allow us to determine particular age cohorts (young children, adolescents and young adults) that might be at risk for developing early renal dysfunction. Further, it will also allow us to determine which estimates of GFR have the best correlation to the changes in renal function. Specifically, we will determine if estimates in GFR, increasing microalbuminuria, or blood pressure changes will be predictive of early renal dysfunction. Study procedures: The research staff, which includes study coordinators from UCHC and CCMC, co-investigators from CCMC, and a principal investigator from UCHC, will only enroll subjects with sickle cell disease who are at steady state and have not had an infection, pain crisis, emergency room visit or hospitalization within two weeks of the time that they are enrolled in the study. Subjects will be screened by the PI or co-investigators, with whom they have a treating relationship. Potential subjects will be told about the study by the PI or co-investigators during a routine clinical visit. Those potential subjects who verbalize interest in learning more about the study will then have an opportunity to discuss the study further with a member of the research staff. If the subject then verbalizes desire to participate, informed consent will be obtained. The questionnaire will then be administered in its entirety by a member of the research staff by verbally asking the subject to answer each question. If there is any uncertainty about the answer to a particular question, the medical chart will be reviewed for verification. We estimate it will take about 20-30 minutes for the subjects to fill out the questionnaire with a research staff member. The subject's involvement ends once the questionnaire is completed.
IRB No. 14-056SF-6.1 (Dr. Pamela Taxel, PI): Investigation of the Ability of the UCONNS (University of Connecticut OsteoNecrosis Numerical Scale) to Predict the Risk for the Developing Osteonecrosis of the Jaw in Patients Receiving Bone-Modifying Therapies for Cancer
The purpose of this proposal is to investigate the risk factors for osteonecrosis of the jaw (ONJ), a known complication of several bone-modifying therapies used in the treatment of advanced cancers. When this complication occurs, it can lead to the discontinuation of important therapy that often impacts the quality of life in skeletal-related events in this population. With the use of a weighted scale that we have devised, the University of Connecticut OsteoNecrosis Numerical Scale (UCONNS), based on known risk factors for ONJ, we aim to validate this scale as a potential predictor of patients at risk, so they may be appropriately monitored and preventative treatment can be initiated. As the medical community has limited guidelines regarding ONJ, we anticipate that this scale, if validated, will foster better communication among providers, as well as improve patient outcomes. This proposal represents a unique collaboration between two investigators in the dental and medical schools at the University of Connecticut Health Center. We hypothesize that the UCONNS can aid in the identification of cancer patients who may be at increased risk for the development of ONJ associated with the use of bisphosphonates and the newer bone modifying therapy, denosumab.
IRB No. 14-057SF-6.1 (Dr. Pamela Taxel, PI): Investigation of the Ability of the UCONNS (University of Connecticut OsteoNecrosis Numerical Scale) to Predict the Risk for the Developing Osteonecrosis of the Jaw in Women Receiving Bone-Modifying Therapies for Breast Cancer
The aim of this proprosal is to investigate the risk factors for Osteonecrosis of the Jaws (ONJ), a known complication of several bone-modifying therapies including bisphosphonates and denosumab, a human monoclonal antibody. ONJ is most commonly seen with the use of these medications in the treatment of skeletal related events in cancer patients with metastatic bone disease, and less frequently seen in the treatment of osteoporosis. This complication often causes significant effects on quality of life that may lead to the discontinuation of important disease-modifying therapy. We have recently developed the UCONNS (University of Connecticut OsteoNecrosis Scale) a weighted scale based on known medical and dental risk factors for ONJ that we are currently validating both retrospectively and prospectively for use as a potential predictor of patients at risk, so they may be appropriately monitored and preventative treatment can be initiated. The current proposal aims to add to the UCONNS by prospectively measuring serum bone markers that may prove valuable in predicting patients that are at increased risk for developing ONJ. We will follow patients who are being treated with bone modifying agents in order to prospectively measure and evaluate a panel of unique parameters of bone metabolism to identify potentially predictive serum biomarkers for the development of ONJ. We hypothesize that the UCONNS can aid in the identification of breast cancer patients who may be at increased risk for the development of ONJ associated with the use of bisphosphonates and the newer bone modifying therapy, denosumab.
IRB No. 14-107CS-6.2 (Dr. Biree Andemariam, PI): Identification of Patient-specific RBC-endothelial Cell Adhesion Profiles as Markers of Sickle Cell Disease Severity.
The research objective of this proposal is to determine in 25 adult/pediatric SCD patients (1) the relationship between pain severity phenotype and the strength of adhesion between single red blood cells (RBCs) and single endothelial cells (ECs) isolated from peripheral blood and (2) the ex vivo effect of pharmacologic inhibitors on RBC-EC adhesion, creating both a patient-specific adhesion profile and therapeutic signature. The results are expected to lead to novel individually-targeted approaches to inhibit the onset and limit the duration of painful vaso-occlusive episodes (VOEs). Our central hypothesis is that the strength of adhesion between RBCs and ECs at baseline is related to patient-specific pain severity phenotype, resulting in the need for patient-specific drug therapy. To test the hypothesis, we will pursue the following three specific aims: Investigate the relationship between pain severity phenotype and baseline RBC-EC adhesion profile in SCD subjects -- We will measure the strength of adhesion between single RBCs-ECs from SCD subjects at baseline. Baseline/steady-state adhesion profiles will be compared on an inter-patient level to determine which adhesion profiles correlate most highly with pain severity phenotype. Assess the association of VOE severity with changes in RBC-EC adhesion from baseline to VOE onset. We will measure the change in strength of adhesion between single RBCs-ECs from baseline to VOE onset. Changes in adhesion will be compared on an inter-patient level to determine whether relative changes in adhesion profile at VOE onset correlate with VOE severity. Test the ex vivo effect of targeted pharmacotherapy on the RBC-EC adhesion profile of SCD subjects -- We will measure (at baseline and at VOE onset) the ex vivo inhibitory effect of two known RBC-EC adhesion blockers (propranolol and abciximab) to identify patient-specific anti-adhesive therapeutic signatures.
IRB No. 14-136CS-6.2 (Dr. Biree Andemariam, PI): Hemoglobinopathies and Bone Health
This research study has two purposes. The first purpose is to determine whether having sickle cell trait is a risk factor for the development of bone thinning at an earlier age than expected. Nearly 10% of African Americans carry sickle cell trait and most of them are unaware of it. African Americans are less likely to develop thin bones than whites, but if they sustain a bone fracture, they are more likely to die from it. We believe having sickle cell trait may lead to bone thinning and predispose a subset of African Americans to dangerously thin bones. The second purpose is to try to understand why individuals with sickle cell disease have thinner bones than healthy individuals do. Doctors have already discovered that people with sickle cell disease have very thin bones, but they have not determined why. Our study will try to identify whether the bone thinning is from the body not making enough bone or from the body losing bone once it is made.
IRB No. 17-193C-6.2 (Dr. Biree Andemariam, PI): Measures of Functional Ability in Adults with Sickle Cell Disease
This study is a prospective, clinical/translational research pilot study using a web-based, daily survey. Pain in adults with sickle cell disease (SCD) is unique in that patients often experience acute and chronic pain simultaneously. Numerical rating scales are often unhelpful in the measurement of this type of pain as patients tend to report high pain scores despite noted variations in functional ability. This pattern of functional improvement with continued report of high pain intensity scores is common in patients with recurrent and chronic pain. A functional assessment tool that can reflect functional changes over brief time periods (days) is necessary to 1) allow for the examination of the impact of acute pain on usual function, 2) investigate the extent to which acute pain symptoms create a burden for patients and caretakers, 3) use as an outcome measure that would allow for objective measurement of changes in functioning as the result of acute pain interventions, and 4) study individual differences in functioning within specific patient groups. We have previously developed the YAPFAQ, a measure of acute functional ability in youth with sickle cell disease. No tool for measurement of daily functional ability in adults with SCD exists. The aim of this project is to provide preliminary data on item content for an adult acute functional ability tool, while examining the impact of other variables such as pain, mood and sleep on daily function in individuals with SCD. We propose to complete a pilot study of 40 adults between the ages of 21-40 years with SCD. Each adult will access an online survey daily for 30 days to report 20-30 items regarding their functional ability, sleep, mood and pain. Participants will access the daily survey through any standard web-browser using REDCap and complete the survey between 6pm-10pm each day.
IRB No. 14-221-3.2 (Dr. Glenn Konopaske, PI): Two-implant supported maxillary overdentures: Clinical and patient reported outcomes.
PROJECT SUMMARY Maxillary overdentures supported by four implants have clearly shown to be effective and provide improved function as compared to conventional dentures, particularly when alveolar ridges are resorbed and when palate form is shallow. This preliminary, descriptive study aims to prospectively study the efficacy of only 2 implants to support maxillary complete dentures. The specific aims of this study are: 1) To generate an estimate of three-year implant and prosthesis success for two implant-retained maxillary complete denture prostheses; and 2) To better understand patient reported outcomes across time. Upon IRB approval and patient recruitment into the trial using pre-determined inclusion and exclusion criteria, 20 maxillary edentulous patients will be provided with two implants to support their existing denture. Each patient will receive two dental implants bilaterallly in the maxillary anterior region at the lateral incisor/canine regions. After successful osseointegration, two "Locator" abutments will be inserted over the implants and the patient's existing denture will be attached to the abutments through a laboratory reline of the denture and thus converted to a two-implant retained maxillary overdenture. Thereafter follow-up exams will be performed and clinical outcomes and patient-reported outcomes will be studied at baseline (conventional complete dentures); 1 week post-insertion of relined maxillary overdenture; 6-months; 1 year post-insertion; 2 years post-insertion; and 3 years post-insertion (all two-implant supported maxillary overdenture). The clinical outcomes will be recorded in a descriptive manner for variables including implant survival, surgical complications, radiographic bone levels, plaque index/bleeding index around the implants, prosthetic complication, wear or loosening of the abutments, replacement of the nylon inserts and other descriptive variables. The patient-reported outcomes will be recorded at follow-up appointments using a visual analog scale (VAS) and a modified oral health impact profile (OHIP-14). Additional follow-ups as required by each patient for any adverse outcomes related to treatment will also be documented. Those variables that allow comparison to conventional denture will be compared using statistical measures. SPECIFIC AIMS This descriptive, patient based study is designed to determine implant survival for dental implants and the success of implant retained complete removable prostheses when only two implants are utilized. It is well known that there is a projected increase in the number of edentulous patients in the United States. It is also known that maxillary edentulism is more common than mandibular edentulism. While the general standard of care for complete tooth replacement in the maxillary arch is the "conventional" complete denture, it is well established that maxillary implant overdenture supported by four implants generally outperforms the conventional denture. The objective of this study is to determine whether placement of a minimal number (2) of implants supporting a maxillary overdenture can result in good implant / prosthesis survival and satisfactory patient satisfaction and quality of life. Positive results from this pilot study can be used to generate hypotheses supporting a larger clinical study that may have an impact in re-defining the minimal intervention necessary for rehabilitation of the edentulous maxilla. We plan to accomplish our objectives by the pursuing the following two specific aims: To generate an estimate of three-year implant and prosthesis success for two-implant retained maxillary complete denture prostheses. The clinical outcomes will be recorded in a descriptive manner for variables including implant survival, surgical complications, radiographic bone levels, plaque index/bleeding index around the implant.
IRB No. 18-050-1 (Dr. Jun Lu, PI): Corrona Psoriasis Registry
The Corrona Psoriasis Registry is a prospective, multicenter, observational registry that will compare the safety of approved psoriasis therapies in patients across the nation who are actively being treated with these medications by dermatologists. Patients must have been started on, or have been switched to a biologic psoriasis medication within the 12 months preceeding enrollment. Adverse events of special interest, including malignancy, will be followed for all patients.
IRB No. 19-121JS-1 (Dr. Daniel Rosenberg, PI): Ellagic Acid, Urolithins and Colonic Microbial Communities Affected by Walnut Consumption
The purpose of this study is to investigate whether adding walnuts to your diet can have a beneficial effect on your colon. Walnuts contain a natural compound called ellagitannin that is broken down in the stomach to ellagic acid. Ellagic acid is further broken down by your gut microbiota into a group of polyphenolic compounds called urolithins that have powerful anti-inflammatory actions. The gut microbiota is defined as the community of bacteria, fungi, viruses, etc. that live in your gut. Increasing evidence suggests that polyphenol consumption is associated with lower risk of colorectal cancer. We aim to investigate how a person's gut microbiome may contribute to your ability to form these powerful antioxidant urolithin compounds. Antioxidants are a group of substances that have the ability to reduce inflammation. In this study, we will collect demographic information and dietary records, and perform tests on proteins, DNA and/or RNA from samples of colon biopsies, blood, stool and urine to investigate how a person's microbiome may contribute to their ability to form urolithins.
IRB No. 17-180H-6.2 (Dr. Susan Tannenbaum, PI): Electronic Cigarette Use During Pregnancy HHC-2017-0208
An observational, longitudinal, prospective cohort study of 375 women (125 women who smoke conventional cigarettes exclusively during pregnancy, 125 who use e-cigs and 125 dual users). Background: Maternal smoking is one of the most important modifiable causes of poor pregnancy outcomes in the United States causing 16% low birth weight babies, 6% of premature deliveries, and 6% of preterm related deaths. Quitting smoking is the best option to improve maternal and child health, and smoking reduction is also beneficial. However, an increasing number of pregnant smokers may be using electronic cigarettes (e-cigs) as a substitute for or in conjunction with cigarette smoking. Rationale for this study: E-cigs are an emerging public health issue. They may have a net benefit or risk. A need exists to evaluate the impact of e-cigs in vulnerable populations such as pregnant women. The information about the potential risks and benefits is needed to adequately inform pregnant women and health care providers who counsel their patients. Study Design: This is an observational, longitudinal, prospective cohort study. Study Population and Sample Size: Pregnant smokers who exclusively smoke conventional cigarettes, or who use e-cigs. A total of 375 subjects (125 who smoke conventional cigarettes and 125 who use e-cigs, and 125 dual users) will be enrolled across six sites (UCHC, HH, Baystate Medical Center, University of Colorado, Denver Health, and University of East Tennessee). Major Study Interventions: Not a treatment study. Observational only. Providing written smoking cessation education materials and referral to state Quitline if needed. Main Outcome Measures/Analyses: To determine if e-cigarettes use leads to lower exposure to toxicants in pregnant women relative to those pregnant smokers who smoke conventional cigarettes. Hypotheses, aims and objectives: Hypothesis 1: We hypothesize that women who smoke conventional cigarettes will have higher urine NNAL and serum cotinine & benzene levels compared to users of e-cigs (dual users or exclusive users). Aims / objectives 1: To compare the overall toxicant exposure in pregnant women who use e-cigs to women who smoke conventional cigarettes Hypothesis 2: We hypothesize that infants born to women who smoke conventional cigarettes will have higher levels of NNAL, benzene/SPMA and cotinine compared to infants born to users of e-cigs (dual or exclusive users). Aim/Objective 2: To compare toxicant exposure and birth outcomes among infants born to pregnant women who use e-cigs compared to women who smoke conventional cigarettes Hypothesis 3: We hypothesize that maternal urine for NNAL will be predictive of birth weight, and that this effect will be mediated by inflammatory processes, measured using markers of inflammation [high sensitivity C-reactive protein (hs CRP) and intercellular adhesion molecule (ICAM-1)]. Any additional effect of benzene/SPMA will be explored. Aim/Objective 3: To explore potential mechanisms by which toxicants could influence birth weight.
IRB No. 19-148-2 (Dr. Susan Tannenbaum, PI): An Open-label Extension Study of IMR-687 in Adult Patients with Sickle Cell Anemia (Homozygous HbSS or Sickle-ß0 Thalassemia) Who Participated in Study IMR-SCD-102
Study Title:An Open-label Extension Study of IMR-687 in Adult Patients with Sickle Cell Anemia (Homozygous HbSS or Sickle-B0 Thalassemia) Who Participated in Study IMR-SCD-102 Background: With a neonatal incidence of 294,000 to 330,000 patients worldwide (Piel 2013), SCA is a rare inherited disorder of red blood cells (RBCs) that is both serious and life threatening. The most common manifestations of SCA include vaso-occlusive crisis, chronic and acute severe pain, acute chest syndrome, stroke, priapism, acute anemia (particularly from aplastic crisis and splenic sequestration), increased susceptibility to infection, and progressive damage to major organs including the spleen, brain, kidney, heart, lung, skin, retina, vestibular cochlear systems, and bone. In developed countries where there is prenatal Screening and wide spread access to prophylactic and acute interventions, the median age of death remains in the 40s to 50s though many patients succumb to the disease much earlier (Platt 1994; Lanzkron 2013; Paulukonis 2016). Rationale for the study:Study IMR-SCD-102-EXT is an extension of Study IMR-SCD-102. During the extension, IMR687 100 mg will be administered orally once daily. Since Study IMR-SCD-102 is the first study in patients with SCA, an extension will provide long-term safety and tolerability data for these subjects. In addition, long-term pharamcodynamic (PD) and efficacy data will be collected. Study design: Patients are eligible for this open-label extension study immediately following the End-of-Study visit for Study IMR-SCD-102 (i.e., approximately 30 days after the last dose of study drug in the Phase 2a study). Following screening assessments to determine continued eligibility, patients will be enrolled into this extension study. IMR687 100 mg will be administered orally once daily. Patients will return to the study site for visits at week 1, and months 1, 4, 8, and 12 during the first year. Thereafter, patients will return to the study site every 6 months during years 2, 3, and 4. Telephone-based check-ins may be performed on weeks where there are no scheduled assessments or in the event of lack of patient availability for an in-person visit. Safety and concomitant medications will be monitored throughout the study; PD and clinical outcome measures will be performed at selected site visits. Study sample size:Approximately 70 patients currently participating in Study IMR-SCD-102 are expected to be eligible for this long-term extension. Major study intervention:The dose of IMR-687 to be administered in this extensions study is 100 mg per day as a single oral dose. This is the optimum dose expected being tested in the Phase 2a study and is considered to have positive pharmacodynamic effect, based on preclinical modelling and exposures in the FIH study of IMR-687 in healthy volunteers.Pending emerging data from Study IMR-SCD-102, the dose of IMR-687 may be adjusted in this study as appropriate. Main outcome measures/analyses: Primary objectives: To assess the long-term safety and tolerability of IMR-687 in adult patients with sickle cell anemia (SCA), defined as homozygous sickle hemoglobin (HbSS) or sickle-B0 thalassemia, who were previously enrolled in Study IMR-SCD-102. Exploratory objectives: To assess the pharmacodynamic (PD) effects of IMR-687 in adult patients with SCA who were previously enrolled in Study IMR-SCD-102. To assess the potential efficacy of IMR-687 on SCA-related clinical outcome measures in adult patients with SCA who were previously enrolled in Study IMR-SCD-102.
IRB No. 20-035-1 (Dr. Matthew Imperioli, PI): The provision of video information effect on the level of pain perception during electrodiagnostic studies: a randomized controlled trial
This study is to assess whether video information can ease patient's anxiety and pain in EMG/Nerve conduction study that were tranditionally thought to be painful compared to written information. We simply use questionaire and survery as the only intervention
IRB No. 20-084-2 (Dr. Zhichao Fan, PI): Mechanisms and Roles of Integrin Activation of Human Blood Leukocytes
Background, Rationale and Significance: Integrins are key mediators of the recruitment of leukocytes which play critical roles in human immunity and inflammatory diseases. Insights about Integrin function hold out the prospect improved inflammatory disease prevention. Blood leukocytes including neutrophils, monocytes, and lymphocytes, all have a recruitment cascade during inflammation and infections. They can first roll on the vascular endothelium, firmly adhere (arrest) on the vascular endothelium, spread on the vascular endothelium, perform intravascular crawling, transmigrate through vascular endothelium, and finally, migrate to the site of inflammation or infections. This cascade is essential for the recruitment and immunological function of leukocytes and involved in many infectious and inflammatory diseases. Integrins, are a group of adhesion molecules vital for the recruitment cascade. Studying the mechanisms and roles of integrin activation will bring new insights into leukocyte recruitment and immune functions and invite discovery of novel treatments for infectious and inflammatory diseases. (See Protocol-Appendix for Leukocyte Recruitment, Integrin Activation Pathways and Super Resolution/ Flow Imaging Graphics- pg.10-16) This protocol is used to develop a continuing supply of fresh blood donations for the Integrin Research Laboratories under the direction of the PI @ UConn Health, Dept of Immunology where the PI recently joined. 2 recent PI authored publications are included for reviewer, explanatory of the Integrin research for which materials are to be utilized in ongoing experiments.
IRB No. 10-273S-2 (Dr. Robert Clark, PI): The Role of Unique Lipids Derived From Common Human Bacteria in Multiple Sclerosis
Study description not available
IRB No. 14-193CH-6.2 (Dr. Damion Grasso, PI): Prenatal Exposure to Stress
The purpose of the repository is to build a research program focused on epigenetic influences of early childhood exposure to violence and disruption in the development of the stress response system. The work will continue the focus on the glucocorticoid receptor gene FKBP5 and it's companion molecules in the stress response pathway.
IRB No. 18-038-1 (Dr. Biree Andemariam, PI): Intergenerational Transmission of Trauma-Related Risk
Evidence suggests that the effects of trauma exposure, including posttraumatic stress disorder (PTSD), can be transmitted across generations to shape pathways to psychological impairment in offspring; however, the mechanisms and timing of these effects are not well known. The purpose of this study is to better understand these mechanisms. It builds on an ongoing study to examine associations between maternal PTSD during pregnancy, newborn infant epigenetic patterns, and infant stress reactivity at 6 months of age, in the context of the caregiving environment. Hispanic/Latino participants who had enrolled in the ongoing study and who have agreed to be contacted and invited to participate in future research opportunities will be invited to participate. Specific aims are to examine (1) associations between maternal PTSD and epigenetic patterns in both mothers and newborn infants, (2) links between maternal PTSD during pregnancy, maternal and newborn epigenetic patterns, and biological and behavioral indicators of stress reactivity in 6-month-old infant offspring, and (3) whether aspects of the caregiving environment moderate the effects of maternal PTSD and epigenetic patterns on infant stress reactivity.
IRB No. 19-145J-2 (Dr. Danielle Luciano, PI): Cellular Phenotyping of Endometriosis – Towards Biomarker Discovery and a Mechanistic Understanding of Disease
Endometriosis is a common gynecological disorder that results when tissue that normally lines the inside of a woman';s uterus - the endometrium - grows outside the uterus. The tissue forms large lesions that most typically implant in the ovaries, fallopian tubes and the tissue lining the pelvis, causing severe and debilitating pain, fatigue and infertility. The condition can only be diagnosed through surgical removal of lesions and treatment is aimed primarily at managing the pain symptoms. Removal of endometriosis lesions offers temporary relief, but lesions and their associated symptoms frequently recur in patients. There is no cure. Endometriosis is a significant health and economic burden owing to disability and lost productivity among women. A major reason why we lack options for diagnosing and treating endometriosis is because our understanding of the fundamental mechanisms of disease remains poor. Understanding the cell types and cell-type-specific gene expression patterns in the lesion and the surrounding environment is a foundational step that will inform hypotheses on the etiology and pathogenesis of disease and reveal the molecular factors that could represent viable targets for diagnostic and therapeutic development. We hypothesize that the local environment creates conditions for endometriotic lesions to develop and invade surrounding organs, and that both the lesion and lesion-adjacent tissues contain factors that could represent viable targets for biomarker-based diagnostics and therapeutics. To investigate our hypothesis, we will employ cutting-edge technologies for investigating the gene-expression patterns of single cells, and for high-resolution imaging to understand how different cell types comprising a tissue are spatially arranged. We will perform these experiments in human endometriotic lesions from the pelvic cavity, in tissue immediately adjacent to the lesion (to begin to understand the molecular features of the local environment), and in healthy endometrial tissue. We will use computational algorithms to compare the different gene expression patterns and to correlate these patterns with specific cell types. We will then analyze the spatial arrangement of these cell types to understand the cell-cell interactions that could help lesions to establish and grow. This work will yield the first, comprehensive profile of the endometriosis ";ecosystem"; along with a list of expressed genes that researchers can use to form new hypotheses about disease etiology. This list of expressed genes will likely contain molecular factors that could be developed into biomarkers or therapeutic targets.
IRB No. 20-122-1 (Dr. Lihong Wang, PI): A Neural Study of the Maturational Shift in Emotion Regulation in Healthy Aging and Depression
This study will focus on examining the impacts of age and depression history on emotion regulation, both behaviorally and neurally. Maladaptive emotion regulation in older subjects with a history of depression is a risk for depression relapse. Confirming the failure in the normal adult maturational shift in emotion regulation in remitted depressed patients and identifying neural mechanisms supporting emotion regulation strategies used in remitted depressed subjects will inform the future development of novel prevention or treatment interventions.
IRB No. 20-137-1 (Dr. Sejal Thacker, PI): A PILOT RCT STUDY COMPARING DIMENSIONAL ALTERATIONS AFTER SOCKET GRAFTING WITH XENOGRAFT VERSUS ALLOGRAFT
6.1 MASTER LAY SUMMARY STUDY TITLE - A Pilot RCT Study comparing dimensional alterations after socket grafting with xenograft versus allograft BACKGROUND - After extraction of a tooth the healing socket goes through a remodeling process in which there is a substantial dimensional loss of bone volume. Various bone graft materials have been used to minimize this bone volume loss and facilitate future dental implant placement. This study is to test the differences between two bone grafting materials - a xenograft and an allograft. Both grafting materials are extensively and routinely used and are considered standard of care. AIM - The aim of the study is to compare the xenograft and allograft biomaterial when used in extraction sockets to minimize dimensional changes. The comparison between the two materials will be done using a 3-dimensional scan and by doing intraoperative measurements. The performance of the graft will also be compared from a histological standpoint. HYPOTHESIS - The null hypothesis is there is no difference in the performance of the two biomaterials with respect to dimensional changes after 6 months of healing. PRIMARY OBJECTIVE - Horizontal and vertical dimensional changes of extraction sockets as evaluated in a 3 dimensional radiograph (CBCT scan) pre-extraction and 6 months post extraction when grafted with xenograft versus allograft. SECONDARY OBJECTIVE - Horizontal and vertical dimensional changes of extraction sockets as evaluated intraoperatively in patients mouth pre-extraction and 6 months post extraction when grafted with xenograft versus allograft. Histological difference in the healing of the graft particles. A biopsy of the site will be done at 6 months and the core will be used for histological analysis Amount of newly regenerated bone will be evaluated using a micro CT analysis. The biopsy cores used for histology will be used for this purpose as well.
IRB No. 20-105-2 (Dr. Kevin Manning, PI): Apathy and Biomarkers of Cognitive Decline in Depression Study
This research is being done to determine if older adults who are experiencing depression and/or apathy (decreased motivation) are at increased risk of developing cognitive decline and Alzheimer';s disease. The purpose of this research study is to try and find a better way to diagnosis cognitive decline and/or Alzheimer';s disease in older adults. Diagnosing Alzheimer';s disease or cognitive decline is complex. With no single test currently available, diagnosis is based on an individual';s history, physical examination, and cognitive testing. With the information gathered from a lumbar puncture (or spinal tap) and subsequent analysis of the fluid obtained from the procedure, we may improve our ability to detect brain changes associated with Alzheimer';s disease well before a person begins to experience significant cognitive decline (or dementia).
IRB No. 20-123-1 (Dr. David FitzGerald, PI): Child Clinic Registry
The objective of this project is to develop a data registry. A registry collects, processes, stores and distributes data for future scientific investigation. The registry will consist of medical record information obtained from patients treated at Child and Adolescent Psychiatry Outpatient Clinic at UConn Health. The treatment in this clinic is focused on addressing psychological and psychiatric behaviors.
IRB No. 20-186-1 (Dr. Biree Andemariam, PI): SARS-CoV-2 Serosurveillance in Health Care Workers on COVID-19 patients
Infection with SARS-CoV-2 causes human COVID-19 (HCoV-19). Health care workers are at risk of being exposed to this virus. Since majority of COVID19 patients have been asymptomatic or mildly symptomatic, it is important to identify those who have been exposed, converted to sero-positivity and acquired potential immunity. Finding of seroconversion among healthcare workers will help understand the epidemiology of this infection in the healthcare setting and potentially better inform the workers and their associates
IRB No. 20-192-2.F (Dr. Bruce Liang, PI): A randomized, open-label study of the vascular and microbiologic efficacy of dipyridamole plus standard care vs. standard care in hospitalized COVID19 patients.
Infection with SARS-CoV-2 causes human COVID-19 (HCoV-19). In severe illness, COVID 19 infection results in lymphopenia, elevated D-dimer levels, hypercoagulation, hypertension, acute respiratory distress syndrome (ARDS), and acute cardiac injury. Dipyridamole (DIP) is an FDA- approved drug which inhibits adenosine uptake that leads to increased extracellular adenosine which in turn stimulates adenosine receptor mediated vasodilatory, anti-platelet and anti-inflammatory effects. These effects are also augmented by DIP's inhibition of phosphodiesterase. In addition, DIP appears to bind to the HCoV-19 protease enzyme and also suppresses HCoV-19 proliferation in Vero E6 cells with an IC50 less than or equal to 100 nM. Plasma concentrations in humans from routine dosing regimens (regimen of 50 mg three times per day) exceed this IC50 value for the duration of the dosing interval. In vivo anti-viral effect for DIP, very recently has been demonstrated in vesicular stomatitis virus-induced pneumonia with prolongation of survival (1). There is limited clinical data on dipyridamole in COVID-19 patients. At this writing, the remdesivir and hydroxychloroquine are now approved for investigations, by the FDA to treat these patients. Although the exact mechanism by which these drugs may work in this infection is not known, DIP exerts its potential salutary effect via different mechanism. In a preliminary, un-randomized trial with a small number of COVID19 patients treated with prophylactic anticoagulation therapy (Hubei China, January 2020) --the addition of DIP led to increased platelet and lymphocyte counts with reduced D-dimer level, compared to standard of care patients (1). Additionally, 2 weeks after DIP treatment of 12 patients, 3 of the severe cases and all 4 of the mild-to-moderate cases were discharged from the hospital. One patient died while 3 remaining patients were in remission in the hospital. In the control group, 3 of the 3 mild-to-moderate cases and 1 of 4 severe cases were discharged and only 1 was in remission in the severe group with 1 death. However, the trial was not randomized and was small in size, hence there was no statistical analysis for clinical outcomes. 100 will be enrolled with in an open label, randomized controlled trial with 50 being randomized to receive dipyridamole, 100 mg tid for 7 days being added to Standard Care. (1). Therapeutic effects of dipyridamole on COVID-19 patients with coagulation dysfunction Xiaoyan Liu, Zhou, Hai-Bin Luo, et. al doi: https://doi.org/10.1101/2020.02.27.20027557
IRB No. 20-230-2 (Dr. George Kuchel, PI): Prestin as a Biomarker for Hearing Loss in Cisplatin Therapy
Cisplatin is a widely used and effective chemotherapeutic agent but well-known for also causing hearing loss or ototoxicity. However, there is currently no available blood-based biomarker test to evaluate the onset of ototoxicity in patients undergoing cisplatin. Diagnostic blood tests are easy to obtain and non-invasive and can provide critical information for treatment, intervention, and even prevention of downstream pathology. Several animal studies have shown outer hair cell electromotility protein prestin to be a promising biomarker for ototoxicity, however it has yet to be applied in human studies. Our hypothesis is that prestin may present as a measurable and specific serological biomarker for early detection of ototoxicity secondary to cisplatin chemotherapy. Our specific aim is to determine a temporal relationship between prestin levels and cisplatin treatment.
IRB No. 20-210S-1 (Dr. Matthew Imperioli, PI): The Feasibility and Effectiveness of an Opioid Package Prototype (OPP) to Impact Opioid Prescribing, Dispensing, and Patient Use Outcomes
This study is looking at how the packaging of opioid medication affects the use of opioids following surgery. The study is comparing opioid use when provided in a standard amber vial (normal orange bottle) versus a blister pack called the Opioid Package Prototype, or “OPP” for short. Study participants will receive their post-surgery opioid medication from Arrow Pharmacy (located in the Outpatient Pavillion) in one of the two packages, which are pre-assigned. Participants will also complete surveys and/or interviews before surgery and at 1 week, 1 month and 3 months after surgery. Basic criteria to participate include being an adult having one of 17 common surgical procedures by a participating orthopaedic surgeon and using opioid medication for post-operative pain.
IRB No. 21-070J-1 (Dr. Matthew Imperioli, PI): Dynamic assessment of immune system in COVID-19 patients: Flu Vaccine Pilot Study 1
This prospective, single-site pilot study is designed to determine the feasibility to recruit and enroll COVID-19 convalescent adults into a study that will assess immunity changes associated with aging. To complete a 12 subject pilot study with the following aims: To establish feasibility of conducting a larger trial with the enrollment of COVID-19 convalescent adults, we will enroll 6 older (65 years and older) and 6 young (25-50 years) adults that have recovered from COVID-19. To gather preliminary data on epigenomic signatures of responsiveness to the seasonal influenza vaccine in adults recovered from COVID-19. To gather preliminary data on microbiome signatures of COVID-19 sequelae. The objective of this project is to systematically identify the most relevant factors that are associated with the prolonged effects of COVID-19 on immunity by applying a systems immunology approach that incorporates high-resolution immunologic assays with state-of-the-art genomic, proteomic, metabolomic assays. Major questions we will address include: i) which immune cell types and gene expression programs are remodeled with COVID-19 in the long term?; ii) do these immune alterations associate with changes in vaccine responsiveness?; iii) do COVID-19 sequelae differ between older and younger adults, and between men and women?; iv) are there multi-omics biomarkers of reduced immunity due to COVID-19? To answer these questions, we will establish a longitudinal cohort of young (25-50 yrs old) and older adults (≥65 yrs) who recovered from COVID-19 and we will characterize their immune systems in detail under baseline and upon influenza vaccination.
IRB No. 20-072-1 (Dr. Fiona Campbell-Furlong, PI): Study of The Relationship Between 27-Hydroxycholesterol Levels and Hematopoietic Stem Cell Mobilization in Pregnant Women
Study Title: The Relationship Between 27-Hydroxycholesterol Levels and Hematopoietic Stem Cell Mobilization in Pregnant Women SPECIFIC AIMS The specific aims of this project are: To investigate the association between plasma 27-hydroxycholesterol (27HC) and total cholesterol levels during pregnancy progression. To investigate the association between plasma 27HC levels and mobilized hematopoietic stem cell (HSC) number during pregnancy progression. To investigate whether 27HC levels in the peripheral blood differ between pregnant and non-pregnant women. To investigate whether mobilized HSC number in the peripheral blood differ between pregnant and non-pregnant women. To investigate the association between CYP27A1 gene expression/mutation and complications during pregnancy. 4 STUDY DESIGN This prospective, single-site, observational study will enroll 50 healthy adult females in their first trimester of pregnancy and 13 adult healthy non-pregnant female controls. The purpose of this research study is to investigate the relationship between plasma 27HC levels and HSC mobilization during pregnancy. Participants will provide 6 mL of blood samples for the analyses of 27HC levels and HSC number at each research visit (single visit for non-pregnant female controls and 5 visits every 8-10 weeks for pregnant participants). Permission will also be obtained from the pregnant participants for the collection of placental and umbilical cord tissue discarded after delivery. 4.1 Characteristics of the Study Population Cohort A Number: 50 Age Range 18-40 years Sex: Females Health Status: Healthy, in their first trimester pregnancy Duration of Participation: 5 study visits every 8-10 weeks coinciding with routine prenatal visits, hospitalization for labor and delivery, and post-natal visit. First visit approximately 30 minutes in duration and the remaining 4 visits 10 minutes each. Placental tissue and umbilical cord specimens (surgical discard) will be collected following labor and delivery. Cohort B Number: 13 Age Range 18-40 years Sex: Females Health Status: Healthy, not-pregnant Duration of Participation: Single research visit, approximately 30 minutes in duration. 4.2 Sampling Plan The study sample will be drawn from healthy pregnant women and healthy non-pregnant women in the catchment area of UConn Health in Farmington, CT under the direction of Dr. Winston Campbell. 5 SELECTION AND ENROLLMENT OF PARTICIPANTS Fifty (50) healthy pregnant women and 13 healthy non-pregnant women, ages 18-40 years, from all ethnic and racial groups will be recruited in this study. Dr. Winston Campbell, the Principal Investigator of the clinical protocol, and his clinical team will recruit for this study from the patient population of UConn Health. All pregnant women presenting to the Department of Obstetrics and Gynecology at UConn Health in their first trimester for prenatal care will be considered candidates to participate in the study (Cohort A). Healthy controls (Cohort B) will be recruited from the patient population presenting in the Gynecology clinic. The UConn Health Women';s Center evaluates approximately 2,000 patients annually for routine gynecological care and the John Dempsey Hospital accounts for about 1,000 deliveries annually. Recruitment in this study will occur via direct clinician referral of the potential participant to the study team. Any recruitment material used will be presented to the IRB for approval before use. Vulnerable Populations Fifty (50) healthy adult females in their first trimester of pregnancy will be enrolled as part of this study. All five study visits will coincide with routine pre-natal and post-natal visits. Six milliliters (6 mL) of blood will be collected at each of the five visits by experienced and trained staff (a total of 30ml over 32-40 weeks). Permission will also be obtained to collect discarded placental tissue after delivery. The study imposes no greater than minimal risk to the pregnant women and fetuses. The researchers will not interfere/influence the standard of care, nor will they have any part in: 1) any decisions as to the timing, method, or procedures used to terminate a pregnancy, and 2) determining the viability of the fetus at the termination of the pregnancy. No other vulnerable populations will be enrolled in this study. Collaborating Sites/Investigators All prospective recruitment, enrollment, and clinical data abstraction will occur at UConn Health by Dr. Christine Nkemeh and the other Maternal-Fetal Medicine fellows under the direction of Dr. Winston Campbell, Professor, Dept. of Obstetrics and Gynecology, UConn Health. The blood sample collection, processing, and complete blood count, will be performed at the UConn Health - Department of Pathology & Laboratory Medicine. Plasma preparation and flow-cytometric analyses of coded blood samples will be performed at the UConn Health - Dept. of Cell Biology. Lipid panel and bile acid analyses will be performed at the UConn Metabolic Phenotyping Facility. The code key will be maintained at UConn Health with access restricted to Dr. Campbell and the UConn Health study team. Coded and deidentified plasma samples will be shared by Dr. Oguro with Dr. Jeffrey G. McDonald, Assoc. Prof., Center for Human Nutrition, University of Texas Southwestern Medical Center (UTSW) for analysis of plasma 27HC levels. 5.1 Eligibility Criteria Eligibility Criteria for Cohort A- Pregnant Females (n=50) Inclusion Criteria: Female Age 18-40 years Pregnant <12 weeks of gestation Receiving prenatal care at UConn Health Able and willing to provide written informed consent Willing to provide placental tissue following delivery Exclusion Criteria: <18 years old Hypercholesterolemia Known history of any of the following conditions: Malignancy (eligible if no recurrence in the last 5 years) Congestive Heart Failure Cardiovascular Disease (unstable ≤ 6 months) Kidney disease Renal failure Impaired hepatic function Diabetes HIV, AIDS or other Immunodeficiency Autoimmune disease such as: Rheumatoid Arthritis, Inflammatory Bowel Disease, Systemic Lupus Erythematosus, etc. Currently taking any prescribed medication more than 3 times a week for longer than 2 weeks (other than pregnancy related vitamins or supplements) Recent (≤ 3 months) trauma or surgery Current substance and/or alcohol abuse Prisoners Eligibility Criteria for Cohort B- Healthy Controls (n=13) Inclusion Criteria: Female Age 18-40 years Not Pregnant (confirmed with Urine Pregnancy Test) Able and willing to provide written informed consent Exclusion Criteria: <18 years old Hypercholesterolemia Known history of any of the following conditions: Malignancy (eligible if no recurrence in the last 5 years) Congestive Heart Failure Cardiovascular Disease (unstable ≤ 6 months*) Kidney disease Renal failure Impaired hepatic function Diabetes HIV, AIDS or other Immunodeficiency Autoimmune disease such as: Rheumatoid Arthritis, Inflammatory Bowel Disease, Systemic Lupus Erythematosus, etc. Currently taking any prescribed medication more than 3 times a week for longer than 2 weeks (other than pregnancy related vitamins or supplements) Recent (≤ 3 months) trauma or surgery Current substance and/or alcohol abuse Prisoners 5.2 Study Enrollment Procedures Cohort A participants will be recruited from the population of pregnant women presenting at Department of Obstetrics and Gynecology for prenatal care. Cohort B participants will be recruited from the patient population presenting at the general gynecology clinic. A combination of IRB approved recruitment methods may be used; including, referral by clinicians, broadcast recruitment email messages, study flyers posted in public areas, clinics, and blood draw stations at UConn Health, video displays in clinics, etc. The majority of recruitment will occur via direct clinician referral of the potential participant to the study team. Dr. Campbell, or another UConn Health Dept. of Obstetrics and Gynecology clinician, will inform patient of the possibility of participating in a research study and ask if there is interest in learning more. If the patient is interested, the clinician or a Fellow will present the details of the study and administer the informed consent. If the patient prefers a separate visit for consent, this may be scheduled at their convenience. Interested patients will provide written consent following an informed consent discussion with an authorized member of the UConn Health study team prior to initiation of study activities. Since participants in Cohort A will receive ongoing prenatal care at the UConn Health Rheumatology clinic and study visits will be coordinated to coincide with routine prenatal/postnatal care visits and hospitalization for labor and delivery, a high rate of retention in this study is expected. Since participants in Cohort B will have a single study visit, a high rate of retention in this cohort is expected. 6 STUDY PROCEDURES 6.1 Schedule of Events Participants in Cohort A will have 5 study visits 8-10 weeks apart for a total study duration of up to 11 months. The study visits will coincide with their routine prenatal and postnatal care visits as follows: Visit 1: Coincides with the first prenatal visit (5-13weeks) Visit 2: Coincides with the prenatal visit for alpha-fetal protein analysis (17-24 weeks) Visit 3: Coincides with the prenatal visit for glucose tolerance test (28-32 weeks) Visit 4: At the time of admission into John Dempsey Hospital for labor and delivery Visit 5: Coincides with 4-6 weeks post-partum visit The researchers aim to collect blood specimens during each of the three trimesters, at the time of labor and delivery, and during their postpartum visit. Participants in Cohort B will have only one study visit. Event Cohort B Cohort A Visit 1 Visit 1 Visit 2 Visit 3 Visit 4 Visit 5 Informed Consent Prior to study activities x x Screening Form x x Medical History x x Demographics x x Current Medications x x Adverse Events x x x x x x Peripheral blood specimen (6 mL) x x x x x x Medical Notes on current pregnancy (from charts) x x x x x Medical Notes on outcome of pregnancy (from charts) x x Fresh placental tissue collection (following delivery) x Umbilical cord sample collection (following delivery) x 6.2 Description of Study Visits Visit 1: Approximate visit time = 30 minutes Consent Procedure Before any study activity, the IRB-approved Informed Consent Form (ICF) will be reviewed with the potential participant, section-by-section by a qualified member of the study team in a private area. Subjects will be given the opportunity to ask questions and to have them fully answered. Subjects who elect to enroll will sign and date the consent form. The member of the study team conducting the informed consent discussion will also sign and date the ICF. A copy of the ICF signed by the consenter and the subject will be provided to the subject. This process will be documented by the Documentation of Consent Form that will be stored in the research record under a unique Participant Identifier (PID). The original signed ICF will be stored separately from the research record and with other study documents that contain personal identifiers (HIPAA Authorization, or other). The HIPAA Authorization form will be provided to the participant to review and sign to authorize the use and disclosure of their Protected Health Information (PHI) collected for use in this study. We do not expect to encounter many non-English speaking patients in this study. However, in order to facilitate any non-English speaking patients who are unexpectedly encountered in the study, a short form consent will be made available as per the UConn Human Subjects Protection Program, Informed Consent - Short Form policy. This will only be presented to individuals who have a witness (who is fluent in English and the language of the subject) present and willing to translate for the patient. An IRB-approved Short Form consent document written in a language understandable to the subject, will be presented to the patient. The person obtaining consent will provide an oral presentation of the informed consent information to the subject and a copy of the IRB-approved consent form will be provided to the subject as a written summary. If the subjects consents to participating in the study, the subject will be asked to sign and date only the short form consent. The witness will sign both the short form consent as well as the IRB-approved informed consent form. The study consenter will only sign and date the IRB-approved informed consent form. A copy of the short form document as well as the IRB-approved informed consent form will be provided to the subject. If a larger non-English speaking population is encountered during the course of the study, the complete IRB-approved ICF will be translated into the language that this population understands. Enrollment The participant will be considered enrolled and will receive a unique participant identifier number (PID) number in the study once the ICF has been signed. The PID will not be derived from or include any direct personal identifiers (name, birthdate, medical record number, etc.). Screening After informed consent, participants will be screened for eligibility. For Cohort B participants, an on-site urine pregnancy test will be used to confirm non-pregnant status. Individuals that signed informed consent but do not meet all eligibility criteria will be withdrawn from participation and considered ";screen failures";. Data Collection Once all inclusion and exclusion criteria have been reviewed and the subject has been determined to have met all eligibility criteria, the following data collection forms (CRFs) will be completed: Demographic Information Form completed with subject by interview All the other data will be abstracted from medical charts by UConn Health IRB approved study team. Clinical data to be abstracted include: date of last menstrual period, expected date of delivery, gestational age at delivery, medical conditions, and medications will be obtained from the medical record. Infant information to be obtained from the medical record will include gestational age at delivery, date of delivery, mode of delivery, birth weight, 1 minute and 5 minute APGARS, and whether or not the baby is admitted to the NICU. Blood draw Blood (6 mL) will be collected peripherally following clinical care phlebotomy and blood draw by qualified clinical staff at UConn Health using best practices. Two EDTA (lavender top) Vacutainer tubes (6 mL) will be used for whole blood collection to obtain a total of 6 mL (3 mL in each tube). The research tubes will be labeled with sample ID (see Sample Processing, Labeling and Transfer) and date of collection. Once filled with blood, tubes will be immediately inverted 8-10 times to mix and ensure adequate anticoagulation of the specimen. The tubes will then be stored at 4°C until further processing at the UConn Health - Department of Pathology & Laboratory Medicine. The first EDTA tube (3 mL blood) will be used for complete blood count at UConn Health Dept. of Obstetrics and Gynecology and flow-cytometric analyses at Dept. of Cell Biology. The second EDTA tube (3 mL blood) will be used for plasma purification at Dept. of Cell Biology. The EDTA tubes will be stored on ice and securely transported to Dept. of Cell Biology for processing and analysis. Triple packaging consisting of a leak-proof primary receptacle (eg. blood tube), a leak-proof secondary package (eg. Sealable plastic bag), and an outer package clearly labeled with Biohazard sign will be used for secure transportation of the samples from Dept. of Obstetrics and Gynecology to Dept. of Cell Biology. At Dept. of Cell Biology, the plasma samples will be divided into 3 parts, labelled with sample ID (see Sample Processing, Labeling and Transfer) and date of collection. One part of the plasma sample will be shipped to UTSW (0.5 mL of plasma) for the analysis of plasma 27HC levels. Visits 2-5: Cohort A only - Approximate visit time = 10 minutes each Blood draw Blood (6 mL) will be collected peripherally by phlebotomy by qualified clinical staff at UConn Health using best practices at each study visit as detailed above. The blood draws at Visits 2, 3, and 4 will occur at the time of phlebotomy and blood draws performed for clinical care. Labelling, storage, processing, analysis, and transportation of samples to Dept. of Cell Biology will be as detailed above. Placental Tissue Collection Following delivery at the UConn John Dempsey Hospital, several samples of the placental tissue will be collected from the expelled placenta (to be discarded otherwise). Specifically, three 0.5cm3 blocks of placental tissue will be excised from the maternal side of the placenta. Collected specimens will be washed with sterile saline and placed into separate pre-labelled tubes (see Sample Processing, Labeling, and Transfer section) containing RNA stabilization reagent, DNA stabilization reagent, and fixative agent. All three pre-labelled tubes containing the reagents will be provided by Dept. of Cell Biology. The tubes will be stored on ice and securely transferred to Dept. of Cell Biology for processing and analysis. Umbilical Cord Sample Collection Following delivery of the placenta, a 1cm segment of the umbilical cord closest to the placental cord insertion site will be collected. This segment will be drained of all blood and then washed with saline. Collected specimen will be cut transversally into three pieces and placed into pre-labelled tubes (see Sample Processing, Labeling, and Transfersection) containing RNA stabilization reagent, DNA stabilization reagent, and fixative agent. All three pre-labelled tubes containing the reagents will be provided by Dept. of Cell Biology. The tubes will be stored on ice and securely transferred to Dept. of Cell Biology for processing and analysis. 6.3 Sample Processing, Labeling, and Transfer All specimens will be processed according to SOPs developed by the Dept. of Cell Biology team. Laminated copies of SOPs as well as labeling instructions will be provided to the UConn Health team prior to study initiation. All specimen tubes will be labeled with the sample ID and date of collection. The sample ID will be in the format 27HC-XXC-V#-S# where: 27HC is the study ID, XX is the two-digit sequential enrollment number and C is the cohort ";A"; or ";B";, V# is the visit number for blood samples (1, 2, 3, 4, or 5), S is the specimen type, and # is the tube number when multiple tubes of blood/placental tissue are collected (e.g., 27HC-01A-V1-B2, 27HC-01A-PM1, 27HC-04B-V1-P3). The Specimen type and tube number key is provided below: Specimen Type Description Tube Number B Blood- EDTA Tube 1, 2 PM Placenta-Maternal Side 1-3 U Umbilical cord 1-3 P Plasma 1-3 *Plasma separated from the blood in EDTA tube #2 The specimens will be prepared for transport using DOT/IATA compliant triple packaging consisting of a leak-proof primary receptacle (e.g. a closed tube), a leak-proof secondary package (e.g. sealable plastic bag), and an outer package clearly labeled with Biohazard sign (e.g. cardboard box or cooler). 6.4 Compensation There are no costs to study participants for taking part in the study. Participants in Cohort A will be provided a modest honorarium (total $20 for five visits: $10 gift cards at the end of visit 1 and $10 at visit 5). Participants in Cohort B will be provided a modest honorarium of $5 gift card. The gift cards will be presented directly to the participants by the study coordinator/fellow and the receipt will be documented. 6.5 Blood cell analysis Three (3) mL of fresh blood sample collected from participants (of the 6 mL) at each visit will be used for flow-cytometric analysis at Dept. of Cell Biology. Complete blood count will be performed at UConn Health either specifically for this study or as part of clinical care. The flow-cytometric analysis at Dept. of Cell Biology will evaluate the expression of CD34 and CD38 to obtain the frequency of HSCs that have CD34+CD38- cell-surface maker phenotype. 6.6 Plasma analysis The remaining three (3) mL of fresh blood samples collected from participants (of the 6 mL) will be processed at Dept. of Cell Biology for plasma purification. Purified plasma (~1.5 mL) will be divided into 3 tubes as follows: Tube #1: 500 uL for 27HC analysis (UTSW) Tube #2: 100 uL for lipid panel (UConn Metabolic Phenotyping Facility) Tube #3: Remaining volume (~900 uL) for storage for the backup (Dept. of Cell Biology) 6.7 Placental and umbilical cord tissue analysis The samples will be collected from 3 different loci from the maternal side of the placental tissue (a total of 3 pieces per tissue approximately 0.5 cm3 each) from pregnant women immediately after delivery at UConn John Dempsey Hospital. A 1cm section of umbilical cord will also be collected and cut transversely into three pieces. Specimens from the placenta and umbilical cord (one each) will be analyzed at Dept. of Cell Biology as follows: Piece #1: Place into a tube containing RNA stabilization reagent for mRNA expression analysis (mRNA expression analysis of CYP27A1 and other genes or RNA-sequencing at Dept. of Cell Biology) Piece #2: Place into a tube containing DNA stabilization reagent for genomic DNA mutation analysis (analysis of genomic mutations in CYP27A1 gene and other genes or whole genome sequencing at Dept. of Cell Biology) Piece #3: Place into a tube containing fixative reagent for immunohistochemistry (expression analysis of CYP27A1protein and other proteins at Dept. of Cell Biology) 7 RISKS AND PROTECTIONS 7.1 Potential Risks to Subjects Risk to Confidentiality: There is a potential risk to confidentiality due to the PHI that will be collected and stored in the subject';s research record. Risk from Blood draw: There may be a minor amount of discomfort due to the needle stick performed for the study blood draw. There is a minor risk of bruising (< 1%), infection at the phlebotomy site (< 1%) or dizziness following the blood draw (<1%). There is no additional risk to the participants from the additional low volume (6ml per visit) of blood drawn for this research. No more than 30ml of blood will be collected from the pregnant participants for purpose of this study over the approximately 40-week study period. No more than 6ml of blood will be collected from the participants in Cohort B. Risk from Placental and Umbilical cord specimens collection: The specimens collected for this study are placental and umbilical cord tissue that would otherwise be discarded. There is no additional risk to the participants in Cohort A or their new-born from the specimens collected for this research. 7.2 Adequacy of Protection against Risks The human subject components of this study will be conducted under the supervision of Dr. Campbell at UConn Health. UConn Health emergency care procedures will be followed if an adverse event or medical emergency occurs. The study site is located on the campus of a tertiary care hospital that is available for treatment of medical emergencies. Protection against Risk to Confidentiality All study visits will occur in a private area at UConn Health in Farmington, CT. Research records will be labeled with a participant ID (PID), an assigned unique identifier that is not derived from any patient identifiers. All contents of the research record will be labeled with the assigned PID. Research records will be stored in a secure area. A complete record of the subject's pertinent history and documentation of the visit will be kept on case report forms and will be stored in the research records. Research records will be accessible only to the IRB-approved UConn Health study team directly involved in conduct of the clinical protocol. Any study documents (Informed Consent Form, HIPAA Authorization) that contain the participant's name will be kept in a separate file apart from the research record and will be stored in a secure location. A master key that links participant names and PIDs will be maintained in a separate and secure location accessible only to the Site PI and approved UConn Health study team. At no time will this key or any identifiable information be provided to researchers at UConn Health Dept. of Cell Biology or UTSW. Samples will be labeled as per SOPs (see Sample Processing, Labeling, and Transfer) and will not contain any patient identifiers when they are transferred to Dept. of Cell Biology. Coded clinical data linked with study samples by the PID will be provided to the Dept. of Cell Biology study team for analysis. HIPAA personal identifiers will not be included in the clinical dataset/samples provided to Dept. of Cell Biology for use in analysis. The clinical data will be provided to Dept. of Cell Biology by secure file transfer or by the entering the data into a password-protected excel database. Dr. Oguro, as an investigator on the clinical protocol may be present at clinical team meetings when identifiable information is present. He will not record or disclose participant identifiers and will not receive the code key at any time. Publications and presentations about discoveries from the data generated from samples collected in this study will not identify subjects by name. Protection against Risk from Blood Draw Six (6) mL of blood will be drawn for participants at each research visit (five visits for Cohort A participants and one visit for Cohort B participants). Blood will be drawn by experienced, trained research staff in a clinic setting on a hospital campus. The site where the needle will be inserted will be wiped with alcohol before and after the draw. Only sterile needles will be used. An adhesive bandage will be placed over the site after the draw. Emergency treatment will be accessible on campus for any severe complications from blood draw. For participants in Cohort A, blood draws at visits 1, 2, 3, and 4 will follow phlebotomy and blood draws that are part of clinical care. Protection against Risk from Placental Specimen Collection Placental specimens will be collected following delivery by experienced, trained staff in appropriate settings. 7.3 Data and Safety Monitoring Data and Safety Monitoring Plan (DSMP) The Data & Safety Monitoring Plan for this study describes the components of the study that will be monitored by the study coordinators and consenters once annually. Recruitment, drop outs, unanticipated problems, data integrity and confidentiality, participant privacy and the general conduct of the study will be reviewed. Minutes of the annual DSMP review will be kept in the regulatory binder and provided to IRB at study continuation. Procedures in place to ensure confidentiality of research data are as follows: Only authorized individuals have access to any data, used or stored (via electronic format or as hard copy records). Only designated research staff and investigators will be granted access. All data collected on data forms are stored in a secure records room located in the Principle Investigator';s office at UConn Dept. of Ob/Gyn. CRF data and data abstracted from EMR will be entered into a excel database labeled only by the PID and the resulting dataset shared with Dr. Oguro at Dept. of Cell Biology. 8 BENEFIT Participants will not directly benefit from the information gathered in the study but other people may benefit in the future. Investigators in this study will gain insight into the mechanism of HSC mobilization. It is possible that findings from this study could lead to research projects to understand the mechanism of HSC mobilization during pregnancy as well as the relationship between gene mutation and complications, to prevent anemia during pregnancy, and to improve HSC mobilization methods for transplantation. There is also the possibility that no benefit will come from this study. 9 INTEGRATIVE DATA ANALYSIS 9.1 Power Calculations This study is part of a powered study with two study sites: UConn Health and Chinese University of Hong Kong (CUHK). To determine approximate sample sizes for this study, a literature review was performed to identify estimates of effect size and variability that could be extrapolated to this research study. All sample size calculations are based on two-sided tests with alpha=0.05, with a goal of achieving 80% power to detect the association of interest. For example, linear regression results from two publications were used to inform sample size estimates for Specific Aims 1 and 2. Karuna et al. reported a significant association between 27HC and total cholesterol in healthy controls (beta coefficient=0.08, r= 0.54); based on these estimates, a sample size of 26 subjects would provide 80% power to detect an association of this magnitude [12]. For Aim 2, examining the association between 27HC and HSC number, we used data provided by Cimato et al. who found a significant relationship between LDL cholesterol and CD34+ HSPC in human subjects taking statins (beta coefficient=175, R-squared = 0.09573), and we hypothesize a similar relationship will be identified between total cholesterol and 27HC by the third trimester of pregnancy [11]. Using these estimates, a sample size of 82 individuals provides 80% power to detect such an association. Related to Aim 3, Ordovas et al. demonstrated a 49% increase in total cholesterol during pregnancy (mean 182 ± 35 ml/dL in the non-pregnant group and 265 ± 56 ml/dL by 37 weeks'; gestation) [19]. To detect such a large difference in means using a t-test, only 9 subjects are needed in each group (pregnant and non-pregnant). For Aim 4, Gao et al. measured hematopoietic stem/progenitor cells in the peripheral blood of human subjects, and found significantly increased levels in individuals with low compared to normal HDL Assuming similar variability in our sample of healthy women, we expect to see a difference in mean HSC levels of at least a similar magnitude (difference in means=11, standard deviation=15) between pregnant women in the third trimester and non-pregnant women [20]. With 82 pregnant women, 25 non-pregnant women are needed to have 80% power to detect this difference. Overall, sample sizes of 82 pregnant women and 26 non-pregnant women should provide sufficient power to investigate each of the aims. Accounting for expected dropouts, the study proposes to enroll 100 pregnant women and 26 non-pregnant women. Participants will be recruited at two study sites as follows: UConn Health: 50 pregnant women and 13 non-pregnant women CUHK: 50 pregnant women and 13 non-pregnant women The clinical study protocol at both sites will be reviewed by the respective institutional IRBs. 9.2 Statistical Analyses In addition to the hypothesis testing described above, descriptive analyses (mean, standard deviation, median and quartiles) will be performed to summarize 27HC, total cholesterol, and HSC number levels at each time point, and trajectories of their values over pregnancy progression will be plotted. The demographic characteristics of each cohort will be described. 10 DATA COLLECTION AND MANAGEMENT Data Collected from Human Subjects Specifically for Research Purposes Demographic information, medical history, date of last menstrual period, and current medication use will be provided by participants prior to the collection of blood at the research visit 1. Scanned copy of the CRFs redacted of PHI will be shared with the research team at Dept. of Cell Biology. The following medical data about current pregnancy (Cohort A only) will be abstracted from medical records into the study CRF: Gravida, Para, Abortion Date of Last Menstrual Period Expected Date of Delivery Gestational age Singleton pregnancy/Multiple pregnancy Ultrasound date and abnormal findings, if any Presence of any comorbidities (Preeclampsia, gestational diabetes, etc) Pregnancy Outcome- gestational age at delivery, date of delivery, mode of delivery Infant information- birth weight, 1 minute and 5 minute APGARS, and whether or not the baby is admitted to the NICU Participant Identification (PID) number A unique participant identifier (PID) not derived from any patient identifiers will be assigned to each participant once written informed consent for study participation has been obtained. The PID will consist of the study ID, ";27HC";, followed by two-digit sequential enrollment number and cohort (A-pregnant or B-non-pregnant); for e.g. 27HC-01A. Participant names or other personal identifiers will not be included in the study data set; all data will be identified only by PID. Access to individually identifiable private information about human subjects Access to identifiable study data will be restricted to the UConn Health study team involved in the conduct of the clinical protocol. Research records containing identifiable private information will be stored at the UConn Health and will only be accessed by IRB approved research coordinators/fellows. Coded clinical data will be provided to the Dept. of Cell Biology study team for analysis linked with study samples by the PID. The key linking the PID to participant identifiers will be stored separately and securely from the research records at the UConn Health Dept. of Obstetrics and Gynecology and will be accessible only to Site PI. The code key will not be provided to the Dept. of Cell Biology investigator or staff at any time. The Dept. of Cell Biology study team will have access to coded samples and data only. Dr. Oguro, as the Co-Investigator of this clinical protocol may be present at clinical team meetings when identifiable information is present. He will not record or disclose participant identifiers and he will not receive the code key at any time. Upon accessioning at Dept. of Cell Biology, the samples will be recoded and deidentified before being transferred to UTSW for 27HC analysis. Dr. Oguro will maintain the code key linking the UConn study PID and the new code assigned to samples shipped to UTSW for analysis. No genomic data generated in this study will be added to the participant';s medical record or returned to the UConn Health Dept. of Obstetrics and Gynecology study team. 10.1 Data Collection Forms (CRF) Forms to be labeled with the PID and completed for this study include: The Visit 1 Source Documentation Form The Visit 1 Source Documentation Form is labeled with the PID and includes the following data: Screening Form - This form lists all eligibility criteria. Participants must meet all inclusion criteria and not have any of the exclusion criteria to be enrolled into the study. Demographic Information Form-To be completed by participant Medical History and Medication Log Forms- Abstracted from EMR Clinical data abstracted from EMR Visits 2-5 (Cohort A only): Source Documentation Forms: The follow-up visit forms will document blood draws and the clinical data abstracted from EMR. Placental and umbilical specimens collection will also be documented. 10.2 Data Management Data Collection Forms (CRFs) will be labeled with the PID code and Visit Date and will be stored in the Research Record and/or electronically within the excel database. Paper CRF';s will be stored in a secure location in in the Principal Investigator';s office at the Obstetrics and Gynecology Clinic. Scans of completed CRFs, labelled only with PID, will be shared with Dept. of Cell Biology. Data from these scans will be entered into a password-protected excel database. Records will only be labeled with the PID and will not contain subject initials or any other identifier. 10.3 Quality Assurance Training A study initiation meeting will be attended by study staff in which the protocol, visit procedures, secure storage of research records, secure management of electronic databases and sharing of coded data with Dept. of Cell Biology, sample labeling protocol, and the process for sample transfer to Dept. of Cell Biology and UTSW will be reviewed. Delegation of Responsibilities A Delegation of Responsibilities log will be completed at the Initiation Visit for members of the CUHK study team that will be obtaining informed consent entering data on CRF, determining eligibility and labeling samples. This log will be kept in the study regulatory binder. 10.4 Protocol Deviations A cumulative Protocol Deviation Log will be kept electronically by the study coordinator with a copy added to the regulatory binder and provided to IRB at the next study continuation or closure submission, whichever occurs first. Deviations from the protocol will be entered on this log with a Note to File labeled with the PID and no personal identifiers added to the regulatory binder with a copy to the research record that describes the deviation, date when it was identified, the corrective action taken to prevent recurrence, whether or not the deviation met criteria of an Unanticipated Problem, and the date of IRB notification. Any unauthorized access to the database linking the research records to participant direct identifiers shall be reported to the IRB at the time that it is discovered as well as at annual review. Incidents of non-compliance, defined as any action that is taken or occurs that is not in accordance with an IRB approved study, IRB policies or regulations or failure to follow the requirements and determinations of the IRB, that is within the control of the study team must be reported to the IRB within 5 days of becoming aware of the occurrence. 10.5 Unanticipated Problems For the purpose of reporting Unanticipated Problems to IRB, internal adverse events that may also represent an unanticipated problem are defined as those events, experiences or outcomes that are: Unexpected (in terms of nature, severity or frequency) given (a) the research procedures that are described in the protocol-related documents, such as the IRB approved research protocol and informed consent document; and (b) the characteristics of the subject population being studied; and Related or possibly related to participation in the research (i.e., there is a reasonable possibility that the incident, experience, or outcome may have been caused by the procedures involved in the research). Any internal event meeting these criteria must be reported to the IRB, which will then make the final determination as to whether the research places subjects or others at a greater risk of harm (including physical, psychological, economic or social) than was previously recognized. 11 PARTICIPANT RIGHTS AND CONFIDENTIALITY 11.1 Institutional Review Board (IRB) Review This protocol, the recruitment material, the informed consent form, study CRFs, and any subsequent modifications will be reviewed and approved by the UConn Health IRB before use. 11.2 Informed Consent The informed consent process will begin after an individual confirms interest in participating in the study. A copy of the IRB approved Informed Consent Form (ICF) will be provided to the subject in advance for review, whenever possible. At the research visit, a study clinician will review the ICF, section by section, with the subject in a private room prior to any study procedures. Questions from the participant will be encouraged and will be fully answered. Once the form has been fully reviewed and all questions answered, the volunteer will be asked if they would like to participate in the study. If they agree to participate, they will be asked to sign and date the ICF indicating their consent. The consenter member of the study team obtaining consent will sign the ICF as well and a copy of the form signed by both the subject and the consenter will be provided to the subject. The Informed Consent process will be documented by the consenter on the Documentation of Informed Consent Form or as a note in the subject';s Medical record. Original signed and dated ICFs will be stored separately and securely away from the research record with other identifiable documents that contain participant identifiers. 11.3 Genomic Data Sharing Participants will provide consent within the ICF for sharing of genomic data generated from their samples in this study in publicly available online scientific databases in the future. Before this genomic data is shared, PIDs will be replaced with new codes and a link will not be kept between the data and participant identity. Even if a participant wants to withdraw from the study, genomic data once shared will not be withdrawn since there will be no way to link data with the subject. Subjects who decline consent for sharing of re-coded genomic data in public access databases will be enrolled in this study, however, their genomic data will not be shared in public access databases. Any samples remaining after study analysis has been completed will be kept in storage at Dept. of Cell Biology and will be given a new unique code. This random code will link the study information to the remaining sample. These recoded samples may be shared with other researchers and/or used in other projects. Subjects will provide or decline consent within ICF for sharing of samples for future research use. Subjects who grant permission for sharing of samples for future research use will not be contacted when the samples are used. 11.4 Withdrawal Subjects may withdraw their permission to participate in this study at any time by contacting: Dr. Winston Campbell Dept. of Obstetrics and Gynecology, UConn Health, 263 Farmington Avenue, Farmington, CT 06030 Phone: 860-679-7605, Email: wcampbell@uchc.edu Dr. Campbell will inform Dr. Oguro of the PID of the sample to be removed, but will not provide the subject';s name. The Dept. of Cell Biology team will locate and destroy/delete all specimens/data, linked to the subject requesting to be withdrawn. Any samples that were shared with UTSW before the request for withdrawal will be retrieved and destroyed. Any samples that were recoded (without a link to the PID) and recoded sequencing data shared in public access databases will not be withdrawn as there will be no way to link the recoded data/samples with the participant. 11.5 HIPAA Authorization Study participants must provide written authorization at study entry for use and disclosure of their Protected Health Information that is recorded and used in this study in order to participate. Participants may withdraw their Authorization at any time, but will then be withdrawn from the study. HIPAA Authorization will include access of UConn Maternal-Fetal Medicine fellows to identified data in the EMR for abstraction into the study CRF and database. Study data will be stored in a password-protected database coded by Participant ID (PID). The key linking PID and participant name will not be shared with Dr. Oguro and Dept. of Cell Biology team performing laboratory analysis. As a co-investigator, Dr. Oguro will be actively engaged in the conduct of this research and although he will not be provided with the key linking PID and identity of participants, he may have identifiable information disclosed to him during meetings with the clinical study team. Dr. Oguro will be listed in the HIPAA Authorization form for this reason.
IRB No. W19-209-1 (Dr. Rebecca Riba-Wolman, PI): A Long-Term Follow-up Study to Evaluate the Safety and Efficacy of Adeno-Associated Virus (AAV) Serotype 8 (AAV8)-Mediated Gene Transfer of Glucose-6-Phosphatase (G6Pase) in Adults with Glycogen Storage Disease Type Ia (GSDIa)
This study serves to continue to evaluate the safety and efficacy of the AAV8 Mediated Gene Therapy in those subjects infused with it in the 401GSDIa01 Study, this study is approximately 4 years in length. There are no investigative products given in this study.
IRB No. 21-074-2 (Dr. Jun Lu, PI): Corrona Atopic Dermatitis Registry: A Study of Post Approval Drug Safety and Effectiveness
The objective of the Corrona Atopic Dermatitis (AD) Registry is to create a national cohort of patients with atopic dermatitis. Data collected will be used to extensively evaluate the effectiveness and safety of medications used to treat atopic dermatitis. This will be done through the standardized collection of patient-reported outcomes (PRO) and clinician-reported outcomes (ClinRO), and the prevalence and incidence of comorbidities and adverse events, medication utilization patterns, and patient productivity measures.Personal information is also collected from each consenting registry patient allowing for linkages to other public or private clinical and administrative databases, as well as to databases maintained by organizations focused on the care and treatment of atopic dermatitis for the purposes of clinical, market, or outcomes research. This provides an opportunity to evaluate other aspects of the disease and its treatment including but not limited to clinical and drug cost-effectiveness, healthcare resource utilization, and patient adherence.
IRB No. 21-095J-2 (Dr. George Kuchel, PI): Dynamic assessment of immune system in COVID-19 patients Pilot Study 2: Aging and the Cutaneous Immune System in Young and Older Adults
This prospective, single-site pilot study is designed to determine the feasibility to recruit and enroll COVID-19 convalescent adults into a study that will assess immunity changes associated with aging. To complete a 8-subject pilot study with the following aims: To establish feasibility of conducting a larger trial with the enrollment of adults that have recovered from COVID-19 and healthy adults, we will enroll 4 younger adults (25-50 years) and 4 older adults (>65 years) and collect skin samples using punch biopsy and blood samples. To enumerate and assess functional status of dendritic cells, monocytes, macrophages, T cells and B cells in skin biopsies using multi-marker immunofluorescence and histo-cytometry (10+ markers) as well as image mass spectrometry (IMC) (30+ marker analysis in intact tissues). This is a prospective, single-site pilot study that will use an established and comprehensive approach to cellular and molecular analysis of non-dissociated tissues that will be applied herein to assess tissue immunity and changes associated with COVID-19 and aging. In this study, a total of 8 healthy adult participants who have either recovered from COVID-19 or have had no history of confirmed COVID-19 will be enrolled: four (4) older adults aged 65 years and older and four (4) younger adults aged 25-50 years. Participation in the study will involve two study visits scheduled on two consecutive days and up to three follow-ups via phone or email over three weeks after the biopsies. Subjects will be administered an intradermal injection of saline on one arm and two punch skin biopsies will be performed at the site of injection and adjacent the next day under local anesthesia. The biopsy sites will be closed with an absorbable suture. Peripheral blood specimens (50 mL each) will be collected at both study visits. Self-reported medical history, medication history and demographics information will be collected at Visit 1.
IRB No. 21-149J-1 (Dr. Matthew Imperioli, PI): High-resolution single cell profiling of SARS-CoV-2 vaccine responsiveness in healthy adults
This study is a collaboration between The Jackson Laboratory for Genomic Medicine (JAX) in Farmington, CT and UConn Health in Farmington, CT. All recruitment, enrollment, clinical data, and sample collection will occur at the UConn Center on Aging (COA) or at the Clinical Research Center (CRC), under the direction of Dr. George Kuchel, Professor of Medicine and Director of the UConn COA. This prospective, single-site, multi-cohort observational study is designed to determine how vaccine formulations and subject age affect immunologic responses to SARS-CoV-2 vaccine and to uncover the molecular signatures (genomics) elicited by novel COVID-19 vaccines. Up to 114 SARS-CoV-2 naïve healthy men and women aged 21 years or over, from all races and ethnic backgrounds that receive the Pfizer/Moderna/J&J COVID-19 vaccine will be enrolled to this study over a one-year period. Participation will involve nine (9) study visits for adults receiving the two-dose Pfizer or Moderna vaccine and seven (7) study visits for adults receiving the single-dose J&J vaccine. Blood samples (at all 9/7 visits) and nasal swabs (at three visits) will be collected.
IRB No. 20-190-1 (Dr. Jun Lu, PI): MICROBIOME OF THE SKIN IN INVERSE/GENITAL PSORIASIS
This research study aims to identify the microbiome (the genetic material of microrganisms) present in inverse/genital psoriasis sites and the oral site. This may help us understand what causes or worsens inverse/genital psoriasis. By identifying what causes/worsens psoriasis and the kind of microorganisms involved, we can begin to better understand the best way to prevent or treat these types of conditions.
IRB No. 21-167JS-1 (Dr. Daniel Rosenberg, PI): Microbiota, Metabolites and Colon Neoplasia
Dr. Daniel W. Rosenberg and his project Co-Investigators are conducting a research study called ";Microbiota, Metabolites, and Colon Neoplasia"; to examine whether eating walnuts can have a beneficial effect on the gut bacteria population and the tissue that lines the inside of the colon in healthy individuals. Background & Hypothesis The human diet can positively or negatively impact cancer incidence, with plant-derived compounds - such as polyphenols - often exhibiting antioxidant cancer-preventive properties. Walnuts are an exceptional source of polyphenolic ellagitannins (ETs) that are converted to ellagic acid and various urolithins by gut microbiota in the colon. Urolithin A (UroA) is of particular interest for its potent anti-cancer, anti-inflammatory, and prebiotic activities. However, UroA production in individuals can vary significantly, likely based on differences in gut microbiota. We will substantiate the anti-cancer benefits of a prebiotic/probiotic complex derived from consuming walnuts and determine the basis of human inter-individual variability in UroA formation. Our overall hypothesis is that walnut supplementation improves colonic health and lowers colorectal cancer (CRC) risk through UroA formation. Study Design This is a controlled clinical trial to examine the effects of walnuts on CRC risk factors. Rationale While gut associated microbial metabolism of food-derived ETs is correlated with cardiovascular risk biomarkers, ET metabolism and how it relates to CRC risk has not been evaluated. Urolithins affect numerous cell signaling pathways relevant to cancer. The wide range of urolithin bioactivity provides the rationale for studying their potential cancer preventive properties. As part of an ongoing clinical study of early colonic neoplasia, our laboratory optimized ultra-sensitive analytical pipelines to perform a wide range of 'omics' analyses on human mucosal biopsies. This includes our recent study of the 'adherent' microbiome, raising the possibility that microbiota influence early CRC development, a time when prevention strategies are most efficacious. Our newly published findings demonstrate the feasibility of our analytical pipeline and our ability to associate molecular changes in the host colonic mucosa with the microbiota. Ultimately, these human and preclinical mouse studies may lead to the application of prebiotics and probiotics that enhance formation of protective urolithins for CRC prevention. These studies are of high significance as they will test the ability of the microbiota to generate agents (e.g., UroA) protective of the colonic mucosa. It is possible that high-risk patients can be efficiently converted to a protective state by taking probiotics to realize the full benefits of ET-rich foods. Study Population and Sample Size Men or women between the ages of 45-75 years who are scheduled to undergo a routine screening or surveillance colonoscopy for CRC. A total of 1,200 subjects will be enrolled across two sites (UConn Health and Weill Cornell Medicine). Major Study Interventions Subjects will be asked to consume 2 ounces of walnuts daily for 3 weeks prior to their routine colonoscopy. Food surveys, and blood, urine and stool samples will be collected at 2 time points over the course of study participation. A total of 8-10 colon biopsy specimens will be collected during a subject's colonoscopy procedure for the purposes of this study. Main Outcome Measures/Analyses 1) Association of the presence of colon lesions (AAs or SSA/Ps) with UroA production to assess whether UroA is associated with at-risk patients. 2) Identification and isolation of specific bacteria in the microbiome that either promote or impair urolithin synthesis and metabolism, and determine whether they have probiotic activity. 3) We will test whether the consumption of walnuts can elicit beneficial changes to host microbiota and associated functional metabolites (e.g., bile acids [BAs], SCFAs) in human colon. 4) Fecal (or bacterial) microbiome transplants will test for a causal link between UroA formation and cancer protection.
IRB No. 21-150-2 (Dr. Douglas Oliver, PI): Development of Objective Electrophysiological Tests for Tinnitus Based on Long-Lasting After-Discharges in the Inferior Colliculus
Tinnitus is one of the most common types of disability for military personnel. Tinnitus also affects roughly 10% of the general adult population, nearly 25 million Americans. It is a serious problem for military service members and veterans. In 2015, tinnitus was diagnosed in over 150,000 veterans and was cause for disability benefits in almost 1.5 million veterans. Together, hearing loss and tinnitus represents one of the most common types of disability for military personnel. Compensation for veterans specifically with tinnitus approached $190 million in 2003. The objective of this project is to develop an electrophysiological test for tinnitus based on a newly discovered neural response to sound in the central auditory system, a long-lasting sound-evoked afterdischarge. Tinnitus is the sensation of ringing in the ears in the absence of a corresponding, physical sound. It is a symptom of a pathological response of the auditory system. Unfortunately, the underlying cause of tinnitus is not known, and there is no objective electrophysiological test for tinnitus. The sound-evoked afterdischarge behavior in the auditory system is an activity in the brain that continues after the end of a very long duration sound. In auditory brainstem responses, we have found that the amplitude of the evoked potentials in the brainstem is larger immediately after a long-duration sound than before the sound. This suggests that the brainstem response reflects the time-course of the afterdischarge behavior in single neurons. The main idea being tested in these experiments is that in tinnitus, the afterdischarge behavior becomes continuous, and this would eliminate any difference in the amplitude of the response before and after a long-duration sound. This project will investigate how the afterdischarge activity in the brain is changed with tinnitus. The results from the animal studies will be used to investigate the brain activity potentially related to tinnitus in human subjects with and without tinnitus. The ultimate goal is to develop an objective electrophysiological test for tinnitus that can be used clinically for both military and civilian patients. The methods produced here will benefit research world-wide on tinnitus. The electrophysiological tests developed in this project may be used in both military and civilian clinics to test for tinnitus. Because they only require subjects to listen to sounds at moderate levels while they sit quietly and recording takes place, there is little risk involved. Since the tinnitus diagnosis largely relies on self-reporting by the patient, these tests can screen for tinnitus objectively regardless of the report of the patient. Such tests would verify that patients receiving benefits for tinnitus actually have tinnitus. These tests may show that a normal type of brain activity is modified in tinnitus. If so, it will point to the biological mechanisms that are responsible for tinnitus and speed in its cure. A test developed in this project will allow the condition to be screened objectively as a part of the diagnosis and treatment of hearing and balance disorders.
IRB No. 21-211S-2 (Dr. Matthew Imperioli, PI): Mechanisms for Early Onset Colorectal Cancer
Dr. Daniel W. Rosenberg and his project Co-Investigators are conducting a research study called "Mechanisms of Early Onset Colorectal Cancer" to examine the composition of cells that line the colon wall. Specifically, they will focus on fibroblasts, which are responsible for producing the structural framework (stroma) of connective tissue and coordinating the activities of epithelial, endothelial and immune cells in the tissue. Background & Hypothesis: Fibroblasts can exist in a number of distinct states with dramatically different activities. Resident fibroblasts in healthy tissue are non-dividing cells that help establish tissue architecture and crypt cell dynamics. However, when they are present adjacent to cancerous cells, fibroblasts can become persistently activated as cancer-associated fibroblasts (CAFs), promoting tumor growth and new blood vessel growth, while suppressing immune responses. CAFs can also become senescent and acquire an irreversible senescence-associated secretory phenotype (SASP) that establishes a "permanent" cancer-promoting microenvironment. We propose that the underlying stroma advances rapidly in EOCRC to drive early disease development. Specifically, we speculate that environmental and/or life-style factors cause abnormal fibroblast activation that negatively impacts the normal function of immunoregulatory cells within the stroma, while promoting epithelial cell division. The exploratory experiments proposed here will assess fibroblast proliferation (rapid division of cells), activation and senescence at different stages of cancer development in young patients. Understanding fibroblast dysregulation in individuals at risk of EOCRC could provide important information for understanding the factors responsible for the increasing incidence of EOCRC and ultimately point to therapeutic approaches that reduce this risk. Study Design: This study will screen 100 men or women between the ages of 30-45 years who are scheduled to undergo a routine screening or surveillance colonoscopy. Only patients found to have significant polyps, or healthy control patients, will be included in the final study population. A total target enrollment of 20 subjects (10 subjects found to have significant polyps; 10 healthy (no polyps) sex-matched controls) will fulfill this study's requirements. Main Outcome Measures/Analyses: 1) Study fibroblast populations resected near colonic lesions, 2) Classify fibroblast cell-types from colonic biopsies; Identify activated and senescent fibroblasts, 3) Define the distinguishing set of molecular alterations that characterize EOCRC cases, 4) Determine how a hyper-responsive stromal microenvironment established by activated and/or senescent fibroblasts relates to other stromal events that contribute to the rapid advancement of EOCRC.
IRB No. 21-270-1 (Dr. Cory Edgar, PI): Long-Term Outcomes Following Patellar-femoral Joint Replacement
The purpose of this study is to analyze implant success/failure rates commensurate with outcomes among patients that underwent a Patellar Femoral Joint Replacement procedure (Arthrex iBalance SystemTM). The results of this study may improve our understanding of how patients do after this procedure. This knowledge may benefit future patients who undergo this procedure.
IRB No. 21-174O-2 (Dr. Matthew Costello, PI): Effect of Bladder Interoception on Simulated Driving Performance Under Increasing Cognitive Load
This project will examine how your ability to drive may be affected by the feeling of your bladder, and how this changes in older age. The purpose of this research is to understand how the aging mind and bladder can interact to distract one’s ability to drive a car. In the testing, we will modify and measure your bladder levels while you operate a car simulator. We will also test you in a variety of cognitive and physical tests, and questionnaires that measure thinking ability, physical health, and psychological condition.
IRB No. 21-257-2 (Dr. Matthew Imperioli, PI): The SenDep Study: Linking Molecular Senescence Changes to Depression and Cognitive Impairment in Late Life
Late-life depression (LLD) is a common mental disorder in the elderly, with prevalence rates ranging from 1 to 5%. Recent evidence suggests that LLD is linked to age-related negative health outcomes, such as cerebrovascular disease, increased risk of Alzheimer's disease, vascular dementia, and of premature mortality. The mechanisms of LLD are complex and involve the dysregulation of different biological pathways. Understanding the interplay between the biological changes in aging and depression can provide insight into the mechanisms by which LLD increases the risk of negative health outcomes. This study proposes to evaluate the association of Senescence-Associated Secretory Phenotype (SASP) Index with different clinical phenotypes of aging (i.e., cognitive impairment) and with cellular senescence phenotype (i.e., leukocyte telomere [LT] attrition) in LLD. Finally, we will evaluate the trajectory of changes in SASP, and its relationship with cognitive performance in these individuals. Our hypotheses are that LLD individuals will show a significantly higher SASP index compared to age- and gender-matched never-depressed control subjects. SASP index will be significantly associated with greater cognitive impairment and telomere attrition in LLD subjects. We further hypothesize that an increasing or persistently higher SASP index trajectory will lead to faster cognitive decline among study participants over two years of follow-up. To our knowledge, this will be the first study to examine the association between circulating molecular senescence markers (SASP), a cellular senescence marker (LT attrition), and neurocognitive and clinical characteristics in LLD. Based on the results of this study, we will also be able to identify novel targets for the development of interventions aiming not only the treatment of depression in the elderly but also aiming the prevention of the negative outcomes related to this condition
IRB No. 21-180-1 (Dr. Biree Andemariam, PI): Measurement of Complex Viscoelasticity of Sickle, Normal and Hypoxic Red Blood Cell Mixtures in Sickle Plasma: Implications for Transfusion Therapy
This study is a prospective, clinical/translational research study using blood samples from consenting sickle cell diease (SCD) patients and healthy control volunteers. This study aims to determine the oxygen transport efficiency of red blood cells without oxygen and normal red blood cells (with oxygen) when mixed with blood from patients with sickle cell disease. The primary objective of this study is to test the hypothesis that the complex viscoelasticity of mixtures of SS blood, AA blood and hypoxic red blood cells (HYPX) suspended in SS blood and AA blood will predict oxygen transport efficacy of stored AA blood and hypoxic cell. The seconodary objective is to determine the effects of refrigerated storage duration of AA blood and HYPX on oxygen transport efficiency of the cells. Only SCD patients will be enrolled into this study at UConn Health. Potential subjects who are able to provide informed consent and are at least 18 years of age and have not had a transfusion in the past 90 days will be able to participate. We anticipated enrolling 10 SCD patients. SCD patients will be recruited during routine clinic visits in the New England Sickle Cell Institute (NESCI) and via flyers distributed throughout UConn Health. After consenting to the study, patients will come in for a one time blood draw. One tube will be sent to the JDH for CBC and hemoglobin electrophersis analyses and two tubes will be sent to the Hemanext research lab for research anaysis. The study will continue until full recruitment has been achieved. We estimate this will take approximately one year.
IRB No. 22-144-1 (Dr. Agnes Kim, PI): Echocardiographic Assessment of Pulmonary Artery Pressures
Pulmonary hypertension (PHT) is a complex and challenging hemodynamic condition which is characterized by pathologic increase in mean Pulmonary Arterial Pressure (mPAP) >20 mm of Hg at rest.1 The elevated pulmonary pressures could be due to a variety of underlying causes such as lung disease, left heart disease or disease affecting small pulmonary vessels. The gold standard for a definitive diagnosis of PHT is a right heart catheterization (RHC), done invasively to assess filling pressures.2 Nevertheless, immense improvement in the technology over last few decades has made the noninvasive quantification of pulmonary pressures with increased sensitivity possible by transthoracic echocardiography (TTE).2 Echocardiography, is currently the first imaging modality in patients where PHT is suspected. It not only estimates the systolic pulmonary arterial pressures, but also provides useful information on right ventricle function, left ventricle systolic and diastolic function, as well as valvular disease that might be contributing the elevated pulmonary pressures.3 The goal is to assess the accuracy of mPAP calculated through echocardiographic assessment of PVAT and mPAP obtained through RHC.
IRB No. 22-110-1 (Dr. Isaac Moss, PI): Properties of the Intervertebral Disc Tissue.
Surgical procedures in the realm of orthopaedic medicine often require the removal of the intervertebral disc. While there have been considerable advances in technology, there's a premium on understanding the properties of the intervertebral disc on a cellular and molecular level. Considering spine surgical procedures often result in disc material designated as discard, there's opportunity to bring these samples to the laboratory for exploration as they are otherwise not used or necessary for ongoing patient care.
IRB No. 22-145-2 (Dr. Kai Chen, PI): Effect of Beta-blocker Discontinuation on Functional Capacity and Cardiac Hemodynamics in Patients with Heart Failure with Preserved Ejection Fraction
Heart failure (HF) is a growing public health problem associated with significant mortality and healthcare cost. Heart failure (HF) can be classified into two distinct types based on cardiac muscle contractility measured as ejection fraction - HF with reduced ejection fraction (HFrEF) and HF with preserved ejection fraction (HFpEF). Significant advances in the HF therapy over the past decades have substantially improved the outcome in patients with HFrEF. In contrast, there is no effective therapy available for HFpEF, which remains to be the ";single largest unmet need in cardiovascular medicine";1. Beta-blocker (BB) - The survival benefit of BB in treating HFrEF 3, but not HFpEF, has been well established. Despite of lacking evidence, BB use was shown in 80% of HFpEF patients enrolled in both TOPCAT and PARAGON-HF trials4,5, and in 66% of HFpEF patients in our observational study excluding atrial fibrillation and CAD. This pilot study is to evaluate the effect of beta-blocker withdrawal on functional capacity and cardiac hemodynamics in patients with HFpEF.
IRB No. 22-146O-1 (Dr. Wizdom Powell, PI): Project BrEAtHe (Brothers, Reclaiming, Emotional, Awareness, Tranquility, Healing & Existence): Disrupting Racism-related Stress, Trauma, & Problematic Substance Use
Project BrEAtHe is a research study to create a program focused on mindfulness and stress reduction specifically tailored to young adult Black males (18 to 29 years old) residing in Durham, NC and in Hartford, CT. We plan to use a mobile app on a cell phone to better understand ';real-time'; feedback of experiences of stress due to racism. We are interested in learning about the recruitment and retention of Black males participating in mindfulness based practices. We are also interested in receiving feedback about options to modify and scale a Mindfulness Based Stress Reduction intervention and its preliminary effects on reducing physical and emotional stress reactions and poor coping mechanisms like marijuana and alcohol use linked to everyday racism and discrimination.
IRB No. 18-201COS-1 (Dr. Damion Grasso, PI): Adaptation and Resilience in Childhood Study U01
In the current application we propose applying advances in developmental measurement science, including those developed in our own lab, towards sensitive characterization of interpersonal violence (IV) exposure, biobehavioral indicators of threat detection and reactivity, trauma-related psychopathology, and contextual risk and protective factors in a high-risk sample of preschool age children. Assessment will include (1) the Family Socialization Interview-Modified (FSI-M), a comprehensive interview measuring children's experiences from birth to present, including family stressors, parenting practices and family conflict that was developed in our lab, (2) the Anxiety Dimensional Observation System (ANX-DOS) and (3) the Disruptive Behavior Dimensional Observation System (DB-DOS), two laboratory observation paradigms for characterizing fear/anxiety and anger/affect regulation, respectively, also developed in our lab, (3) a multiple source assessment of trauma exposure and trauma-related symptoms as defined by the DSM-5, (4) attention bias, autonomic (heart rate, skin conductance), and electrophysiological (Event-related potentials) responses to laboratory-based threat stimuli, and (5) observed and reported maternal sensitivity and parent-child interaction. In the current project, families will be recruited from domestic violence shelters and communities surrounding the shelters. Some families will have experienced IV and others will not. Research visits will occur at our child-friendly laboratory on the UConn Kane Street property in West Hartford and will last approximately four hours. Families will be compensated for their time. Should the mother deem it necessary to split the visit due to time contraints, consenting and assessments may be conducted at a different location that the mother deems safe and affords privacy. Specific Aims: Specific Aim 1. To demonstrate that how children respond to negative (threat) stimuli presented in the laboratory is related to their symptoms of fear and distress. Specific Aim 2. To test the hypothesis that how children respond to threat stimuli is the link between their exposure to interpersonal violence and the development of symptoms of fear and distress. Specific Aim 3. To test the hypothesis that mothers' responsiveness to their children will shape children's threat reactivity and the development of symptoms over time.
IRB No. 22-179J-1 (Dr. George Kuchel, PI): A deep longitudinal analysis of next generation influenza vaccines in older adults
This study is a collaboration between The Jackson Laboratory for Genomic Medicine (JAX) in Farmington, CT and UConn Health in Farmington, CT. All recruitment, enrollment, clinical data, and sample collection will occur at the UConn Center on Aging (COA), at UConn Health in Farmington, CT under the direction of Dr. George Kuchel, Professor of Medicine and Director of the UConn COA. Coded samples collected at Visits 1-17 will be securely transported to the Jackson Laboratory for Genomic Medicine (JAX), located on the UConn Health campus, for processing, storage, sequencing, and analysis. Dr. Duygu Ucar will oversee sample management and sample and data analysis per protocol. In this study, a total of sixty (60) healthy adults aged 65 years and older who have had no history of confirmed COVID-19 and have not received influenza vaccination for the approaching influenza season will be enrolled in the study and vaccinated with influenza vaccines approved by the U.S Food and Drug Administration (FDA) and recommended by the Centers for Disease Control and Prevention (CDC) for individuals ≥65 years. All participants receive influenza vaccine during the 2022-23, 2023-24, and 2024-25 influenza seasons. Participants will receive Fluzone® Quadrivalent High-Dose vaccine during the 2022-23 and 2024-25 flu seasons and FLUAD® Quadrivalent during the 2023-24 flu season. Blood samples will be collected from the participants at each of the seventeen study visits over three years. Nasal swab and stool samples will also be collected from participants at 7 time-points across the study period. The study is not designed to assess safety or tolerability of the influenza vaccines administered as part of this proposed study. By performing comprehensive profiling of their blood antibodies and immune cells over time, we will be able to associate specific age-related immune alterations with vaccine responder or non-responder status, thus allowing us to pinpoint biological pathways that can be targeted to enhance vaccine efficacy and that can also help us to progress towards developing a universal influenza vaccine.
IRB No. 22-174-2 (Dr. Zhichao Fan, PI): Investigating Mechanisms and Roles of Integrin Activation of Human Blood Leukocytes in Mitofusin (MFN2) Disease Condition; Charcot-Marie-Tooth Neuropathy (CMT2A)
Using methods of Integrin Activation, our laboratory has demonstrated that β2-integrin-mediated slow-rolling and arrest, but not PSGL-1- mediated cell rolling, are defective in MFN2-deficient neutrophil-like HL60 cells. This adhesion defect is associated with reduced expression of fMLP (N-formylmethionyl-leucyl-phenylalanine) receptor FPR1 (formyl peptide receptor 1) as well as the inhibited β2 integrin activation. MFN2 deficiency also leads to decreased actin polymerization, which is important for β2 integrin activation. Although a rare disease, MFN2 deficiency is responsible for a variety of Charcot-Marie-Tooth (CMAT2A) related neuropathy. Mitochondrial gene mutations are responsible for a great variety of neurologic defects in patients . Mitofusin-2 is ubiquitously expressed in eukaryotic cells, playing a critical role in mitochondrial fusion. MFN2 is essential for β2 integrin activation directly as well as indirectly through FPR1 expression. The synthesis, degradation and homeostasis of synaptic terminal mitochondrial proteins are important to nerve function. Mechanistically, Charcot-Marie-Tooth (CMT) neuropathy and related neuropathies are a heterogenous group of hereditable diseases with length dependent, degeneration of sensory and/or motor nerve fibres. With Next Gen Sequencing applied in the last decade by Inherited Peripheral Neuropathy clinics, up to 90 genes are now associated with CMT neuropathy. CMT2A, is the most common form of ";axonal"; CMT with nerve conduction velocity >38m/s and significant allelic heterogeneity. In this proposed Protocol, by seeking Donation of WBCs from UCH's Neurology patients/referrals with CMT2A, we expect to further knowledge. (*Fan Lab Methodology-See Appendix for Leukocyte Recruitment, Integrin Activation Pathways and Super Resolution/ Flow Imaging Graphics- pg.12-20)
IRB No. 21-143OSC-1 (Dr. Richard Fortinsky, PI): Impact of Perinatal Pandemic-Related Stress on the Early Caregiving Environment, Infant Functioning, DNA Methylation, and Telomere Length
The current study seeks to recruit a diverse cohort of women and their partners who were in the final two trimesters of pregnancy during the COVID-19 pandemic. Phase 1 of the study will involve a large-scale survey (N=2,000) of these individuals to assess perinatal stress exposure occurring in the context of the pandemic. Phase 2 will involve selecting individuals from the Phase 1 survey to establish two subgroups with high (n=200) and low (n=200) perinatal pandemic-related stress exposure to participate in a comprehensive and longitudinal assessment protocol, including interviews, parent-child interactions, an infant stress paradigm, and biological sample collection. Aims are to: (1) use person-centered latent class analysis of perinatal pandemic-related experiences to identify unique profiles that vary on the types and quantity of stress exposure and differentially associate with race/ethnicity, caregiver-reported perceived stress, emotion dysregulation, PTSD, parenting, and infant dysregulation (stress-reactivity and emotional/behavioral problems) in the large Phase 1 survey cohort (N=2,000); (2) Compare infants with high and low perinatal pandemic-related stress and examine caregiver emotion dysregulation, PTSD, and responsive parenting as potential mediators of this relationship in the longitudinal Phase 2 cohort (N=400); and (3) identify differentially methylated regions of DNA and differences in telomere length and changes over time in infants in high v. low perinatal stress groups. Assessment procedures will integrate the experiences and functioning of both the mother and partner when considering implications for offspring. This work will yield mechanistic insight on how pandemic-related stress, caregiver emotion dysregulation, and PTSD influence multiple aspects of the caregiving environment and infant outcomes and is expected to directly inform perinatal public health interventions as the COVID-19 pandemic continues and its sequelae unfold.
IRB No. 22-232-2 (Dr. Juan Salazar, PI): Elucidation of Treponema pallidum-specific antibodies in human syphilitic serum.
Syphilis, a multistage, sexually transmitted infection is caused by the highly invasive and immuno-evasive spirochete Treponema pallidum subsp. pallidum (T. pallidum) (1, 2). Syphilis remains a major global public health threat causing approximately seven million new infections annually (3, 4). Although the efficacy of penicillin therapy for syphilis remains undiminished after more than seven decades of use (1, 5), the explosive resurgence of the disease in the new millennium has fueled a sense of urgency for a vaccine with global efficacy (6, 7) and the World Health Organization has set ambitious targets to reduce the incidence of syphilis by 90% by 2030. T. pallidum is an extracellular pathogen (8, 9), with a low abundance of surface proteins, known as outer membrane proteins (OMPs). OMPs form b-barrels with large extracellular loops (ECLs) that extend from the surface of the organism into the extracellular space. These ECLs are acceptable to antibodies produced during infection with the spirochete. It is generally believed that these antibodies are critical for spirochete clearance and subsequent containment of the pathogen (10, 11). Ex vivo studies have demonstrated that antibodies in human syphilitic serum promote uptake and degradation of T. pallidum by professional phagocytes, such as macrophages (12, 13). The exact target(s) of the antibodies present in human syphilitic serum that lead to uptake of the spirochete has yet to be determined. Strategies for vaccine design often are predicated on the ';learning from nature'; paradigm that immunization should mimic the protective response evoked by the infecting pathogen (14). Extrapolating to syphilis, a successful vaccine should elicit antibodies against targets on the T. pallidum surface, with opsonic activity serving as an ex vivo correlate of protective immunity (10, 11). Having knowledge about the antigenic response to T. pallidum OMPs, more specifically ECLs, of a given serum sample or ECL-specific monoclonal antibodies in the ex vivo human macrophage system may give rise to novel vaccine candidate against an organism that has been plaguing mankind for centuries Hypotheses or Research Question, Aims and Objectives: Hypothesis/Question: To address the above information gaps, this study seeks to illuminate the key antibodies present in human syphilitic serum that lead to the clearance of spirochetal infection. Aims / objectives: Confirm samples of syphilitic serum evaluated have opsonic potential to pathogenic spirochetes. Use an ex vivo human macrophage system to investigate how human syphilitic serum and/or T. pallidum-specific monoclonal antibodies influence innate immune responses. Study how the antibody-opsonized spirochetes shape innate responses imminent adaptive responses in syphilis.
IRB No. 22-255-2 (Dr. Zhichao Fan, PI): Mechanisms and Roles of Integrin Activation of Cystic Fibrosis Leukocytes
The immune system is the body';s defense against infectious organisms and other invaders. Integrins are key mediators in immunity for the recruitment of white cells which play critical roles in inflammatory diseases. Insights about Integrin function hold out the prospect of improved disease prevention and drug discovery. Integrin molecules stick to body surfaces or cells. They are vital to the successful functioning of the inflammatory response at the source of an insult. In response to inflammation or infection, white cells stick to nearby blood vessels and then crawl along the surface until they can squeeze out of the blood vessel into tissues where they must act. Studying and super imaging these mechanisms and the roles of integrin during this activation will bring new insights about leukocyte recruitment and leukocyte immune functions as well as invite discovery of novel treatments for infectious and inflammatory diseases. This project is investigating how integrins may also affect blood vessels as commonly seen in human heart disease.
IRB No. 21-037S-2 (Dr. Matthew Imperioli, PI): Enhancing the Capacity of School Nurses to Reduce Excessive Anxiety in Children: An Efficacy Trial of the CALM Intervention
Project Summary/Abstract Title: Enhancing the Capacity of School Nurses to Reduce Excessive Anxiety in Children: An Initial Efficacy Trial of the CALM Intervention Topic and Project Type: Education Research Grant, CFDA Number: 84.305A, Social and Behavioral Context for Academic Learning, Project Type: Initial Efficacy Purpose of the project: Excessive anxiety among elementary students is highly prevalent and associated with impairment in academic, social, and behavioral functioning. The primary aim of this project is to evaluate the initial efficacy of a brief nurse-delivered intervention (CALM: Child Anxiety Learning Modules), relative to a credible comparison (CALM-R, relaxation skills only) for reducing anxiety symptoms and improving educational outcomes at post intervention and at a one year follow-up. In addition, we will assess the cost effectiveness of CALM versus CALM-R, and examine potential predictors, moderators, and mediators of CALM';s impact on child outcomes based on the proposed theory of change. Setting: Elementary schools in Connecticut and Maryland from urban, suburban, and rural areas. Sample: 30 elementary school nurses will be randomized and trained in one of the two interventions; 218 children ages of 5 to 12, with elevated symptoms of anxiety from participating schools will be recruited. Nurses and children of all races/ethnicities are eligible. Intervention: CALM is a fully developed intervention that was pilot tested with the support of an IES-funded Goal 2 grant. CALM consists of five modules based on empirically supported cognitive behavioral strategies. Data from our IES-funded pilot RCT demonstrated the feasibility of the nurse training and intervention in an authentic school setting, adequate nurse fidelity, and promising positive changes on key student outcomes and across multiple informants. Control condition: CALM-R is an active, credible comparison condition. It consists of five modules (to control for time with nurse) and is based on relaxation skills only, to mimic what some nurses already use with students. Research design and methods: A clustered randomized controlled design will be used to compare the impact of CALM to CALM-R on student anxiety symptoms and academic, social, and behavioral functioning. Key measures and outcomes: Key outcome measures will assess reductions in anxiety symptoms (e.g., using the Clinical Global Impressions Severity and Improvement Scales measured by independent evaluators) and improvements in academic functioning (e.g., using the Academic Competence Evaluation Scale measured by teachers blind to intervention condition). Additional outcomes (e.g., grades, school attendance) and mediators (e.g., behavioral avoidance, somatic symptoms, maladaptive cognitions) are assessed using multiple informants and methods. Data analytic strategy: The impact of the intervention on anxiety symptoms and educational outcomes will be assessed using multilevel mixed effect models and three time points: pre, post and follow-up. Our hierarchical model will have two levels, with children';s scores on the first level and being clustered within nurse on the second level. We will include both child-level and nurse-level covariates. Cost Effectiveness Analyses: A secondary aim of this project is to examine the cost effectiveness of CALM versus CALM-R. Data will be collected from multiple sources to analyze the incremental cost-effectiveness ratio, intervention and implementation costs, and willingness to pay from school administrators.
IRB No. 21-167JSO-1 (Dr. Daniel Rosenberg, PI): Microbiota, Metabolites and Colon Neoplasia
Dr. Daniel W. Rosenberg and his project Co-Investigators are conducting a research study called "Microbiota, Metabolites, and Colon Neoplasia" to examine whether eating walnuts can have a beneficial effect on the gut bacteria population, inflammatory markers in the blood, and the tissue that lines the inside of the colon. This is a 29-day dietary intervention study where participants will be asked to consume 2 ounces of walnuts daily for 21 days, and at the end of the study period they will come in for a routine colonoscopy. After being informed about the study and potential risks, participants giving written informed consent will first start a 7-day wash-out period where they will be asked to avoid foods high in ellagitannins (ET) for the duration of the study. In addition, participants will be asked to complete food and activity questionnaires, a walnut consumption log, and two sets of 3-day dietary records during their participation in the study. Participants will also be asked to provide three urine samples, two blood samples, and two stool samples at multiple time points, and 8-10 colon tissue specimens (biopsies) will be collected during their colonoscopy procedure for the purposes of this study.
IRB No. 22-287-2 (Dr. Kevin Manning, PI): Apathy: An Early Manifestation of Frailty and Disability in Older Adults with Depression?
The overall objective of this research is to understand whether a subtype of depression in older adults - apathy - heralds the onset of disability. This pilot project will test the hypotheses that there will be differences in functional performance and blood-based biomarkers between older depressed adults with and without apathy.
IRB No. 22-330S-1 (Dr. Angela Bermudez Millan, PI): Implicit Affectivity and Transition to a Plant-based Diet
This pre- and post-test study design aims to identify the impact of dietary change on mood. We will follow for three-months a sample of 30 adults that transition to a plant-based diet. The main outcome is the Implicit Positive and Negative Affect Test. Participants will complete this assessment at baseline and at 3-months. We may be able to associate dietary intake changes with changes in affect. This could help describe the underlying mechanisms that lead to depression. In doing so this study may serve to emphasize the importance of diet in managing depression risk. Specific Aim 1: To examine the change in plant and animal-based intake after transition to a plant-based diet. Specific Aim 2: To examine the change in implicit affectivity in adults after transition to a plant-based diet. Specific Aim 3: To examine the association between plant-based intake and implicit affectivity.