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Clinical Trials: All
IRB No. 02-200-1 (Dr. Bruce Liang, PI): Molecular Correlates of Atrial Fibrillation
Study description not available
IRB No. 02-288-2 (Dr. Anna Dongari-Bagtzoglou, 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. 07-252-2: 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: 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. 09-010-1 (Dr. Rajesh Lalla, PI): Oral Mucositis Research Registry/Repository
Oral Mucositis refers to mouth sores that occur in cancer patients due to the chemotherapy or radiation therapy that they receive. The Oral Mucositis Research studies related to oral mucositis or cancer and to identify potentially eligible subjects for future research. The Oral Mucositis Research Repository will hold in an identifiable format, any remaining tissue or blood samples or derivatives thereof for use in oral mucositis or cancer studies, at the conclusion of the study for which they were collected.
IRB No. 11-027-2 (Dr. Susan Tannenbaum, PI): UCHC Cancer Center Research Screening
Study description not available
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. 13-119-2 (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. 14-107-6 (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. 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. 01-127H-2 (Dr. Kazuya Machida, PI): Signalosome-oriented Phosphotyrosine Profiling of B-cell Malignancies
Study description not available
IRB No. 17-045-2: 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. 17-155-3 (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. 13-087-3.2 (Dr. Susan Tannenbaum, PI): Factors Influencing Fatigue in Breast Cancer Patients Undergoing Breast Irradiation
Study description not available
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. 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. 19-214-1 (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: 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. 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. 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. 17-180H-6.2 (Dr. Erin Mead-Morse, 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. 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. 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. 20-123-1 (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. 20-230-2 (Dr. Kourosh Parham, 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: 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. 21-046-2 (Dr. Kevin Manning, PI): Cognitive Remediation of Cognitive Control in Late-Life Depression
This research is being completed because depressed older adults commonly experience difficulties with concentration and processing speed, also called executive dysfunction, as well as negative affect/emotions (e.g., low mood, irritability, worry). Older adults with depression and executive dysfunction and/or negative affect/emotions regularly fail to get better with conventional antidepressant medications. Therefore, the purpose of this study is to use an established non-invasive treatment (computerized brain-training) that may improve cognitive and depression related outcomes in older adults. There are two aims of the current study. We are interested in whether a computerized braintraining treatment will improve thinking and depression in older depressed adults. We are also interested in whether participating in the treatment will result in changes to brain activity measured with magnetic resonance imaging (MRI).
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. 21-149J-1 (Dr. George Kuchel, 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. 21-257-2 (Dr. Breno Diniz, 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. 22-146O-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. 22-114OS-1 (Dr. Golda Ginsburg, PI): Transitioning Emotionally and Academically to Middle School Successfully: Development of a Brief Intervention to Reduce Student Anxiety (TEAMSS)
Project Summary/Abstract Title: Transitioning Emotionally and Academically to Middle School Successfully: Development of a Brief Intervention to Reduce Student Anxiety (TEAMSS) Topic: Social, Emotional and Behavioral Competence Project Type: Special Education Research Grant, CFDA Number: 84.324A,Social and Behavioral Outcomes to Support Learning, Development and Innovation Purpose: The transition from elementary to middle school is difficult for most students and specialized transition supports are critical for students receiving, or at risk of needing special education services. Excessive anxiety, part of the definition of "emotion disturbance" under IDEA, is the most common form of psychopathology and severely impairs academic functioning. Currently, no intervention exists to support this high risk group during their transition to middle school. The purpose of this application is to develop and assess the feasibility of a brief multi-component intervention, delivered by school clinicians, to reduce anxiety symptoms and improve academic and social functioning. The project proposes an iterative development process (i.e., expert review, two open trials, and pilot RCT) to achieve these goals. Project Activities: TEAMSS is an intervention for students in regular and/or special education classrooms with excessive anxiety as their primary concern. The development of TEAMSS will occur in three stages. In Stage 1, we will establish a development workgroup who will assist us in refining the intervention and study methods. In Stage 2, two sequential open trials of the revised protocol will be implemented at 3 middle schools with about 15-20 students with excessive anxiety. In Stage 3, a pilot RCT will occur at 4-6 middle schools and about 42 students will be enrolled. The RCT will occur in three phases: Phase 1, students will be assessed for eligibility (Baseline 1) at the end of elementary school and randomized to receive TEAMSS or enhanced usual care (EUC). In Phase 2, those in TEAMSS will begin group sessions within two weeks of starting middle school. At the end of the intervention (i.e., 10 weeks later), students randomized to both conditions will complete a post evaluation (i.e., December) and a follow-up evaluation in May (i.e., 5 months after their post evaluation). Products Expected: After engaging in an iterative process of designing, testing, and refining the intervention, it is expected that a fully formed intervention (manual, handouts, training materials), aimed at helping students with anxiety transition to middle school, will be available. Data from the RCT will inform schools and the field whether implementing a brief intervention to support the transition to middle school for students with anxiety is feasible and has an impact both on anxiety and academic outcomes. Dissemination of the intervention and study findings will occur at the local and national level. With respect to local dissemination, we will present to our participating school/districts, at statewide conferences and to the Board of Education. At the national level, research staff will publish findings in peer-reviewed journals and at present at local and national conferences (e.g., National Association of School Psychologists). Setting: Connecticut elementary schools from a mix of urban and suburban districts. Sample: A total of 90 fifth grade students with elevated anxiety symptoms or disorders will participate in this study. Within the participating CT districts there are 51 elementary schools and 20,000 students. The student body within CT is diverse in terms of gender, socioeconomic status, and racial/ethnic background (12.3% African American, 22.1% Hispanic/Latino, 57.3% Caucasian, 4.8% Asian, 2.5% two or more races; 32.9% receive free/reduced priced meals). Intervention to be developed: TEAMSS will be an innovative program based on empirically supported cognitive behavioral strategies for anxiety reduction. The initial version of TEAMSS includes a six session student group, two parent group sessions, and teacher consultation meetings. The content of TEAMSS includes anxiety psychoeducation, behavioral exposure, cognitive restructuring, relaxation strategies and social and organizational skills for students, as well as strategies for parents and teachers to reduce anxiety-promoting behaviors. Control: To ensure adequate recruitment and retention, the control condition during the pilot RCT will be EUC, which will include written materials for families (e.g., resources on student anxiety, tip sheets on successful transitions to middle school) and formal visits with the middle school clinician in the spring of last year of elementary school. Primary research method: This project will be implemented in three stages. In Stage 1a "TEAMSS Development Workgroup" (TDW), comprised of national experts and school personnel, will provide input on the intervention and study protocol. Stage 2 involves two sequential open trials at 3 middle schools with about 15-20 students with excessive anxiety. In Stage 3a pilot RCT comparing TEAMSS and EUC with 4-6 school-based clinicians, at 4-6 middle schools and about 42 students will be conducted. Key outcomes measures: Using a multi-method multi-informant approach, key outcomes will assess feasibility and acceptability (e.g., clinician knowledge and fidelity of TEAMSS, satisfaction, recruitment/retention) and student outcomes (e.g., social-emotional, behavioral, and educational outcomes). Exploratory outcomes will assess mediators outlined in the proposed theory of change and data on costs will be collected. Data analytic strategy: Feasibility and acceptability analyses will be descriptive (e.g., recruitment, adherence, satisfaction). In the RCT, impact of TEAMSS vs EUC on key outcomes will use mixed effect models. Covariates may be included in the analysis to correct for imbalance if it is deemed necessary. Cost Analysis: Measures will assess TEAMSS costs (i.e., to schools, districts) as well as savings resulting from impacts on academics, special education and specialty mental health service utilization. We will obtain data on TEAMSS training and implementation costs at one of the participating schools, and use these data to estimate the overall costs of implementing and delivering TEAMSS.
IRB No. 21-143OSC-1 (Dr. Damion Grasso, 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. 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. 22-327-1 (Dr. Biree Andemariam, PI): Bone Loss, Physical Function and Frailty in Older Women with Sickle Cell Trait
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 in older women. 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. 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 investigate whether women with SCT have reduced decreased muscle function, decreased muscle mass, and increased frailty compared to women without SCT. Frailty is a common clinical syndrome in older adults that carries an increased risk for poor health outcomes, including falls, incident disability, hospitalization, and death. This study will try to fill a knowledge gap in the scientific literature. It may potentially reveal a previously unrecognized risk factor for disability and address potential health disparity in African descent women.
IRB No. 22-314-2 (Dr. Flavio Uribe, PI): A Randomized Clinical Trial Comparing the Effect of Force Magnitude on the Rate of Canine Retraction and Gingival Crevicular Fluid Proteome Profile
lay Summary:. This research is being done to examine the effect of force level in orthodontic treatment plans here at UConn Health/SODM. Force level is the amount of force the orthodontic devices are putting on your teeth for movement. To better understand the effects of force levels, information is collected. Researchers will also collect the fluid that naturally releases from your gums, dental molds obtained with an intraoral digital scanner, picture (x-ray) of specific teeth to evaluate the eye tooth region on the upper jaw on both sides, during orthodontic treatment. Participants are having teeth removed and braces fit to their teeth for orthodontic treatment. The only difference bewtween standard of care and this study is that when the remaining teeth are pushed together to fill the space left by removing some teeth the braces will put about two and one half times as much pressure on half of their teeth as is usually used. This pressure will be applied with the braces remaining on for up to 17 weeks. Treatment will be starting from pulling back your eye teeth for 16-17 weeks to close the space of the pulled out upper premolars. The premolars are the teeth behind to the eye teeth. The space provided by the pulled out premolars will be closed by the pressure behind the back of the eye teeth in the upper jaw. Study visits will be scheduled on dates of routine orthodontic appointments with the addition of 20- 45 minutes to each orthodontic appointment depending upon the sample collection procedures. Only one appointment will be scheduled 1-2 weeks after the first appointment, and the other four appointments will be four weeks apart. The right and left sides will be randomly selected for high or low pulling forces. A high force is considered when an orthodontic force of more than 200 grams is being used to move an eye tooth back. Low pulling forces, or conventional force level is approximately 150 grams to move an eye tooth back. The researchers will decide this after you (your child) decide to join. You (your child) choose from a bunch of closed envelopes assigning one side for the light pulling force and the opposite side for the heavy force. The fluid that naturally releases from your gums and dental molds obtained with an intraoral digital scanner, and periapical radiographs of upper jaw eye teeth (x-rays) are obtained. The information to be collected by the researchers may lead to better and/or quicker treatment results for others in the future. All those who participate in this study will receive standard care in the UConn Health/School of Dental Medicine Orthodontic clinic, which they may benefit from Because of the research activities, there is a slight risk to you (your child) from participating in this research study- (slightly more than braces treatment). Giving the collection of the fluid that naturally releases from your gums or recording of the dental molds obtained with an intraoral digital scanner are slightly uncomfortable for some; you (your child) can take as much time as needed to complete these tasks on research visits. Research procedures will be conducted on the same day and place as your regular care for orthodontic treatment. We will also be taking two periapical radiographs of the eye teeth (two time-points) of the upper jaw region at T0 (The first visit of the study) and T5 (after 16-17 weeks) to better understand the changes in the root length following the course of treatment. This amount of extra x-ray exposure is minimal. Hypotheses, Aims, and Objectives: Hypothesis: Null Hypothesis Primary Outcome: Rate of canine retraction. We hypothesize that there is no significant difference in the rate of canine movement between the light force and the heavy force levels. Secondary Outcome: external apical root resorption (EARR), movement of the anchorage teeth (maxillary first molar), type of canine movement (rotation, extrusion, and tipping), and biomarkers evaluated through GCF. We hypothesize that there is no difference in magnitude of anchorage loss, root length of canines, the type of canine movement, and the expression of biomarkers between light and heavy force levels. Alternative Hypothesis There is a significant difference in the primary outcome (rate of canine retraction) and the supportive outcomes (cytokines and the amount of particular protein/polypeptides/antibody extracted from GCF). Aims/objectives: To compare the effect of light force and heavy force on the rate of orthodontic tooth movement (retraction of maxillary canines). To evaluate the effect of force magnitude on the root length of maxillary canines. To compare the effect of light force versus heavy force on the rate of anchorage teeth movement. To describe the type of canine displacement (degree of tipping, rotation, and extrusion) during space closure with light versus heavy force. To compare the expression of biomarkers with heavy force versus light force.
IRB No. 23-089-2 (Dr. Cutter Lindbergh, PI): Computerized Cognitive Remediation of Long COVID Symptoms in Older Adults
Evidence is mounting that a significant minority of patients who develop coronavirus disease 2019 (COVID-19), especially older adults, show lingering neuropsychiatric symptoms including cognitive impairment, brain fog, and depression. These neuropsychiatric symptoms -- which are commonly referred to under the umbrella term "Long COVID" -- are debilitating and may last for months or even years after viral infection. There is a severe lack of evidence-based treatments. The purpose of the present study is to help address this public health crisis by determining whether computerized "brain-training" treatment has potential for improving thinking, mood, and other aspects of day-to-day functioning in older adults with Long COVID. There are two main aims of the present study. The first aim is to simply determine the "feasibility" of using brain-training treatment in older adults with Long COVID. This includes examining whether Long COVID patients are willing to engage in the treatment and whether they find the treatment acceptable and credible. The second aim is to gather preliminary data on whether the brain-training treatment appears to improve memory, thinking, mood, and other aspects of daily functioning in older adults with Long COVID.
IRB No. 23-079-1 (Dr. Scott Mallozzi, PI): Advanced Techniques in Intraoperative Monitoring for the Lateral Lumbar Interbody Fusion Procedure: A Utility Study
This study is designed to evaluate the clinical utility of a known intraoperative neuromonitoring modality (SSEP) using a nontraditional stimulation site (saphenous nerve versus more traditional posterior tibial nerve) to try to better identify nerve health changes to the lumbar plexus, which is at risk during the LLIF procedure. To quantify the clinical utility of saphenous nerve SSEP monitoring in predicting and/or mitigating new postoperative neural deficits following LLIF surgery.
IRB No. 23-134-2 (Dr. Julie Robison, PI): UConn Pepper Center (OAIC) Recruitment Volunteer Registry
Objective/Goals: The Research Volunteer Registry (RVR) is a mailing list that is used to invite and share opportunities to participate in future research studies and to community educational events the UConn Pepper Center will host.
IRB No. 19-214S-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. 23-193J-1 (Dr. Eric Wang, PI): Healthy Control Blood Collection to Investigate Mechanisms of Leukemogenesis and Therapy Resistance
Specific Aim To collect fresh healthy human blood for use in developing and optimizing co-culture assays with human malignant cell lines upon genetic and pharmacologic perturbation of gene candidates identified for therapy resistance. In addition, we will use healthy donor specimens to perform high-throughput genomic analyses compared to our human leukemia cell lines and use the leftover specimens as healthy controls for future research projects. Design and Outcomes This is a prospective, single-site study that will collect human blood specimens (50ml) from healthy adult participants Sample Size, Population, Interventions and Duration In this study, up to 20 healthy men and women participants, ages 18 and older will be enrolled at the UConn Health Clinical Research Center in Farmington, CT. Study participation will involve consent followed by a single visit lasting 30 minutes for blood and data collection.
IRB No. 23-179-1 (Dr. Andrea Shields, PI): Xenobiotic transfer of Tranexamic acid (TXA) using an ex vivo placental perfusion model: a pilot study
To our knowledge, there are no studies that have researched if tranexamic acid (TXA) has an effect on the placenta, or if there is considerable transfer of the drug from maternal to fetal circulation. We propose studying the transfer of the drug on a single placental lobule of 7 placentas. We hypothesize that given the large molecular composition of tranexamic acid there will be minimal transfer of the drug in the ex-vivo placental perfusion model, thus providing safety data on the administration of tranexamic acid for therapeutic indications especially during pregnancy. The specific aims are: 1) To set up and troubleshoot the placental perfusion model using 3-5 placental lobules 2) To measure and compare the levels of therapeutic tranexamic acid in the maternal versus fetal perfusate collected from an ex-vivo placental perfusion model.
IRB No. 23-169H-1 (Dr. Benjamin Ristau, PI): Prostate cancer detection during transperineal prostate biopsy using cognitive versus software-based MRI-fusion
This study will examine differences in clinically significant cancer detection during transperineal prostate biopsy based on whether samples were obtained using a cognitive or software-based fusion technique. This will be a retrospective analysis of a multi-institutional cohort.
IRB No. 23-190SSF-2 (Dr. Andrea Shields, PI): Meals 4 Moms: Development and Feasibility of a Multilevel Community-based Lifestyle Intervention for Gestational Diabetes
Gestational Diabetes Mellitus (GDM) affects 2-10% of pregnancies in the US and 50% of GDM patients will progress to develop Type II Diabetes Mellitusin their lifetime. GDM can also cause pregnancy complications including antepartum hospitalization, cesarean delivery and longer length of stay during antepartum or delivery admissions. Improving pregnancy outcomes involves patients understanding and adopting to an ADA specific diet, daily glucose monitoring and physical activity and compliance with prenatal visits. Providing education during pregnancy is the optimal window of opportunity for the prevention of diabetes. In Phase 1 of the study, the team of investigators will develop a novel, personalized lifestyle intervention (Meals 4 Moms Bundle) for pregnant patients diagnosed with GDM to supplement the usual care and education that is provided to such patients. The bundle will include additional GDM education, nutrition and exericse guidance, GDM meal kit delivery and support. Prior to implementation of the bundle, focus groups (with current GDM patients) to solicit feedback on the bundle materials will be conducted. Phase 2 of the study will involve a pilot feasibility randomized clinical trial which includes UConn Health patients diagnosed with GDM. Patients will be randomly assigned to receive usual obstetrics care for patients who are diagnosed with GDM or usual care plus the Meals 4 Mom Bundle. The clinical trial will assess the feasibility and acceptability outcomes of recruitment rate, retention, adherence to diet and exercise recommendations and acceptability with the program.
IRB No. 24-023J-2 (Dr. Paul Robson, PI): An open resource of human induced pluripotent stem cells lines from diverse population groups
Specific Aims 1. Establish well characterized male and female human induced pluripotent stem cell lines (iPSCs) lines from genetically diverse healthy individuals. 2. Establish clonal sublines from a subset of karyotypically normal iPSC lines and assess their capacity for differentiation and suitability for genome editing. 3. Expand and archive a selected subset of normal, pluripotent iPSC clonal sublines and perform whole genome sequencing (WGS). 4. Release selected iPSC sublines and their genome sequences for distribution to the research community on a cost-recovery basis. Design and Outcomes Participants will provide blood samples (10-15ml) at a single visit for development of iPSC lines with consent for future research use and distribution of iPSC lines to the research community and sharing of genomic data in publicly accessible databases. Sample Size, Population, Interventions and Duration: Up to 103 self-reported healthy adult participants (both male and female) will be enrolled in the study for a single visit lasting 30 minutes. While somewhat restricted based on enrollment we will aim to recruit individuals with the following self-reported ancestry: African/African American (n=30), Latin American/Hispanic (n=20), East/Southeast Asian (n=8), South Asian (n=14), European/White (n=8), Middle Eastern (n=10), and Other (n=13) populations.
IRB No. 23-111SO-2 (Dr. Golda Ginsburg, PI): Managing Anxiety in Pediatric Primary Care (MAPP): A Pilot Trial of the Anxiety Action Plan (AxAP)
Anxiety disorders in youth are: 1) the most prevalent psychiatric disorders, 2) associated with severe disability, and 3) considered gateway disorders--as they predict a broad range of adult psychiatric and functional problems [1-6]. Despite the high prevalence and impairment, less than half of anxious youth receive mental health services, and access to evidenced-based interventions lags far behind that of less common psychiatric illnesses [7, 8]. For instance, in a primary care setting, only 31% of anxious youth, compared to almost 80% of youth with attention deficit hyperactivity disorder, received mental health treatment in the past year [8]. To address this ";mental health service gap,"; researchers [9-11] along with the Surgeon General [12] have recommended: 1) offering evidence-based mental health services in community settings frequented by children (i.e., to have co-located or integrated mental health services in primary care), 2) enhancing the capacity of existing community providers who interact with youth (e.g., primary care providers; PCPs), and 3) improving identification and early evidenced-based interventions in community settings to reduce the need for specialty mental health treatment. This proposal responds to these recommendations, as well as those by the American Academy of Pediatrics [13] to close the mental health service gap by enhancing the capacity of PCPs to deliver a brief mental health intervention in pediatric primary care. Primary care settings are ideal for addressing pediatric anxiety specifically because: 1) prevalence rates of excessive anxiety are high in primary care (approximately 10-20%) [6], 2) over 90% of anxious youth report physical complaints (e.g., stomach aches) and are ";frequent flyers"; in primary care settings [14, 15], 3) children with, compared to without, medical conditions treated by PCPs are more likely to have elevated anxiety [16], and 4) PCPs are often the first and only health professional children visit [17]. This three year R34 application also responds to NIH';s priorities in PAR-MH-21-131: Pilot Effectiveness Trials for Treatment, Preventive and Services Interventions (R34) aimed at testing interventions with previous efficacy in community settings using novel service delivery methods. Specifically, we propose to refine and assess the feasibility of the Anxiety Action Plan (AxAP), a brief intervention to reduce pediatric anxiety, delivered by PCPs (defined here as nurses, nurse practitioners, physician assistants, and/or pediatricians) in community pediatric primary care clinics. This proposal builds on the PI';s initial feasibility work with PCPs (see Preliminary Studies) [18] conducted as part of the NIMH-funded Center for Mental Health in Pediatric Primary Care. The AxAP, modeled after the Asthma Action Plan familiar to PCPs, is based on the core therapeutic element of CBT for anxiety (i.e., behavioral exposure) [19], was designed to fit within the short primary care visit (20-30 minutes), is brief (1-4 sessions), harnesses technology by using virtual training, assessment, and an option for virtual visits, and can be billed for as an office visit. Uniquely, and in stark contrast to co-location or integrated treatment models, the goal of the AxAP is to enhance the capacity of PCPs to identify and intervene with anxious youth. Importantly, enhancing the capacity of PCPs, rather than adding co-located mental health specialists, increases the reach of the intervention and the number of interventionists available and trained to identify and reduce anxiety, particularly in communities where access to specialty mental health specialists is limited. The proposal also incorporates several additional innovative features including: 1) the development and pilot testing of cost-benefit measures of the AxAP and 2) pilot testing of AxAP target mediators at the child, parent, and PCP levels. Primary Aims To refine and assess the feasibility of the AxAP and study methods (e.g., PCP training, adherence measures, control condition materials) during an open trial and with feedback from a development advisory team comprised of experts in the field. To conduct a pilot randomized controlled trial of AxAP, relative to Enhanced Usual Care, for reducing anxiety severity and impairment at post-intervention (2 months after randomization) and at a 4 month follow-up (6 months after randomization) with 6-12 PCPs and 60 anxious youth (ages 6-17). Secondary/Exploratory Aims To pilot measures for investigating theory-based intervention targets of AxAP including changes in: 1) PCP knowledge and skills in anxiety reduction strategies; 2) reductions in child behavioral avoidance and 3) reductions in parental accommodation of child anxiety. To refine and pilot measures to be used in a cost-benefit analysis of AxAP in a future large scale effectiveness trail (R01).
IRB No. 24-127J-1 (Dr. George Kuchel, PI): Hematopoietic epigenetic memory as a driver of inflammaging
This is a prospective, single-visit study. The UConn Center on Aging will recruit 80 healthy community-dwelling young (20-35 years old, n=40: 20 men, 20 women) and older adults (>65 years old, n=40: 20 men, 20 women). Blood samples (50 mL, single draw) will be collected from these participants and participants will be clinically assessed using Frailty Index, frailty phenotype and blood-borne measures of biological aging. This research is being done to determine how aging affects the rare blood stem cells that give rise to the circulating immune cells.. Scientists may conduct genomic testing of cells in blood in this research. This means that they will be looking at which genes are turned on and which are turned off in immune cells. This study may help contribute to new strategies to rejuvenate the immune system and responses.
IRB No. 24-066-2 (Dr. Iman Al-Naggar, PI): Mito-LUTS: A Pilot Study of the Effect of MitoQ on Lower Urinary Tract Symptoms in Older Women with Metabolic Syndrome
Objectives: The goal of this pilot study is to serve as proof-of-concept that using MitoQ, a supplement with gerotherapeutics properties, to target shared biological pathways between aging, metabolic syndrome and lower urinary tract symptoms (LUTS) represents a much-needed novel direction in alleviating lower urinary tract symptoms. It will also help identify and validate biomarkers described in the literature for LUTS diagnosis and severity and generate data required to design and power future clinical trials. Aims: Aim 1: Elucidate the effect of MitoQ on lower urinary tract symptoms (LUTS) in older women with MetS. We will carry out a double-blinded, placebo controlled randomized pilot and exploratory study to test the effect of MitoQ on LUTS in older women with MetS. Older women (50-75 years) with both LUTS (no UTI, with urgency possibly accompanied by other symptoms such as frequency, urgency or urge incontinence for at least 3 months), and MetS (International Diabetes Federation (IDF) definition) will be randomized 2:1 into a treatment (40mg/day MitoQ, for 16 weeks) and placebo arm (Total number of participants will be 50). Assessments of LUTS using well-validated questionnaires and 3-day voiding diaries will be done at baseline, during, and at the end of the drug administration period. Main outcome will be change in LUTS questionnaire scores from baseline for each individual and between Placebo and MitoQ groups. We hypothesize that treatment with MitoQ will improve LUTS questionnaire scores in females with MetS, whereas the placebo group scores will remain unchanged or worsen Aim 2: Measure the effect of MitoQ on biomarkers and their biomarkers and their correlation with LUTS severity. There are currently no clinically useful biomarkers that are specific for LUTS, and novel biomarkers that can reliably distinguish LUTS are urgently needed. A good biomarker would also help with choice of therapy, predict response, change with an intervention and reflect changes in symptom severity. Aim 2a: Does treatment with MitoQ in females with MetS-related LUTS alter blood and urinary biomarkers of biological hallmarks of aging and LUTS? We will measure biomarkers of inflammation and oxidative stress in blood and urine at baseline and 16 weeks after treatment initiation in our participants. We will also measure urinary proteins and metabolites shown to correlate with overactive bladder syndrome (OAB) and others reported to be urotoxic or uroprotective. Values will be compared to baseline for each subject and means will be compared between groups. We hypothesize that MitoQ will reduce biomarkers of inflammation, oxidative stress, and OAB, while also decreasing urotoxic metabolites and increasing uroprotective metabolites. Aim 2b: Do changes in biomarkers correlate with types of LUTS and their severity? In order to be clinically useful, a biomarker should correlate well with LUTS type and severity. Biomarker levels will be correlated to LUTS questionnaire scores and voiding diary parameters. Because LUTS can have multifactorial etiology, no single biomarker has been useful. We aim to identify a panel of biomarkers for diagnosis, prognosis, tailoring, and tracking interventions. We hypothesize that changes in biomarkers will reflect changes in LUTS and correlate with LUTS severity. Study Design: This will be a randomized, placebo-controlled, double-blinded pilot and exploratory study. Participants in the MitoQ intervention group will receive MitoQ capsules (40 mg/day), whereas placebo control group will receive capsules containing all inactive ingredients prepared by the same manufacturer without the MitoQ, for 16 weeks.
IRB No. 24-094-1 (Dr. Omar Ibrahim, PI): Before-After Operational Data Collection Study Protocol - UConn
The diagnosis managment of lung nodules can be difficult. Current guidelines recommend that pulmonary nodules are managed based upon their probability of malignancy. Despite established guidelines, prior studies estimate that 60-70% of patients with ILNs are not followed up in a timely fashion in accordance with guidelines. To address the management and diagnostic challenges, Optellum has developed Virtual Nodule Clinic (VNC). VNC is an FDA-cleared, web-based, end-to-end software solution early lung cancer diagnosis. University of Connecticut Health (UConn) will be using VNC for routine clinical management of pulmonary nodule patients. As such, UConn offers an ideal environment in which to evaluate the real-world clinical utility of VNC. As part of this partnership, UConn will work with Optellum to evaluate whether use of VNC leads to an improvement in the number of pulmonary nodule patients being followed up and in the pulmonary nodule care pathway. All patients enrolled in UConn';s pulmonary nodule clinic will be eligible. The number of subjects with data collection is unspecified and will depend on the number of patients seen during different phases of the study. The data collection will have three parts: Phase 1: Baseline pre-VNC installation: operational data will be extracted from patient charts up to 6 months prior to the ';Go live'; date of Optellum';s VNC at UConn. Ramp-up period: This is the period during which UConn VNC users are being trained and migrating from their existing workflow, while the VNC workflow is being customized to their feedback. Phase 2: Active Patient Discovery post-VNC installation: operational data will be collected for the 3-12 months post-installation of VNC. During this time the Patient Discovery feature of VNC will be in active use by UConn VNC users.
IRB No. 21-167SO-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. 24-125-1 (Dr. Archana Sanjay, PI): Analyzing the impact of aging on skeletal stem and progenitor cells in human bone marrow
This study will examine tissue biospecimens normally discarded from orthopaedic procedures to determine how aging impacts tissue on the cellular level. We plan to collect those discarded biospecimens and transfer them to the Musculoskeletal Institute Research Lab of Dr. Sanjay for preparation and analysis. Using these tissue biospecimens, we will attempt to understand and characterize the effects of aging on a cell's regenerative potential.
IRB No. 24-132-2 (Dr. Tarunya Vedere, PI): Primary Hyperaldosteronism is a Risk Factor for Developing Hypertensive Disorders of Pregnancy
This research is being done to determine if Primary Hyperaldosteronism (PA) is a pre-pregnancy risk factor for Hypertensive Disorders of Pregnancy (HDP). HDP which includes preeclampsia, eclampsia, gestational hypertension and chronic hypertension complicating pregnancy occur in about 10% of pregnancies and can cause a lifetime risk of developing chronic hypertension and heart disease. This study will look to see if excessive aldosterone hormone levels might be a risk factor for that. Aldosterone is a hormone naturally made in the body that helps keep the water and salt ratios in the body balanced. Excessive aldosterone hormone levels, or PA is a well-recognized cause of hypertension. Patients may be enrolled into the study or control group. Study group patients will have had a previous diagnosis of HDP in a pregnancy no earlier than January 1, 2018. Control group patients do not have any previous HDP diagnoses. Both groups will provide a one time blood draw, providing approximately 1 tablespoon of blood to be tested as well as one urine sample.
IRB No. 24-213-1 (Dr. Andrea Shields, PI): Development and Validation of a Non-Invasive Microbiome-Based Diagnostic Tool for Early Detection of Gestational Diabetes Mellitus
Gestational Diabetes Mellitus (GDM) is the development of glucose intolerance during pregnancy and is a serious complication with an incidence of 18% among pregnant people in the US. Recent evidence suggests that the gut microbiome undergoes changes parallel to GDM development early in pregnancy. This creates an important opportunity to establish a microbiome-based early screening tool to predict and potentially prevent GDM. Hypothesis/Question: Can a report containing risk scores for GDM based on proprietary stool collection from pregnant patients during their first trimester be developed to send to healthcare professionals promptly? Aims / objectives: We aim to develop a screening tool for the prediction of GDM as early as trimester 1 (T1) before the recommended administration of Oral Glucose Tolerance Test. Through non-invasive gut microbiome testing, we will determine T1 gut microbiome signatures associated with GDM and, based on these findings, develop an Machine Learning-based prediction model for GDM. This would allow for preventative treatment strategies before the disease becomes symptomatic and its side effects on the pregnant person and child become irreversible. The project aim is to demonstrate that the T1 maternal gut microbiome is a valid early indicator of GDM development, and an ML predictive model based on the microbiome';s characteristics permits accurate prediction of GDM development.
IRB No. 23-175HS-1 (Dr. Yanjiao Zhou, PI): Tracking the Microbiome Origin of Inflammation from Mouth to Placenta in Preeclampsia
AIMS Preeclampsia (PE) is defined by high blood pressure and proteinuria in pregnancy. It affects approximately 2-8% of the overall pregnant population and 17-25% of pregnant women with chronic hypertension. It is a leading cause of maternal death. Pathogenesis of PE involves excessive immune response, maternal endothelial dysfunction and abnormal placenta development. However, the initial factors responsible for the development of PE are unknown. Oral microbiota, comprising over 700 different bacterial species, has been linked not only to local periodontal diseases, but also systemic disorders. It has been speculated that oral microbiota can disseminate to placenta through blood circulation, heightening immune response and increasing risk of PE. Indeed, our recent work that tracked the oral and placental microbiome simultaneously in patients showed that the relative abundances of Haemophilus, Veillonella and Fusobacterium in subgingival plaque were significantly higher in patients with PE than matched controls without PE. We also rigorously identified the presence of these oral-like bacteria in placenta of PE patients, in contrast to controls. The preliminary data was based on samples collected at the delivery; thus, it is unclear whether the oral microbiome alteration is an acute process at PE onset or as a result of gradual alteration over the pregnancy term. It is also unclear when placental microbiome seeding occurs. A longitudinal profiling of the oral microbiome during pregnancy is critical to capture the overall dynamics of the microbiome in PE development, and provide novel insight into oral microbiome in pathogenesis of PE. Dysregulation of Th17/Tregs cells is a major contributor of pathogenesis of PE. Recent research showed that oral microbiome alteration in periodontal diseases can trigger Th17 cells to mediate oral mucosal immunopathology in an IL-6 dependent manner. Our preliminary data showed oral-like microbiota in placenta of PE patients were associated with elevated IL-6 in blood, raising a possibility that oral microbiome alteration may contribute to exaggerated immune response in PE through upregulation of IL-6 and Th17 cells. We hypothesize that an altered microbiome-immune interaction during pregnancy contributes to development of preeclampsia. We propose a prospective longitudinal study to determine dynamics of oral microbiome and immune response over different gestation and their association with PE. Aim 1. Determine the dynamics of the oral microbiome throughout pregnancy and their association with PE. We will prospectively enroll 100 patients with chronic hypertension or who meet criteria for being at risk of PE at UConn and Hartford Hospital. We will collect subgingival samples at each trimester and at PE onset, along with placenta at delivery. We will compare the oral microbiome of each trimester and at PE onset between patients who develop and who do not develop PE, and identify PE associated oral microbiome after controlling confounding factors. Placenta microbiome will be correlated with PE and oral microbiome. Aim 2. Determine the dynamics of immune response and immune-microbiome interactions throughout pregnancy. Blood will be collected at the same time as Aim1 in the study participants for immune assay. PBMC will be used to determine immune cell populations by flow cytometry focusing on Th17 and Tregs cells. Serum will be used to measure multiple panels of cytokines and chemokines by high- throughput Luminex assay. We will determine the association of oral microbiome at each trimester and placental microbiome with immune measures after controlling clinical confounding factors. Impact. The study holds promises to gain insight into the pathogenies of PE from a novel oral microbiome-immune interaction perspective, and lay ground work for future to develop non-invasive microbiome markers to predict PE. We will apply a R01 to extend the study to multi-centers to cross-validate the microbiome and immune findings. We also plan to collect and bank stool and vaginal samples from the study to create multiple lines of research on the microbiome and PE at Departments of Medicine and OB/GYN in future.
IRB No. 24-099J-1 (Dr. Timothy Crombleholme, PI): Intra-placental Gene Therapy with Ad-IGF-1 in BPH/5 mice with Mesenteric Uterine Artery Branch Ligation and Association of Pre-eclampsia and IUGR
Pre-eclampsia and hypertensive disorders of pregnancy present major health impact to both mother and fetus. Pre-eclampsia has been linked to maternal multi-organ failure, coagulopathic processes and in fetuses can impact fetal growth leading to growth restriction. The onset of pre-eclampsia is variable but typically onset is after 20 weeks of gestation. However, more severe forms of pre-eclampsia may present with earlier onset and have been linked to more egregious pregnancy complications, such as severe infantile uterine growth restriction (IUGR). Understanding the key mechanisms surrounding pre-eclampsia pathophysiology are vital to helping prevent and or cure this disease. Prior research has shown that the IGF-1 pathway is central in fetal growth and placental development. This project aims to study the pathophysiology of pre-eclampsia by studying the interrelation of IGF-1, a known common maternal and fetal pathway involved in cellular homeostasis. We will enroll mothers with pre-eclampsia, fetal growth restriction
IRB No. 25-160-2 (Dr. Hardeep Singh, PI): Recovery Kinetics Following Surgical Treatment for Degenerative L4-5 Spondylolisthesis: A pilot and Feasibility Study
Specific Aim(s) Evaluate recovery kinetics in patients undergoing lateral lumbar interbody fusion via prone approach + minimally invasive posterior spinal fusion (LLIF + PSF), minimally invasive transforaminal lumbar interbody fusion via tubular based retractor (MIS TLIF + PSF), and open transforaminal lumbar interbody fusion (Open TLIF + PSF) through monitoring step count during hospital stay and post operatively using a wearable fitness tracker. Compare length of stay, narcotic consumption, radiographic parameters, and fusion between groups outlined above.
IRB No. 24-186-1 (Dr. Francesco Celi, PI): Novel approaches to the treatment of hypothyroidism
The study’s goal is to closely examine this phenomenon and help patients reduce their body weight, serum cholesterol, and improve their quality of life. Eligible study participants are those who are 18 and over and on stable thyroid replacement therapy. They will receive free outpatient care for hypothyroidism, study medications, and thyroid hormone and cholesterol lipid analyses for the duration of the study.
IRB No. 25-016H-2 (Dr. Andrea Shields, PI): Bringing Residents, Fellows and Nurses Back to the Bedside to Support a Mother’s Road to Recovery: Interdisciplinary Trauma-Informed Care Curriculum for Perinatal Care
Physician recognition of impending trauma is highly important to prevent and mitigate possible patient distress. Pregnant women with a history of trauma and adverse childhood experiences can have higher levels of pregnancy related trauma which can exacerbate anxiety, depression, and PTSD symptoms. Trainees in OB/GYN and Labor and Delivery, including residents, fellows, and nurses, not only struggle with recognition of pregnancy-related trauma, but have experienced a higher level of burnout impacting the physician-patient relationship. Our goal is to improve recognition and management of pregnancy-related trauma while embodying a culture of mindfulness amongst OB/GYN residents, fellows, and nurse trainees.
IRB No. 24-158JO-2 (Dr. Julie Robison, PI): Skin immunity as a function of frailty, aging, and skin microbiome composition
Specific Aims AIM 1. Identify distinct and common skin immune features associated with aging and frailty-associated dysbiosis (FADS) to inform skin infection risk. AIM 2. Model how aging-related changes in skin infection response are modulated by the microbiome, senescence, inflammation, and genetic diversity. Design and Outcomes This is a prospective, observational, cohort study that will investigate how age-related declines in skin immunity relate to corresponding changes in the skin and its microbiome. Sample Size, Population, Interventions and Duration In this study, 42 participants ages 20-40 years old and 82 participants ages 60 years and older will be enrolled at the UConn Center on Aging in Farmington, CT and will participate in 2-4 study visits over 5 weeks. Visit 2 will occur the day after Visit 1. Visit 3 will occur 21 +/- 7 days after Visit 1 and Visit 4 the day after Visit 3. Skin (swab and micropatch at 7 skin sites) will be collected from participants to study the microbiome, immune profiling of interstitial fluid (ISF), and metabolomics. The seven skin sites will also be probed for skin physiologic metrics associated with frailty and aging.
IRB No. U25-159-1 (Dr. Ameer Rasheed, PI): A Randomized, Double-Blind, Placebo-Controlled, Phase 2b Study Evaluating the Safety and Efficacy of Pirfenidone Solution for Inhalation (AP01) in Subjects with Progressive Pulmonary Fibrosis (PPF)
The Sponsor is developing AP01 (also referred to in this document as the “study drug”) for use in the treatment of Progressive Pulmonary Fibrosis. AP01 is an experimental drug that we hypothesize may slow your PPF symptoms. You will inhale the study drug using the eFlow® Nebulizer System. The nebulizer used to deliver AP01 is approved in Europe, but is an investigational device for use in the United States and Canada (not approved by FDA or Health Canada).
IRB No. 24-111JSF-1 (Dr. Danielle Luciano, PI): The CT EndoRISE Biorepository
According to Connecticut Public Act No. 22-33, the CT EndoRISE biorepository will prospectively collect endometriosis tissues (termed lesions), healthy endometrium, blood, urine, and peritoneal fluid samples along with linked clinical and phenotypic data, symptoms, and quality of life questionnaires from patients with endometriosis and healthy controls. The CT EndoRISE is a collaboration between The Jackson Laboratory for Genomic Medicine and UConn Health.
IRB No. 25-198-2 (Dr. Andrea Shields, PI): Xenobiotic transfer of semaglutide using an ex vivo placental perfusion model: a pilot study
To our knowledge, there are limited studies that have researched if semaglutide has an effect on the placenta or if there is considerable transfer of the drug from maternal to fetal circulation. We propose studying the transfer of the drug on a single placental lobule of 7 placentas. We hypothesize that given the large molecular composition of semaglutide there will be minimal transfer of the drug in the ex-vivo placental perfusion model, thus providing safety data on the administration of semaglutide for therapeutic indications especially during pregnancy. The specific aims are: 1) To set up and troubleshoot the placental perfusion model using 3-5 placental lobules 2) To measure and compare the levels of therapeutic semaglutide in the maternal versus fetal perfusate collected from an ex-vivo placental perfusion model.
IRB No. 25-223-1 (Dr. Amanda Ulrich, PI): The Impact of vNOTES Hysterectomy on Sexual Function as Compared to Conventional Laparoscopic Hysterectomy and Robotic Assisted Laparoscopic Hysterectomy
This study aims to compare three different modalities of hysterectomy on female sexual function. vNOTES hysterectomy the newest surgical approach, will be compared to conventional minimally invasive and robotic assisted approaches. Pre- and post-operative surveys will be administered to assess female sexual function quantitatively using a validated survey called the female sexual function index. The change in this study from pre- op to 3-month and 6-months post-op will be compared between the 3 surgical approaches to determine if vNOTES hysterectomy has a negative impact on female sexual function.