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Clinical Trials: All
IRB No. 01-262-1 (Dr. Marion Frank, PI): Human Salty and Bitter Taste Mechanisms
Study description not available
IRB No. 02-016-1 (Dr. Robert Aseltine, PI): Pathways from Childhood Adversity to Adult Mental Health
Study description not available
IRB No. 02-200-1 (Dr. Bruce Liang, PI): Molecular Correlates of Atrial Fibrillation
Study description not available
IRB No. 02-288-2 (Dr. 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. 06-151-2 (Dr. Bruce Liang, PI): Circulating markers that underlie the transition from compensated hypertrophy to heart failure
Early detection and prevention are key features in treating subjects with heart failure. We are looking to see of caspase-3 and dystrophin can be detected in human circulation. If so, we will determine whether they are predictors for the transition between compensated and de-compensated heart failure.
IRB No. 07-016-1 (Dr. Martin Freilich, PI): Osteoporosis and bone augmentation/implant outcomes: An observational study
The objective of this study is to utilize a clinical study model to collect descriptive data needed to support the development of future studies that will test the association between specific measures of bone health and the successful integration of new bone from bone augmentation procedures. Postmenopausal women with a wide range of bone health and reduced jaw bone thickness will receive bone augmentation therapy followed by implant and restoration placement, with the specific treatment based upon best clinical judgment. Throughout initial diagnosis, treatment and follow-up, blood makrers will be drawn to assess bone health and its possible association with treatment outcomes. Outcomes will be based upon clinical and radiographic examination, bone health markers and patient interviews.
IRB No. 08-207-2 (Dr. Robert Arciero, PI): Multi-Center ACL Revision Study (MARS)
This is a multi-center, prospective, longitudinal, outcomes study with an invisted cohort group of participants undergoing ACL revisions, elective, standard of care (SOC) orthopedic knee surgery. Predictors of outcomes (QOL and premature osteoarthritis) have yet to be determined. The American Orthopaedic Society for Sports Medicine have set up, this multi-center evidenced based registry to recruit approximately 1,200 participants who will be followed out for 2-3 years.
IRB No. 07-252-2 (Dr. Bruce Liang, PI): Circulating Markers for Ischemic Heart Failure
The purpose of this research is to determine if two proteins in the blood are increased during acute myocardial infarction and whether their levels are higher in those who develop heart failure than those who do not. These two proteins are produced and potentially released when the heart muscle is damaged. They may then be released into the blood and be detected by standard method in the research laboratory. At this time, detection of an increase in these proteins in the blood is not know to be associated with any disease or myocardial infarction.
IRB No. 08-280-2 (Dr. Daniel Connor, PI): Assessment of Children in Outpatient Psychiatric Treatment
The study aims to analyze medical chart data from two child psychiatry outpatient clinics. The goal of the study is to learn about the characteristics and needs of children in outpatient psychiatric treatment and their families and who they respond to different forms of psychiatric and psychological treatment, in order to improve treatment services.
IRB No. 08-310-1 (Dr. Marilyn Sanders, PI): UCONN Health Center Research Tissue Registry/Repository
The objective of this project is to develop a research repository for the purpose of performing cancer studies. Information will be gathered form UCHC medical records, molecular and pathological analysis of blood collected and tissue gathered during surgical procedures. The tissue will be obtained during surgical procedures the patient may have elected to have performed at the Health Center in the future. The collection of data will also permit review of relevant information to identify patients who may be eligible for future studies, and to seek permission of patients to be contacted to determine their interest in taking part in future studies. De-identified information will be used for approved research studies and to gather pilot data for extra-mural grant applications.
IRB No. 1337-85-1 (Dr. Victor Hesselbrock, PI): (1) Neuroelectric Correlates of Risk for Alcohol Dependence (2) Deviance Proneness and the Risk for Alcohol Dependence
Study description not available
IRB No. 99-226-1 (Dr. Juan Salazar, PI): Cutanenous Immune Response in Secondary Syphilis and Lyme Disease
This study involved three separate sub-studies: 1) Lipopeptide injection: this component of the study demonstrated the contribution of synthetic lipopeptides in triggering the immune response in humans, these synthetic lipopeptides mimic spirochetal lipoproteins; 2) Secondary syphilis patients: this component of the study was conducted in order to better understand the pathogenesis of early syphilis and to determine how syphilis can set the stage for acquiring and transmitting HIV; 3) Healthy volunteer blood draw: These experiments are primarily conducted to study the effects of two spirochetes (Borrelia burgdorferi and Treponema pallidum). The only portion of the study that remains open is the healthy blood draw; the international and national sites have finalized their recruitment and no patients are being followed, data from these patients is currently under data analysis.
IRB No. 07-224-2 (Dr. Augustus Mazzocca, PI): The in vitro effect of biomaterials on human osteoblast, tenocytes and chondrocyte cultures
In this study the goal is to evaluate in vitro, biomaterials, using primary osteoblasts, tenocytes and chondrocytes abtained from discarded tissue samples during orthopaedic procedures.
IRB No. 11-027-2 (Dr. Susan Tannenbaum, PI): UCHC Cancer Center Research Screening
Study description not available
IRB No. 11-151-2 (Dr. Vincent Williams, PI): Hip and Knee Outcome Registry
Patients that have their hip or knees replaced by Dr. Williams or Dr. Lindsay have the option to enroll in the registry.
IRB No. 11-191-1 (Dr. Rajesh Lalla, PI): Quality Assessment of Pre-Radiation Dental Management in Head and Neck Cancer Patients
Oral Medicine Quality Assurance Study
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. 11-157-3 (Dr. Bruce Liang, PI): Circulating Caspase-3 p17 Fragment as a Novel Marker for Cardiac Apotosis
This study is an investigator initiated prospective longitudinal follow-up study with two arms (Acute STEMI subjects and Bypass surgery subjects) and collection of DNA samples. The project plans to test the hypothesis that cardiac cells undergo cell death (apoptosis) in patients during ischemic/reperfusion (I/R), and to ultimately determine the clinical significance of such cell death. By establishing the presence and importance of cardiac myocyte apoptosis the study outcomes intends to provide the rationale for developing anti-apoptotic therapy for clinically relevant I/R conditions. The research aims are to 1) Determine existence of human cardiac myocyte apoptosis under two clinically relevant ischemia/reperfusion conditions, acute ST segment elevation myocardial infarction (STEMI) with primary percutaneous coronary intervention (PCI) and cardioplegia (cardiac muscle paralysis) for bypass surgery 2) Determine the potential clinical significance of coronary and peripheral venous levels of p17 during acute STEMI with PCI and during cardioplegiaa. 68 subjects from UCHC cardiology patient base are expected to be enrolled in this study, 34 patients with anterior STEMI and 34 patients undergoing cardio-pulmonary bypass surgery. Once blood samples are obtained from each group medical records will be reviewed or follow-up calls will be made twice a year for three years to update any new cardiac events. There is no compensation to subjects participating.
IRB No. 11-168-1 (Dr. Lawrence Engmann, PI): A Prospective Comparison of Transcriptional Profiling of Luteal Phase Endometrial Biopsies After Ovarian Stimulation with Gonadotropins and Induction of Oocyte Maturation with a Gonadotropin Releasing Hormone (GnRH) Agonist or Human Chorionic Gonadotropins (hCG)
The purpose of the study is to compare gene expression profiles in endometrial biopsies taken during the window of implantation after triggers of oocyte maturation using GnRH agonist or hCG. The hypothesis is that the reduced rate of embryo implantation in some women triggered with GnRH agonist is due to alter gene expression in the endometrium.
IRB No. 10-273SFS-2 (Dr. Robert Clark, PI): The Role of Unique Lipids Derived From Common Human Bacteria in Multiple Sclerosis
Study description not available
IRB No. 12-188-2 (Dr. George Kuchel, PI): Impact of Aging T Cell Responses to Influenza Vaccination
Participate in our research study on the immune system looking at how we can use vaccines to protect us against infections. With aging, that system does not function as well. We think this research will provide information that could eventually lead to more effective vaccines for preventing influenza illness and potentially other infectious diseases in older people. Men and Women must be 20-30 years old OR 50 years of age and Older; Have been vaccinated in last year, but not for current flu season; Do not have any Immunosuppressive diseases or on any Immunosuppressive therapy. Participants must be willing to come in for 4 study visits where blood will be drawn at 3 visits. Standard Flu vaccinations will be given as part of the study at no charge. Monetary compensation will be provided.
IRB No. 13-061-6 (Dr. Biree Andemariam, PI): CASIRE Sickle Cell Renal Disease Cohort International Study Protocol
Study description not available
IRB No. 13-119-2 (Dr. Bruce Liang, PI): Study of Circulating Monocytes in Patients with Coronary Artery Disease
Study description not available
IRB No. 14-024-2 (Dr. Adam Adler, PI): In vitro characterization of cancer related immune impairment and its reversal by the use of cytokines, costimulatory molecules and a blocker of immune suppression used singly or in combination
The trial will include patients with advanced malignancy and an estimated survival of 6 months or less, based on the judgment of their oncologist, the type of malignancy, ECOG performance status, stage of disease and pre-existing co-morbidities. This is an exploratory in-vitro study which is being performed to determine optimal combinations of cytokines, costimulatory agonists and inhibitors of immune-suppressive factors to restore immune responsiveness in patients with advanced malignancy. Patients meeting the “inclusion and exclusion criteria” will be solicited by their physician or designee to allow a venipuncture and withdrawal of 20cc of blood. The samples will be obtained, as much as feasible, along with routine blood work, so as to minimize the need for additional venipuncture. The lymphocytes will be isolated and exposed to cytokines, including, but not limited to, members of the IL1 family of cytokines [IL 1, IL 18, and IL 33. IL 36]. The cells will also be exposed to agonists for costimulatory molecules of the TNF family, including but not limited to, OX-40 and 4-1-BB. Costimulatory agonists and antagonists to B7 family will also be used, including but not limited to PD1, PD2, PD1L and CD28. An inhibitor of IDO will also be used to reduce the suppressive effects of Tregs and MDSC. The T-cells will be stimulated by vaccine recall antigens, such as tetanus toxoid and influenza antigen. Mitogens such as PMA plus Ionomycin and/or anti-CD3 monoclonal antibody will also be employed. Ki-67 staining, a marker of cell proliferation will be done to determine a Ki-67 labeling index on the study and control specimens before and after experimental manipulations. Measurements of T cell cytotoxicity and quantification of expression levels of cytotoxic effector molecules will be performed before and after experimental manipulations. RNA-Seq will be done before and after experimental manipulations of the study and control specimens to determine which genes are being transcribed in response to experimental measures. Control samples will be obtained from de-identified blood purchased from the GRC. These control specimens will be stimulated and activated in a similar fashion to the specimens obtained from the experimental subjects. If possible, the same study patients will be requested to allow a second venipuncture no sooner than 6 weeks after the first venipuncture, and in no case, no sooner than six weeks after the last antineoplastic therapy.
IRB No. 14-056-6 (Dr. Pamela Taxel, PI): Investigation of the Ability of the UCONNS (University of Connecticut OsteoNecrosis Numerical Scale) to Predict the Risk for the Developing Osteonecrosis of the Jaw in Women Receiving Bone-Modifying Therapies for Cancer
The purpose of this proposal is to investigate the risk factors for osteonecrosis of the jaw (ONJ), a known complication of several bone-modifying therapies used in the treatment of advanced cancers. When this complication occurs, it can lead to the discontinuation of important therapy that often impacts the quality of life in skeletal-related events in this population. With the use of a weighted scale that we have devised, the University of Connecticut OsteoNecrosis Numerical Scale (UCONNS), based on known risk factors for ONJ, we aim to validate this scale as a potential predictor of patients at risk, so they may be appropriately monitored and preventative treatment can be initiated. As the medical community has limited guidelines regarding ONJ, we anticipate that this scale, if validated, will foster better communication among providers, as well as improve patient outcomes. This proposal represents a unique collaboration between two investigators in the dental and medical schools at the University of Connecticut Health Center. We hypothesize that the UCONNS can aid in the identification of cancer patients who may be at increased risk for the development of ONJ associated with the use of bisphosphonates and the newer bone modifying therapy, denosumab.
IRB No. 14-057-6 (Dr. Pamela Taxel, PI): Investigation of the Ability of the UCONNS (University of Connecticut OsteoNecrosis Numerical Scale) to Predict the Risk for the Developing Osteonecrosis of the Jaw in Women Receiving Bone-Modifying Therapies for Breast Cancer
The aim of this proprosal is to investigate the risk factors for Osteonecrosis of the Jaws (ONJ), a known complication of several bone-modifying therapies including bisphosphonates and denosumab, a human monoclonal antibody. ONJ is most commonly seen with the use of these medications in the treatment of skeletal related events in cancer patients with metastatic bone disease, and less frequently seen in the treatment of osteoporosis. This complication often causes significant effects on quality of life that may lead to the discontinuation of important disease-modifying therapy. We have recently developed the UCONNS (University of Connecticut OsteoNecrosis Scale) a weighted scale based on known medical and dental risk factors for ONJ that we are currently validating both retrospectively and prospectively for use as a potential predictor of patients at risk, so they may be appropriately monitored and preventative treatment can be initiated. The current proposal aims to add to the UCONNS by prospectively measuring serum bone markers that may prove valuable in predicting patients that are at increased risk for developing ONJ. We will follow patients who are being treated with bone modifying agents in order to prospectively measure and evaluate a panel of unique parameters of bone metabolism to identify potentially predictive serum biomarkers for the development of ONJ. We hypothesize that the UCONNS can aid in the identification of breast cancer patients who may be at increased risk for the development of ONJ associated with the use of bisphosphonates and the newer bone modifying therapy, denosumab.
IRB No. 09-185J-2 (Dr. Upendra Hegde, PI): TCR Engineered T Cells in Tumor Immunity
simple blood draw. no risk to study subject.
IRB No. 14-107-6 (Dr. Biree Andemariam, PI): Identification of Patient-specific RBC-endothelial Cell Adhesion Profiles as Markers of Sickle Cell Disease Severity.
The research objective of this proposal is to determine in 25 adult/pediatric SCD patients (1) the relationship between pain severity phenotype and the strength of adhesion between single red blood cells (RBCs) and single endothelial cells (ECs) isolated from peripheral blood and (2) the ex vivo effect of pharmacologic inhibitors on RBC-EC adhesion, creating both a patient-specific adhesion profile and therapeutic signature. The results are expected to lead to novel individually-targeted approaches to inhibit the onset and limit the duration of painful vaso-occlusive episodes (VOEs). Our central hypothesis is that the strength of adhesion between RBCs and ECs at baseline is related to patient-specific pain severity phenotype, resulting in the need for patient-specific drug therapy. To test the hypothesis, we will pursue the following three specific aims: Investigate the relationship between pain severity phenotype and baseline RBC-EC adhesion profile in SCD subjects – We will measure the strength of adhesion between single RBCs-ECs from SCD subjects at baseline. Baseline/steady-state adhesion profiles will be compared on an inter-patient level to determine which adhesion profiles correlate most highly with pain severity phenotype. Assess the association of VOE severity with changes in RBC-EC adhesion from baseline to VOE onset. We will measure the change in strength of adhesion between single RBCs-ECs from baseline to VOE onset. Changes in adhesion will be compared on an inter-patient level to determine whether relative changes in adhesion profile at VOE onset correlate with VOE severity. Test the ex vivo effect of targeted pharmacotherapy on the RBC-EC adhesion profile of SCD subjects – We will measure (at baseline and at VOE onset) the ex vivo inhibitory effect of two known RBC-EC adhesion blockers (propranolol and abciximab) to identify patient-specific anti-adhesive therapeutic signatures.
IRB No. 14-136-6 (Dr. Biree Andemariam, PI): Hemoglobinopathies and Bone Health
This research study has two purposes. The first purpose is to determine whether having sickle cell trait is a risk factor for the development of bone thinning at an earlier age than expected. Nearly 10% of African Americans carry sickle cell trait and most of them are unaware of it. African Americans are less likely to develop thin bones than whites, but if they sustain a bone fracture, they are more likely to die from it. We believe having sickle cell trait may lead to bone thinning and predispose a subset of African Americans to dangerously thin bones. The second purpose is to try to understand why individuals with sickle cell disease have thinner bones than healthy individuals do. Doctors have already discovered that people with sickle cell disease have very thin bones, but they have not determined why. Our study will try to identify whether the bone thinning is from the body not making enough bone or from the body losing bone once it is made.
IRB No. 14-179-1 (Dr. Rajesh Lalla, PI): Oral Microbiome in Head and Neck Cancer Patients
This research study is about the community of germs that live in the mouth (the oral microbiome) and its relationship to oral complications of radiation therapy such as dryness, mouth sores, tooth loss, cavities, gum disease or poor healing of bone. The purpose of this study is to look at changes in the oral microbiome from before radiation therapy until 18 months after radiation therapy to see if certain characteristics of the oral microbiome relate to mouth problems that may occur after radiation therapy. An optional sub-study is about future genetic testing of saliva samples to look for genes that may affect the risk of oral complications of radiation therapy..
IRB No. 15-027-2 (Dr. Susan Tannenbaum, PI): S1207, "Phase III Randomized, Placebo-Controlled Clinical Trial Evaluating the Use of Adjuvant Endocrine Therapy +/- One Year of Everolimus in Patients with High-Risk, Hormone Receptor-Positive and HER2/neuNegative Breast Cancer."
Primary Objective: The primary objective of this study is to compare whether the addition of one year of everolimus (10 mg daily) to standard adjuvant endocrine therapy improves invasive disease-free survival (IDFS) in patients with high-risk, hormone-receptor (HR) positive and HER2-negative breast cancer. Secondary Objectives: a. To compare whether the addition of one year of everolimus to standard adjuvant endocrine therapy improves overall survival (OS) and distant recurrence-free survival (DRFS) in this patient population. b. To evaluate the safety, toxicities and tolerability of one year of everolimus in combination with standard adjuvant endocrine therapy and compare it with standard adjuvant endocrine therapy plus placebo in this patient population. c. To determine whether the benefit of one year of everolimus use in addition to standard adjuvant endocrine therapy varies by recurrence score (RS), nodal status, or other commonly used prognostic factors. d. To evaluate adherence to 1-year treatment of everolimus in comparison to placebo in addition to standard adjuvant endocrine therapy in this patient population. e. To collect specimens in order to evaluate biomarkers of therapeutic efficacy.
IRB No. 09-156H-1 (Dr. Carla Rash, PI): Reward Center
Study description not available
IRB No. 15-077-1 (Dr. Susan Tannenbaum, PI): A Phase 1/2 Study Exploring the Safety, Tolerability, and Efficacy of MK-3475 in Combination with INCB024360 in Subjects with Selected Solid Tumors (Phase 1) Followed by a Randomized, Double-Blind, Placebo-Controlled Study in Subjects with Advanced Non-Small Cell Lung Cancer (Phase 2)
The INCB 24360-202 study is a randomized, double-blind, placebo-controlled Phase 1/2 study of INCB024360 or placebo administered in combination with MK-3475. Phase 1 will be open-label and will include subjects with Stage IIIB, IV, or recurrent non--small cell lung cancer (NSCLC), melanoma, transitional carcinoma of the genitourinary (GU) tract, renal cell cancer, triple negative breast cancer, adenocarcinoma of the endometrium, or squamous cell carcinoma of the head and neck, and Phase 2 will be randomized, double-blind, and placebo-controlled in subjects with Stage IIIB, IV, or recurrent NSCLC. INCB024360 represents a novel, potent, and selective inhibitor of the enzyme indoleamine 2,3 dioxygenase-1 (IDO1) in both human tumor cells and human dendritic cells (DCs). MK-3475 is a potent and highly selective humanized monoclonal antibody of the immunoglobulin (Ig) G4/kappa isotype directed against programmed death receptor 1 (PD-1). For a thorough discussion of the pharmacology of MK-3475 and INCB024360, refer to the INCB024360 Investigator’s Brochure (iIB) and the MK-3475 Investigator’s Brochure (mIB). The goal of cancer immunotherapy is to initiate or reinitiate a self-sustaining cycle of cancer immunity, enabling it to amplify and propagate. Cancer immunotherapies must overcome the negative feedback mechanisms inherent in most cancers. The current approach will attempt to further amplify an immune response by targeting multiple nonredundant immune checkpoints. Expression of IDO1 represents an early checkpoint that results in a diminished immune response and tolerance to tumor antigen. Many recent clinical results suggest that another common rate-limiting step is the expression of PD-L1 as a distal immune modulator expressed in 20% to 50% of human cancer (Hiraoka 2010, Herbst et al 2013), including but not limited to the ones selected for investigation in the Phase 1 portion of this study: advanced or metastatic NSCLC, melanoma, transitional carcinoma of the GU tract, renal cell cancer, triple negative breast cancer, endometrial cancer, or squamous cell carcinoma of the head and neck. Expression of IDO and PD-1/L1 have been found to be increased in NSCLC as the disease progresses, and expression of these markers in tumor cells has been associated with shorter subject survival (Iversen et al 2013). Anti-PD-L1 and anti-PD-1 monotherapy response rates of 17% to 24% have been reported in refractory NSCLC (Garon et al 2013, Brahmer et al 2013) with survival medians of 8 to 18 months; however, MK-3475 has not yet reached the median in its study (Garon et al 2013). Thus, there is a strong rationale for therapies aimed at restoring antitumor immunocompetence in NSCLC and establishing a rationale for inhibiting IDO1 and the PD-1/L1 pathways in this disease. 2. STUDY OBJECTIVES AND PURPOSE 2.1. Primary Objectives ? Phase 1: To evaluate the safety, tolerability, and DLTs of a pharmacologically active dose (PAD) of INCB024360 administered in combination with MK-3475 in advanced or metastatic solid tumors, and to select doses for further evaluation. ? Phase 2: To evaluate and compare the PFS of subjects with Stage IIIB, IV, or recurrent NSCLC when treated with INCB024360 in combination with MK-3475 versus MK-3475 alone as determined by investigator assessment of objective radiographic disease assessments per modified RECIST v1.1. 2.2. Secondary Objectives (Phase 2) ? To evaluate and compare the efficacy of the 2 treatment groups with respect to ORR utilizing modified RECIST v1.1 ? To evaluate and compare the efficacy of the 2 treatment groups with respect to ordinal categorical response score, calculated as the following: - 1 = Complete response per modified RECIST v1.1 - 2 = Very good response, defined as > 60% tumor reduction - 3 = Minor response, defined as > 30% to 60% tumor reduction
IRB No. 15-157-6 (Dr. Golda Ginsburg, PI): Unified Treatment of Emotional Disorders in Community Clinics
Emotional disorders, encompassing a range of anxiety and depressive disorders, are the most prevalent and comorbid psychiatric disorders in adolescence. Evidence-based therapies (EBTs) exist for single disorders (e.g., depression) or small clusters of disorders (e.g., anxiety disorders) but such EBTs are rarely integrated in community mental health clinic (CMHC) settings and effect sizes are modest (40-50% of youth are treatment non-responders). Thus, methods for improving outcomes for these youth, particularly in CMHCs, are needed. Transdiagnostic treatment, such as the Unified Protocols for the Treatment of Emotional Disorders in adults (UP), adolescents (UP-A) and children (UP-C) is a promising new approach that uses a small number of common strategies to treat these conditions. Another novel approach to improving clinical outcomes for youth with emotional disorders in CMHCs is the incorporation of a standardized measurement and feedback system (MFS). Emerging data suggests that MFS alone improves outcomes relative to treatment as usual (TAU) but this has not been adequately tested in youth. Thus, our first aim is to examine the effectiveness of UP-A and a MFS relative to TAU, when delivered in CMHCs. A serious shortcoming of RCTs comparing EBTs to TAU is the confounding effects of increased measurement and feedback to clinicians as RCTs of EBTs often “build in” monitoring that is not part of standard care. This raises the possibility that increased monitoring, rather than the unique treatment components of the EBT, may be responsible for better outcomes over TAU. Thus, the second aim of this proposal is to isolate these effects from UP-A. Finally, this study will examine theoretically-linked mechanisms (both patient and provider level) of treatment outcomes of both the UP-A and the Youth Outcomes Questionnaire (YOQ). This project is an NIMH-funded collaborative R01 two -site trial (UM grant PIs Jill Ehrenreich-May and Amanda Jensen-Doss; University of Connecticut PI Golda Ginsburg - for IRB purposes, the UM PI will be Amanda Jensen-Doss). To address the three study aims, adolescents with anxiety and/or depressive disorders will be recruited from CMHCs in Miami and in CT (under the supervision of Dr. Golda Ginsburg at the University of Connecticut). Both adolescents and clinicians will be randomized to one of three conditions: (1) TAU alone; (2) TAU plus YOQ (TAU+); and (3) UP-A plus YOQ (UP-A). Research assessments by Independent Evaluators (IEs), children, parents, and clinicians will occur at baseline, 8 weeks and 16 weeks after treatment initiation and a 3-month follow-up. The primary aims of this study are as follows: Aim 1: To examine the effectiveness of UP-A and YOQ compared to TAU. Aim 1 will test whether adolescents treated with UP-A and YOQ (plus TAU referred to as TAU +) demonstrate better response than those receiving TAU alone. Hypothesis 1: A higher percent of adolescents treated with UP-A and TAU +, compared to TAU, will be treatment responders at 16 weeks after treatment initiation and at follow-up. Aim 2: To isolate the effects of evidenced-based measurement and feedback. Aim 2 will examine the relative effectiveness of the UP-A condition to the TAU+ condition. Hypothesis 2: A higher percent of UP-A participants will be treatment responders than TAU+ participants at the 16 week and follow up assessments. Aim 3: To examine mechanisms theoretically associated with UP-A and YOQ. Hypothesis 3a: Differences in outcomes between the UP-A and the other two conditions will be mediated by changes in: Emotional Reactivity and Regulation (Using the Reactivity and Regulation-Images Task, REAR-I) and Behavioral Avoidance (using the Avoidance Hierarchy).
IRB No. 16-055-2 (Dr. David Steffens, PI): Department of Psychiatry: Adult Repository
The purpose of the repository is to prospectively collect biological samples along with clinical data to facilitate future research studies and pilot analysis related to medical and behavioral health research.
IRB No. 16-124-1 (Dr. Upendra Hegde, PI): A Prospectively Designed Study to Assess the Relationship between Tumor Mutation Burden and Predicted Neo-antigen Burden in Patients with Advanced Melanoma or Bladder Cancer Treated with Nivolumab or Nivolumab plus Ipilimumab (CA209-260)
A Prospectively Designed Study to Assess the Relationship between Tumor Mutation Burden and Predicted Neo-antigen Burden in Patients with Advanced Melanoma or Bladder Cancer Treated with Nivolumab or Nivolumab plus Ipilimumab (CA209-260) Background and rationale: Please refer to section 3.0 of the Protocol Study design: This is a prospectively designed, open label study. It includes 2 independent study populations (melanoma and bladder) Study population and sample size: Patients with histologically confirmed locally advanced or metastatic disease of the following tumor types who meet the eligibility criteria: 1. melanoma and 2. bladder cancer. 120 evaluable patients will be enrolled in two separate arms. In each arm, 60 evaluable patients will be enrolled. Major study interventions: All eligible patients with melanoma will receive ipilimumab at a dose of 3mg/kg combined with nivolumab at a dose of 1mg/kg. The ipilimumab and nivolumab will be dosed every 3 weeks for 4 doses. Thereafter, patients may be eligible to receive nivolumab monotherapy at a dose of 3mg/kg administered every 2 weeks for up to 2 years. All eligible patients with bladder cancer will receive nivolumab at a dose of 3mg/kg administered every 2 weeks for up to 2 years. Patients with bladder cancer who have confirmed disease progression after treatment with nivolumab monotherapy may be treated with the combination of nivolumab and ipilimumab. Main outcome measures/analyses: Please refer to section 2.0 of the Protocol
IRB No. 16-220-1 (Dr. Jonathan Covault, PI): A Phase I Study of the Biomarker Response and Pharmacokinetic Profile of Thyrotropin-Releasing Hormone (TRH) Administered as a Sublingual Tablet
This present study will compare effects (both good and bad) of two doses of sublingual Thyrotropin releasing hormone (TRH) tablets, to the standard i.v. dose of TRH and, for comparison, to a tablet of TRH that is meant to be swallowed rather than dissolved under the tongue. The two primary measures that will be evaluated in healthy volunteers are: 1. The classic response to TRH, which is measured as the increase in the hormone thyrotropin (TSH) from baseline levels to the peak level achieved following administration of TRH. 2. The pharmacokinetic (the way the body absorbs, distributes and gets rid of a drug) profile of TRH in blood plasma after sublingual tablet administration. Additional goals of the present study include assessment of selected behavioral measures after TRH administration by the sublingual, i.v. and regular oral tablet routes, determination of changes in selected measures of immune system function, and evaluation of physiological (pulse, blood pressure and EKG) measures and reports of any side effects observed following administration of the different TRH formulations. Objectives: 1. To compare the biomarker response (i.e., the TSH response) after administration of TRH by intravenous injection (0.5 mg), after two doses of a sublingual TRH tablet formulation (0.5 mg and 5 mg), and after administration of a standard oral tablet formulation of TRH (5 mg). 2. To determine the pharmacokinetic profile of TRH administered by intravenous, sublingual tablet and oral tablet formulations, as assessed by determination of plasma TRH concentration at specified times over a 180 minute period of evaluation. 3. To evaluate the tolerability of TRH administered by intravenous, sublingual and standard oral tablet formulations as determined by assessment of vital signs, laboratory measures and subject reports of adverse effects. 4. To collect samples to carry out assessments of effects of TRH administered by intravenous, sublingual tablet and oral tablet formulations on selected indices of immune system function and behavioral responses for which future funding is being sought. Study Hypothesis: The central hypothesis of the present study is that a unique sublingual tablet formulation of TRH, developed by Dr. Bogner at the UConn School of Pharmacy and demonstrated to show promising enhancement of lipophilicity based on in vitro laboratory assessments, will provide suitable bioavailability when administered to normal human subjects. For appropriately selected compounds, sublingual administration can avoid problems related to poor absorption in the GI tract, metabolism by enzymes at the level of the intestinal membrane wall, and the hepatic first-pass effect (Goswami et al., 2008). Compounds with suitable lipophilicity can permeate the sublingual epithelial cell layer and reach the underlying connective tissue layer, which is highly vascularized. Via this route, appropriately selected compounds can gain efficient access to the general circulation and demonstrate good bioavailability in plasma, thus supporting therapeutic application after sublingual tablet administration. Previous in vitro studies in Dr. Bogner's laboratory documented a greater than 100-fold increase in lipophilicity for the novel TRH formulation, thus predicting the likelihood of suitable bioavailability associated with sublingual tablet administration in human subjects. The proposed Phase I study will document that administration of the optimized sublingual TRH tablet formulation produces the classic biomarker response to TRH and will also delineate the pharmacokinetic profile of TRH in plasma following sublingual tablet administration.
IRB No. 16-234-1 (Dr. Bruce Liang, PI): UConn Health Cardiology Center Research Screening Protocol
This protocol will be used to gain permission from cardiology patients for Cardiology research staff to access health medical records in order to determine eligibility for research studies and clinical trials. The protocol does not involve actual scientific research.
IRB No. 01-127H-2 (Dr. Kazuya Machida, PI): Signalosome-oriented Phosphotyrosine Profiling of B-cell Malignancies
Study description not available
IRB No. 17-070-1 (Dr. Robert Arciero, PI): Mid and Long Term Outcomes of Anterior Shoulder Instability after Arthroscopic Stabilization
The purpose of this study is to assess outcomes at 5 years or more in patients who have undergone an arthroscopic stabilization for symptomatic unidirectional anterior shoulder instability. A survey will be used to collect updated postoperative outcome information from patients regarding current pain, satisfaction and functional outcomes. A chart review will be conducted to collect demographic, injury and perioperative details. These factors will be combined to examine correlations with outcomes.
IRB No. 17-072-6 (Dr. Damion Grasso, PI): Adaptation and Resilience in Childhood Study (ARCS)
In the current application we propose applying advances in developmental measurement science, including those developed in our own lab, towards sensitive characterization of DV 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 experiencing an acute stage of DV exposure in which mother and child are receiving services at a DV shelter. 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 and autonomic (heart rate, skin conductance) responses to laboratory-based threat stimuli, and (5) observed and reported maternal sensitivity and parent-child interaction. We also will apply a semi-structured, timeline follow-back approach in the mother interviews, which we have developed, to assess and characterize children's peritraumatic responses (i.e., during and/or immediately after the exposure) to DV, which our preliminary data suggests may be predictive of PTS symptoms. In the current project, families will be recruited from nearby DV shelters. Research visits will occur at our newly established early child development laboratory on the UConn Kane Street property in West Hartford and will last approximately four hours. Families will be compensated for their time. Specific Aims: Aim 1. To employ a multi-method assessment approach towards examining links between DV exposure, peritraumatic behavioral responses, and PTS symptoms in shelter-residing preschool age children recently exposed to DV. Aim 2. To examine associations between multiple indices of behavioral and physiological threat detection and reactivity (i.e., attention bias to threat, observed fear/anxiety, and autonomic reactivity) and trauma-related symptoms. Aim 3. To identify factors in the caregiving environment that appear to buffer or potentiate trauma-related symptoms and associated patterns of threat detection and reactivity.
IRB No. 14-194J-3.2 (Dr. George Kuchel, PI): Impact of aging on gene expression and RNA splice variants in peripheral blood cells
PRIMARY HYPOTHESIS We will be able to gain a comprehensive view of the genomic alterations associated with aging and frailty using immunological and system biology approaches. Furthermore, we theorize that these changes will be associated with specific microbiome composition. SPECIFIC AIMS This is a single-center exploratory study to carry out transcriptional and microbiome profiling analysis to gain a comprehensive view of genomic alterations associated with aging and frailty. Aim 1: To collect the samples from well-characterized volunteer cohorts. Aim 2: To establish whole blood isoform profiles. Aim 3: To establish epigenetic profiles of PBMCs and sorted blood cells Aim 4: To characterize microbiome in saliva and stool samples. Aim 5: To devise informatics methods to uncover the dynamics of transcriptional regulatory program associated with pathologies in human cells, in particular with the aging of immune cells. Aim 6: To evaluate epigenetic data using developed algorithms to address the following questions: 6a: Which regulatory programs and regulatory interactions are disrupted with aging and in which immune cells? 6b. How do men and women age differently based on transcriptional data (sex effects)? 6c. What are the putative genomic/clinical/immunological markers of healthy aging? SIGNIFICANCE It becomes critically important to apply system biology approaches and in-depth genomics to understand aging and related alterations. Identifying the immunologic parameters that correlate with or predict immune alterations will have a significant impact on the increased understanding of disease physiology in older age and eventually novel biomarkers and targets for therapy. RELEVANCE Recent technological breakthroughs have made the study of biological systems on a large scale a reality, thus offering unprecedented opportunities to comprehensively profile genome and immune responses in human subjects. A major challenge when engaging in such studies is to establish baseline values in subjects over time under "healthy" conditions. This data will be used as a basis for design of futures studies identifying changes occurring in response to challenge as for example acute infection or vaccination.
IRB No. 15-073-3.2 (Dr. Agnes Kim, PI): Circulating Biomarkers and Noninvasive Cardiac Imaging Techniques That predict Cancer Therapy Cardiotoxicity
The primary goal of this pilot study is to identify early signs of cardiotoxicity in patients with a wide range of cancers who are treated with anthracycline chemotherapy, alone or in conjunction with other chemotherapeutic or molecularly targeted cancer drugs, before there is irreversible cardiac dysfunction or clinical heart failure. We hypothesize that an elevation in apoptotic and inflammatory biomarkers and early changes in myocardial deformation as measured by strain imaging after exposure to anthracycline chemotherapy predict future development of cardiac dysfunction. By checking the levels of these biomarkers before chemotherapy, then at 3 months and at one year in cancer patients receiving anthracyclines, our goal is to determine whether those patients with a ""spike"" in level develop left ventricular dysfunction and/or clinical heart failure. Similarly, strain imaging by echocardiography will be performed at baseline, then every 3 months and at one year. We hypothesize that a decrease in global longitudinal strain can predict future reduction in LVEF. Our goal is to identify early those patients who are at a high risk for anthracycline-related cardiac toxicity. Early identification may lead to early institution of cardioprotective therapies (i.e. beta blockers and ACE inhibitors), which may prevent irreversible cardiac dysfunction and clinical congestive heart failure. Objectives: To determine the potential utility of biomarkers for the early identification of patients with cancer who are at risk for cardiac dysfunction. To determine whether biomarker levels, or serial changes in biomarker levels, or combination of biomarkers (activated caspase-3, troponin I, IL-6, TNF alpha, CRP, caspase-1, BNP) could predict subsequent cardiotoxicity in patients treated with anthracycline chemotherapy. To determine the utility of strain imaging in the identification of early cardiotoxicity. To determine whether cleaved caspase-3 and caspase-1 show serial changes over time during the course of cancer treatment with chemotherapy. Hypotheses: A serial increase in biomarker levels from baseline to post-chemotherapy may predict subsequent development of systolic or diastolic cardiac dysfunction. Caspase-3 as an apoptotic marker, caspase-1 as an inflammatory marker upstream of IL-1beta, IL-6 and CRP, and troponin I as cardiac injury marker can be quantified in human circulation. An elevation in the levels of these markers may indicate anthracycline-related cardiac apoptosis/ injury and associated inflammation. Strain imaging by echocardiography can identify early sub-clinical imaging evidence of cardiotoxicity. Taken together, the advanced strain imaging and novel biomarkers may identify those who are at risk of developing clinical cardiac dysfunction or heart failure. In the future, we will test whether prevention of overt heart failure can be achieved by institution of medications such as beta blocker and angiotensin converting enzyme inhibitor or angiotensin receptor blocker in these at-risk individuals.
IRB No. 17-013-6 (Dr. Susan Tannenbaum, PI): Retrospective study to investigate clinical utility of BIOARRAY Therapeutics genomic panel as a predictor of pathological response in breast cancer patients treated with taxane-based neoadjuvant chemotherapy as well as in patients who have developed metastatic disease.
In our study we are partnering with BIOARRAY Therapeutics. It is a biotechnology company that has developed a genomic profiling test based algorithm. This algorithm can predict response in breast cancer patients when treated with taxane-based chemotherapy. This information can help physicians personalize treatments upfront. The goal of this study is to validate using retrospective samples, the ability to predict response based on their BIOARRAY test profile.
IRB No. 18-082-2 (Dr. Anthony Parrino, PI): Early Mobilization After Thumb (Carpometacarpal) Arthroplasty
The purpose of this research study is to determine the best post-operative therapy after a thumb (carpometacarpal or CMC) arthroplasty. Patients are currently placed in a thumb splint for 4 weeks after their thumb surgery. However, new research has questioned whether 4 weeks of splinting is needed. Our study will compare patients’ outcomes between 2 groups. One group will be placed in a splint for approximately 10 days after surgery and the other group will be in a splint for the normal duration after surgery (about 4 weeks).
IRB No. 17-155-3 (Dr. Adam Lindsay, PI): Fundamentals of Orthopaedic Surgery (FORS) & Fundamentals of Arthroscopic Techniques (FAST) Surgical Simulators
The purpose of this research study is to evaluate two surgical simulators as a way of assessing and improving surgical skills. The simulators are composed of materials founds at hardware stores such as PVC pipes, pipe insulation, foam bricks and wood blocks. Participants will be asked to perform different surgical skills such as suturing, drilling and/or arthroscopy using one or both of the simulators while being observed. Participation involves multiple 20-30 minute testing sessions to evaluate surgical skills over time. The following individuals are invited to participate in this study: • All UConn Medical Students • All UConn Medical Residents • All UConn Medical Fellows • Attending Physicians that perform more than 5 orthopaedic surgery/arthroscopic operations per month
IRB No. 13-087-3.2 (Dr. Susan Tannenbaum, PI): Factors Influencing Fatigue in Breast Cancer Patients Undergoing Breast Irradiation
Study description not available
IRB No. 12-013S-3.2 (Dr. Biree Andemariam, PI): Biomechanical Properties of Blood Cells in Sickle Cell Disease
Study description not available
IRB No. 18-104-1 (Dr. Biree Andemariam, PI): A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study of IMR-687 in Adult Patients with Sickle Cell Anaemia (Homozygous HbSS or Sickle-ß0 Thalassemia)
A Phase 2a, Randomised, Double-Blind, Placebo-Controlled Study of IMR-687 in Adult Patients with Sickle Cell Anaemia (Homozygous HbSS or Sickle-Beta 0 Thalassemia) Background: With a neonatal incidence of 294,000 to 330,000 patients worldwide (Piel 2013), SCA is a rare inherited disorder of red blood cells (RBCs) that is both serious and life threatening. The most common manifestations of SCA include vaso-occlusive crisis, chronic and acute severe pain, acute chest syndrome, stroke, priapism, acute anaemia (particularly from aplastic crisis and splenic sequestration), increased susceptibility to infection, and progressive damage to major organs including the spleen, brain, kidney, heart, lung, skin, retina, vestibular cochlear systems, and bone. In developed countries where there is prenatal Screening and wide spread access to prophylactic and acute interventions, the median age of death remains in the 40s to 50s though many patients succumb to the disease much earlier. Rationale for the study: This is the first study in patients with SCA. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and exploratory pharmacodynamics (PD) and clinical outcomes of IMR-687 in adult patients with SCA. Given that approximately 25% of patients with SCA are currently prescribed HU, it is possible that IMR-687, should it be approved, will be administered as a single agent or co-administered with HU. Therefore, the effects of IMR-687 will be evaluated in patients with SCA who are not receiving HU (Population A) as well as those who are currently receiving a stable dose of HU according to standard of care (Population B). Study design: This is a randomised, double-blind, placebo-controlled study to evaluate the safety, tolerability, PK, and exploratory PD and clinical outcomes of the phosphodiesterase 9 (PDE9) inhibitor, IMR-687. Study population and sample size: 2 populations of patients with SCA: those who are not receiving HU (Population A) and those who are currently receiving a stable dose of HU according to standard of care (Population B). Up to approximately 36 patients will be enrolled in Population A and 18 patients will be enrolled in Population B. Major study interventions: IMR-687 will be supplied as 50, 100 or 200 mg white tablets and will be administered orally with food. Main outcome measures/analyses: Primary Objectives: To assess the safety and tolerability of IMR-687 in adult patients with sickle cell anaemia (SCA), defined as homozygous sickle haemoglobin (HbSS) or sickle-Beta-0 thalassemia, who are not receiving hydroxyurea (HU) and in adult SCA patients who are receiving a stable dose of HU Secondary Objectives: To characterise the pharmacokinetic (PK) profile of IMR-687 in adult patients with SCA who are/are not receiving a stable dose of HU To characterise the PK profile of HU in adult patients with SCA before and after receiving IMR-687 to determine if there is a clinically relevant PK interaction. Exploratory Objectives: To assess the pharmacodynamic (PD) effects of IMR-687 in adult patients with SCA who are/are not receiving stable HU To assess the potential efficacy of IMR-687 on SCA-related clinical outcome measures in adult patients with SCA who are/are not receiving stable HU
IRB No. 18-167-2: Assessment of Cardiac Abnormalities in Sickle Cell Patients Using Echocardiography
Assessment of Cardiac Abnormalities in Sickle Cell Patients Using Echocardiography
IRB No. 18-170-1 (Dr. Sara Tabtabai, PI): Evaluation of a Guideline Directed Medication Titration (GDMT) Program in Patients with Heart Failure with Reduced Ejection Fraction
A patient newly diagnosed with heart failure with reduced ejection fraction requires close follow up for titration of medications as blood pressure, electrolytes and symptoms permit. Although the benefits of guideline directed medical therapy (GDMT) have been well studied, there remains a significant gap in the receipt of GDMT in the ambulatory and hospitalized setting. As such, we seek to assess the utility of focused GDMT clinic to reduce this gap. We hypothesize that implementation of a GDMT focused clinic will reduce the gap, improve medication compliance and in turn, improve the mean ejection fraction, and reduce hospitalization rates.
IRB No. 18-228-2: Assessment of Myocardial Deformation in Adult Patients with Type 2 Diabetes Mellitus
This retrospective case-control study aims to determine if patients with early-stage diabetic cardiomyopathy have subtle myocardial deformation usingspeckletracking echocardiogram. The two aims of the study are (1)to determine whether adult diabetic patients with preserved left ventricular ejection fraction have abnormalities in myocardial deformation and (2) to determine whether adult diabetic patients have impaired diastolic function as assessed by traditional methods as well as by novel method, i.e. left atrial strain, a measurement that has been shown to correlate with pulmonary capillary wedge pressure.
IRB No. 19-036-1 (Dr. Jun Lu, PI): Rheumatology-Dermatology Combined Clinic Patient Registry
The Rheumatology-Dermatology Combined Clinic Patient Registry is a prospective registry that collects patient data within the UConn Department of Dermatology combined clinic for patients being treated for both rheumatologic and dermatologic conditions. Both dermatologists and rheumatologists participate in care for patients suffering from connective tissue disease with both cutaneous and rheumatological manifestations. By establishing combined rheumatology-dermatology clinic, patients will receive collaborative care from both specialties in the same visit. The combined multidisciplinary clinic offers the opportunity for improving care quality, patient satisfaction, and continued education and professional development for physicians. The protocol includes patients over the age of 18 that are being treated in the UConn combined rheumatology-dermatology clinic. This registry will gather data over a 10 year period for future research regarding improving patient care, diagnosis, treatment and long term outcomes for this subspecialty clinic.
IRB No. 19-098-2 (Dr. Lauren Geaney, PI): Range of motion in Achilles tendinitis predicts success with conservative treatment
Dr. Lauren Geaney and Dr. Vinayak Sathe are conducting a research study to better understand which patients are more likely to succeed with physical therapy for the treatment of chronic Achilles tendinitis. The study is titled, "Range of motion in Achilles tendinitis predicts success with conservative treatment." The investigators believe that patients with good initial ankle range of motion do not have the same success with physical therapy as patients with poor range of motion. Therefore, it is also believed that this association may predict which patients may go on to require surgery. Participation in this study involves completing a few short surveys during three to four regularly scheduled clinic visits before and after physical therapy. These surveys focus on general health and well-being, foot function and pain. Some study data will also be collected from the medical record. There will be no changes in the treatment plan or recommendations for patients who participate in this study.
IRB No. 19-105-1 (Dr. Sara Tabtabai, PI): Guideline Directed Medication Titration Program in Patients with Heart Failure with reduced Ejection Fraction
A patient newly diagnosed with heart failure with reduced ejection fraction requires close follow up for titration of medications as blood pressure, electrolytes and symptoms permit. Although the benefits of guideline directed medical therapy (GDMT) have been well studied, there remains a significant gap in the receipt of GDMT in the ambulatory and hospitalized setting. As such, we seek to assess the utility of focused GDMT clinic to reduce this gap. We hypothesize that implementation of a GDMT focused clinic will reduce the gap, improve medication compliance and in turn, improve the mean ejection fraction, and reduce hospitalization rates.
IRB No. 18X-148-2: Sleep Apnea and Diastolic Dysfunction (SADD) Study
Obstructive sleep apnea (OSA) is strongly associated with a number of cardiovascular diseases including hypertension, atrial fibrillation, coronary artery disease, and heart failure. Hypothesis: Obstructive sleep apnea is linked to diastolic heart failure as evident by echocardiographic evidence of diastolic dysfunction. Aims of this study are (1) to determine whether OSA is associated with diastolic dysfunction by comparing the echocardiographic parameters between the subjects with abnormal sleep study and those with normal sleep study;(2) to determine if the severity of OSA as evaulated by the sleep study is associated with the degree of diastolic dysfunction; (3) to determine whether left atrial strain imaging as a part of diastolic dysfunction parameters closely correlates to the severity of OSA.
IRB No. 19-205-2: Vaccination Efficacy with Metformin in Older Adults: A Pilot Study (VEME)
VEME is a double-blinded placebo-controlled trial in men and women over the age of 65 years. It will determine whether metformin can increase influenza (flu) vaccine efficacy in older adults, specifically focusing on cell-mediated responses. Participants will be randomly assigned to either metformin or placebo treatment for a total of 22 weeks. Participants will be vaccinated with high-dose flu vaccine after 12 weeks of treatment. Blood will be drawn prior to treatment, prior to vaccination (week -12 and week -5), and 1, 5, and 10 weeks post vaccination. Peripheral blood mononuclear cells (PBMCs) will be analyzed for cell-mediated responses and serum will be used for flu antibody titers. The overall hypothesis is that metformin will enhance flu vaccine efficacy via targeting age-related changes in intracellular metabolism of immune cells. Primary Outcome: The primary outcome is cell-mediated immune responses to flu vaccine, specifically inducible Granzyme B (GrB) and interferon-? (IFN-?)/interleukin-10(IL-10) ratio in PBMCs stimulated with live flu virus. Secondary Outcomes: Secondary outcomes include flu antibody titers, frailty phenotype, and T cell metabolic cellular profiles. Population: Forty older adults (65 years and older), with approximately 50% men and 50% women. VEME will exclude persons with prediabetes, diabetes, and contraindications to receiving metformin or the flu vaccine. Study Agent: Metformin Hydrochloride Extended-Release, 1500mg/day (three 500mg ER tablets once a day, starting at 500mg ER/day and progressed per current recommendations) and high dose quadrivalent inactivated influenza vaccine (Sanofi Pasteur Inc) Participant Duration: 22 weeks of treatment (up to 27 weeks of participation from screening visit) Study Duration: Recruitment and screening will take place approximately May to July. First dosing of first patient will begin approximately July 15th at the earliest and the first dosing of the last patient will be approximately September 4th at the latest (flu vaccination after 12 weeks of treatment, between October and November). The last patient last visit will be approximately February 10th at the latest (10 weeks post flu vaccine with + 1 week flexibility range).
IRB No. 19-214-1 (Dr. David Steffens, PI): Apathy and Reward Systems in Alzheimer's Disease
Apathy is a common feature of Alzheimer's disease (AD) that is related to functional decline, but its underlying neurobiology is poorly understood. In this application, we propose to use functional magnetic imaging and tasks that focus on the brain's reward system to examine apathy in AD and in late-life depression. Our aim is to identify new targets for intervention to improve apathy in patients with AD.
IRB No. 19-206S-1 (Dr. Cato Laurencin, PI): Just Us Moving Program in the State of Connecticut (JUMP-CT)
JUMP-CT aims to increase light physical activity and reduce weight in the African and Hispanic American populations with type 2 diabetes in the greater Hartford region. This program is a simple behavioral modification program focused on decreasing the hemoglobin A1c levels, a marker of blood sugar levels,in diabetics and in turn improving the management of diabetes and its associated complications and risk factors over time.
IRB No. 13-061C-6.2 (Dr. Biree Andemariam, PI): CASIRE Sickle Cell Renal Disease Cohort International Study Protocol
Study design: This study's design is cross-sectional. Our cross-sectional study approach will allow us to determine particular age cohorts (young children, adolescents and young adults) that might be at risk for developing early renal dysfunction. Further, it will also allow us to determine which estimates of GFR have the best correlation to the changes in renal function. Specifically, we will determine if estimates in GFR, increasing microalbuminuria, or blood pressure changes will be predictive of early renal dysfunction. Study procedures: The research staff, which includes study coordinators from UCHC and CCMC, co-investigators from CCMC, and a principal investigator from UCHC, will only enroll subjects with sickle cell disease who are at steady state and have not had an infection, pain crisis, emergency room visit or hospitalization within two weeks of the time that they are enrolled in the study. Subjects will be screened by the PI or co-investigators, with whom they have a treating relationship. Potential subjects will be told about the study by the PI or co-investigators during a routine clinical visit. Those potential subjects who verbalize interest in learning more about the study will then have an opportunity to discuss the study further with a member of the research staff. If the subject then verbalizes desire to participate, informed consent will be obtained. The questionnaire will then be administered in its entirety by a member of the research staff by verbally asking the subject to answer each question. If there is any uncertainty about the answer to a particular question, the medical chart will be reviewed for verification. We estimate it will take about 20-30 minutes for the subjects to fill out the questionnaire with a research staff member. The subject's involvement ends once the questionnaire is completed.
IRB No. 14-056SF-6.1 (Dr. Pamela Taxel, PI): Investigation of the Ability of the UCONNS (University of Connecticut OsteoNecrosis Numerical Scale) to Predict the Risk for the Developing Osteonecrosis of the Jaw in Patients Receiving Bone-Modifying Therapies for Cancer
The purpose of this proposal is to investigate the risk factors for osteonecrosis of the jaw (ONJ), a known complication of several bone-modifying therapies used in the treatment of advanced cancers. When this complication occurs, it can lead to the discontinuation of important therapy that often impacts the quality of life in skeletal-related events in this population. With the use of a weighted scale that we have devised, the University of Connecticut OsteoNecrosis Numerical Scale (UCONNS), based on known risk factors for ONJ, we aim to validate this scale as a potential predictor of patients at risk, so they may be appropriately monitored and preventative treatment can be initiated. As the medical community has limited guidelines regarding ONJ, we anticipate that this scale, if validated, will foster better communication among providers, as well as improve patient outcomes. This proposal represents a unique collaboration between two investigators in the dental and medical schools at the University of Connecticut Health Center. We hypothesize that the UCONNS can aid in the identification of cancer patients who may be at increased risk for the development of ONJ associated with the use of bisphosphonates and the newer bone modifying therapy, denosumab.
IRB No. 14-057SF-6.1 (Dr. Pamela Taxel, PI): Investigation of the Ability of the UCONNS (University of Connecticut OsteoNecrosis Numerical Scale) to Predict the Risk for the Developing Osteonecrosis of the Jaw in Women Receiving Bone-Modifying Therapies for Breast Cancer
The aim of this proprosal is to investigate the risk factors for Osteonecrosis of the Jaws (ONJ), a known complication of several bone-modifying therapies including bisphosphonates and denosumab, a human monoclonal antibody. ONJ is most commonly seen with the use of these medications in the treatment of skeletal related events in cancer patients with metastatic bone disease, and less frequently seen in the treatment of osteoporosis. This complication often causes significant effects on quality of life that may lead to the discontinuation of important disease-modifying therapy. We have recently developed the UCONNS (University of Connecticut OsteoNecrosis Scale) a weighted scale based on known medical and dental risk factors for ONJ that we are currently validating both retrospectively and prospectively for use as a potential predictor of patients at risk, so they may be appropriately monitored and preventative treatment can be initiated. The current proposal aims to add to the UCONNS by prospectively measuring serum bone markers that may prove valuable in predicting patients that are at increased risk for developing ONJ. We will follow patients who are being treated with bone modifying agents in order to prospectively measure and evaluate a panel of unique parameters of bone metabolism to identify potentially predictive serum biomarkers for the development of ONJ. We hypothesize that the UCONNS can aid in the identification of breast cancer patients who may be at increased risk for the development of ONJ associated with the use of bisphosphonates and the newer bone modifying therapy, denosumab.
IRB No. 14-107CS-6.2 (Dr. Biree Andemariam, PI): Identification of Patient-specific RBC-endothelial Cell Adhesion Profiles as Markers of Sickle Cell Disease Severity.
The research objective of this proposal is to determine in 25 adult/pediatric SCD patients (1) the relationship between pain severity phenotype and the strength of adhesion between single red blood cells (RBCs) and single endothelial cells (ECs) isolated from peripheral blood and (2) the ex vivo effect of pharmacologic inhibitors on RBC-EC adhesion, creating both a patient-specific adhesion profile and therapeutic signature. The results are expected to lead to novel individually-targeted approaches to inhibit the onset and limit the duration of painful vaso-occlusive episodes (VOEs). Our central hypothesis is that the strength of adhesion between RBCs and ECs at baseline is related to patient-specific pain severity phenotype, resulting in the need for patient-specific drug therapy. To test the hypothesis, we will pursue the following three specific aims: Investigate the relationship between pain severity phenotype and baseline RBC-EC adhesion profile in SCD subjects -- We will measure the strength of adhesion between single RBCs-ECs from SCD subjects at baseline. Baseline/steady-state adhesion profiles will be compared on an inter-patient level to determine which adhesion profiles correlate most highly with pain severity phenotype. Assess the association of VOE severity with changes in RBC-EC adhesion from baseline to VOE onset. We will measure the change in strength of adhesion between single RBCs-ECs from baseline to VOE onset. Changes in adhesion will be compared on an inter-patient level to determine whether relative changes in adhesion profile at VOE onset correlate with VOE severity. Test the ex vivo effect of targeted pharmacotherapy on the RBC-EC adhesion profile of SCD subjects -- We will measure (at baseline and at VOE onset) the ex vivo inhibitory effect of two known RBC-EC adhesion blockers (propranolol and abciximab) to identify patient-specific anti-adhesive therapeutic signatures.
IRB No. 14-136CS-6.2 (Dr. Biree Andemariam, PI): Hemoglobinopathies and Bone Health
This research study has two purposes. The first purpose is to determine whether having sickle cell trait is a risk factor for the development of bone thinning at an earlier age than expected. Nearly 10% of African Americans carry sickle cell trait and most of them are unaware of it. African Americans are less likely to develop thin bones than whites, but if they sustain a bone fracture, they are more likely to die from it. We believe having sickle cell trait may lead to bone thinning and predispose a subset of African Americans to dangerously thin bones. The second purpose is to try to understand why individuals with sickle cell disease have thinner bones than healthy individuals do. Doctors have already discovered that people with sickle cell disease have very thin bones, but they have not determined why. Our study will try to identify whether the bone thinning is from the body not making enough bone or from the body losing bone once it is made.
IRB No. 17-193C-6.2 (Dr. Biree Andemariam, PI): Measures of Functional Ability in Adults with Sickle Cell Disease
This study is a prospective, clinical/translational research pilot study using a web-based, daily survey. Pain in adults with sickle cell disease (SCD) is unique in that patients often experience acute and chronic pain simultaneously. Numerical rating scales are often unhelpful in the measurement of this type of pain as patients tend to report high pain scores despite noted variations in functional ability. This pattern of functional improvement with continued report of high pain intensity scores is common in patients with recurrent and chronic pain. A functional assessment tool that can reflect functional changes over brief time periods (days) is necessary to 1) allow for the examination of the impact of acute pain on usual function, 2) investigate the extent to which acute pain symptoms create a burden for patients and caretakers, 3) use as an outcome measure that would allow for objective measurement of changes in functioning as the result of acute pain interventions, and 4) study individual differences in functioning within specific patient groups. We have previously developed the YAPFAQ, a measure of acute functional ability in youth with sickle cell disease. No tool for measurement of daily functional ability in adults with SCD exists. The aim of this project is to provide preliminary data on item content for an adult acute functional ability tool, while examining the impact of other variables such as pain, mood and sleep on daily function in individuals with SCD. We propose to complete a pilot study of 40 adults between the ages of 21-40 years with SCD. Each adult will access an online survey daily for 30 days to report 20-30 items regarding their functional ability, sleep, mood and pain. Participants will access the daily survey through any standard web-browser using REDCap and complete the survey between 6pm-10pm each day.
IRB No. 18-036S-6.2 (Dr. Biree Andemariam, PI): Development of Novel Tools to Treat Vaso-Occlusive Pain in Sickle Cell Disease
This study is a prospective, clinical/translational research study with both long term and immediate goals. The long-term goals of this project are two-fold: (i) to quantitatively understand how the adhesive cellular interaction between blood cells and the endothelium can be modified to prevent VOE; (ii) To create simple point-of-care diagnostic tests that will indicate the risk of VOE onset. Our central hypothesis is that the onset of VOE is temporally-related to an increase in blood adhesion and viscosity that can be reversed with anti-adhesion therapy. The immediate goals of this project are to (1) measure the relationship between steady-state SS-RBC--endothelium adhesion and VOE frequency, and identify changes in SS-RBC--endothelium adhesion during VOE onset, (2) demonstrate an ex vivo effect of anti-adhesive therapy on SS-RBC--endothelium adhesion that directly or indirectly targets the cAMP-PKA pathway, and (3) develop simple a single-use microfluidics device capable of indicating the risk for VOE. Atomic force microscope (AFM) and microfluidics will be used to measure adhesion of endothelial proteins to human SS-RBCs isolated from SCD patients at steady-state (no VOE) and at VOE onset. AFM allows specific quantification at the single molecule level of both the number and strength of protein-protein binding events on the RBC surface. Microfluidics allow for high throughput screening. To achieve our goals, we will complete the following specific aims: Aim 1: Determine the relationship between (1) steady-state SS-RBC adhesion and frequency of VOEs and (2) changes in SS-RBC adhesion level and onset of VOEs. Aim 2: Measure the ex vivo effect of pharmacologic blockade of receptor--ligand adhesion in the B-adrenergic system. Aim 3: Design, fabricate, and validate a simple, inexpensive, single-use microfluidics device coupled with a smart-phone kit and software application that will indicate the risk for VOE onset. Our expected outcomes and accomplishments are to (1) identify a relationship between enhanced SS-RBC adhesion and VOE onset, (2) identify therapies capable of limiting the onset and duration of VOEs and (3) create a single-use microfluidics device capable of indicating the risk of VOE onset. This has the potential to impact the development of needed treatments to prevent and reverse VOEs in millions of individuals with SCD worldwide. We will enroll 5 eligible subjects with SCD and 5 healthy controls over a three-year period. During this time, each SCD subject will donate 5 baseline blood samples to ensure we establish a true baseline. Baseline blood samples will be collected periodically during routine clinic visits over the three year study enrollment; at this time, subjects will donate 12 cc of blood. SCD subjects will also document when a painful vaso-occlusive episode (VOE) occurs and will donate a total of 3-4 VOE blood samples over the three year study period. During each VOE blood draw, SCD subjects will donate 12cc of blood. The initial VOE blood sample must be obtained within 48 hours of the VOE onset. Subsequent samples can be obtained in the days following VOE onset or at the time of a new VOE episode. Healthy controls will donate 12 cc of blood on three occasions, with each blood draw being at least one month apart. Blood will be analyzed for CBC/differential, hemoglobin electrophoresis, epinephrine levels, RBC adhesion, and blood viscosity. With this approach, we will test the hypothesis that there is a relationship between steady-state SS-RBC adhesion and frequency of VOEs (Specific Aim #1). SS-RBC adhesion at VOE onset will be compared to steady-state in order to test the hypothesis that enhanced SS-RBC adhesion mediates VOE (Specific Aim #1). Utilizing blood collected from subjects with SCD during steady-state and within 48 hours of VOE onset, we will measure the adhesion of SS-RBCs to the endothelial ligands.
IRB No. 14-221-3.2 (Dr. Martin Freilich, PI): Two-implant supported maxillary overdentures: Clinical and patient reported outcomes.
PROJECT SUMMARY Maxillary overdentures supported by four implants have clearly shown to be effective and provide improved function as compared to conventional dentures, particularly when alveolar ridges are resorbed and when palate form is shallow. This preliminary, descriptive study aims to prospectively study the efficacy of only 2 implants to support maxillary complete dentures. The specific aims of this study are: 1) To generate an estimate of three-year implant and prosthesis success for two implant-retained maxillary complete denture prostheses; and 2) To better understand patient reported outcomes across time. Upon IRB approval and patient recruitment into the trial using pre-determined inclusion and exclusion criteria, 20 maxillary edentulous patients will be provided with two implants to support their existing denture. Each patient will receive two dental implants bilaterallly in the maxillary anterior region at the lateral incisor/canine regions. After successful osseointegration, two "Locator" abutments will be inserted over the implants and the patient's existing denture will be attached to the abutments through a laboratory reline of the denture and thus converted to a two-implant retained maxillary overdenture. Thereafter follow-up exams will be performed and clinical outcomes and patient-reported outcomes will be studied at baseline (conventional complete dentures); 1 week post-insertion of relined maxillary overdenture; 6-months; 1 year post-insertion; 2 years post-insertion; and 3 years post-insertion (all two-implant supported maxillary overdenture). The clinical outcomes will be recorded in a descriptive manner for variables including implant survival, surgical complications, radiographic bone levels, plaque index/bleeding index around the implants, prosthetic complication, wear or loosening of the abutments, replacement of the nylon inserts and other descriptive variables. The patient-reported outcomes will be recorded at follow-up appointments using a visual analog scale (VAS) and a modified oral health impact profile (OHIP-14). Additional follow-ups as required by each patient for any adverse outcomes related to treatment will also be documented. Those variables that allow comparison to conventional denture will be compared using statistical measures. SPECIFIC AIMS This descriptive, patient based study is designed to determine implant survival for dental implants and the success of implant retained complete removable prostheses when only two implants are utilized. It is well known that there is a projected increase in the number of edentulous patients in the United States. It is also known that maxillary edentulism is more common than mandibular edentulism. While the general standard of care for complete tooth replacement in the maxillary arch is the "conventional" complete denture, it is well established that maxillary implant overdenture supported by four implants generally outperforms the conventional denture. The objective of this study is to determine whether placement of a minimal number (2) of implants supporting a maxillary overdenture can result in good implant / prosthesis survival and satisfactory patient satisfaction and quality of life. Positive results from this pilot study can be used to generate hypotheses supporting a larger clinical study that may have an impact in re-defining the minimal intervention necessary for rehabilitation of the edentulous maxilla. We plan to accomplish our objectives by the pursuing the following two specific aims: To generate an estimate of three-year implant and prosthesis success for two-implant retained maxillary complete denture prostheses. The clinical outcomes will be recorded in a descriptive manner for variables including implant survival, surgical complications, radiographic bone levels, plaque index/bleeding index around the implant.
IRB No. 18-050-1 (Dr. Jun Lu, PI): Corrona Psoriasis Registry
The Corrona Psoriasis Registry is a prospective, multicenter, observational registry that will compare the safety of approved psoriasis therapies in patients across the nation who are actively being treated with these medications by dermatologists. Patients must have been started on, or have been switched to a biologic psoriasis medication within the 12 months preceeding enrollment. Adverse events of special interest, including malignancy, will be followed for all patients.
IRB No. O19-030-2 (Dr. Robert Arciero, PI): The STaR Trial - Surgical Timing and Rehabilitation for Multiple Ligament Knee Injuries: A Multicenter Integrated Clinical Trial
The purpose of the STaR Trial is to look at the best way to treat people with a multiple ligament knee injury. A multiple ligament knee injury is an injury in which two or more of the major ligaments in the knee are completely torn. This study is looking at when is the best time to do surgery and when is the best time to start rehabilitation after surgery. More specifically, it is interested in determining the effects of early versus delayed surgery and early versus delayed post-operative rehabilitation for the treatment of multiple ligament knee injuries on return to pre-injury activity. This study will determine how the timing of surgery and rehabilitation affect when someone with a multiple ligament knee injury is able to return to their pre-injury level of activity, whether it’s for work or sports activity. Researchers will follow participants' recovery and return to activity for 24 months. During this time, researchers will record information from participants' routine clinical visits and send questionnaires to participants' to track their progress and return to activity that can be completed on a smartphone or computer.
IRB No. 19-121JS-1: Ellagic Acid, Urolithins and Colonic Microbial Communities Affected by Walnut Consumption
The purpose of this study is to investigate whether adding walnuts to your diet can have a beneficial effect on your colon. Walnuts contain a natural compound called ellagitannin that is broken down in the stomach to ellagic acid. Ellagic acid is further broken down by your gut microbiota into a group of polyphenolic compounds called urolithins that have powerful anti-inflammatory actions. The gut microbiota is defined as the community of bacteria, fungi, viruses, etc. that live in your gut. Increasing evidence suggests that polyphenol consumption is associated with lower risk of colorectal cancer. We aim to investigate how a person's gut microbiome may contribute to your ability to form these powerful antioxidant urolithin compounds. Antioxidants are a group of substances that have the ability to reduce inflammation. In this study, we will collect demographic information and dietary records, and perform tests on proteins, DNA and/or RNA from samples of colon biopsies, blood, stool and urine to investigate how a person's microbiome may contribute to their ability to form urolithins.
IRB No. 17-072-6.2 (Dr. Damion Grasso, PI): Adaptation and Resilience in Childhood Study (ARCS) Pilot
In the current application we propose applying advances in developmental measurement science, including those developed in our own lab, towards sensitive characterization of DV 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 experiencing an acute stage of DV exposure in which mother and child are receiving services at a DV shelter. 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 and autonomic (heart rate, skin conductance) responses to laboratory-based threat stimuli, and (5) observed and reported maternal sensitivity and parent-child interaction. We also will apply a semi-structured, timeline follow-back approach in the mother interviews, which we have developed, to assess and characterize children’s peritraumatic responses (i.e., during and/or immediately after the exposure) to DV, which our preliminary data suggests may be predictive of PTS symptoms. In the current project, families will be recruited from nearby DV shelters. Research visits will occur at our newly established early child development laboratory on the UConn Kane Street property in West Hartford and will last approximately four hours. Families will be compensated for their time. Specific Aims: Aim 1. To employ a multi-method assessment approach towards examining links between DV exposure, peritraumatic behavioral responses, and PTS symptoms in shelter-residing preschool age children recently exposed to DV. Aim 2. To examine associations between multiple indices of behavioral and physiological threat detection and reactivity (i.e., attention bias to threat, observed fear/anxiety, and autonomic reactivity) and trauma-related symptoms. Aim 3. To identify factors in the caregiving environment that appear to buffer or potentiate trauma-related symptoms and associated patterns of threat detection and reactivity.
IRB No. 19-148-2 (Dr. Biree Andemariam, PI): An Open-label Extension Study of IMR-687 in Adult Patients with Sickle Cell Anemia (Homozygous HbSS or Sickle-ß0 Thalassemia) Who Participated in Study IMR-SCD-102
Study Title:An Open-label Extension Study of IMR-687 in Adult Patients with Sickle Cell Anemia (Homozygous HbSS or Sickle-B0 Thalassemia) Who Participated in Study IMR-SCD-102 Background: With a neonatal incidence of 294,000 to 330,000 patients worldwide (Piel 2013), SCA is a rare inherited disorder of red blood cells (RBCs) that is both serious and life threatening. The most common manifestations of SCA include vaso-occlusive crisis, chronic and acute severe pain, acute chest syndrome, stroke, priapism, acute anemia (particularly from aplastic crisis and splenic sequestration), increased susceptibility to infection, and progressive damage to major organs including the spleen, brain, kidney, heart, lung, skin, retina, vestibular cochlear systems, and bone. In developed countries where there is prenatal Screening and wide spread access to prophylactic and acute interventions, the median age of death remains in the 40s to 50s though many patients succumb to the disease much earlier (Platt 1994; Lanzkron 2013; Paulukonis 2016). Rationale for the study:Study IMR-SCD-102-EXT is an extension of Study IMR-SCD-102. During the extension, IMR687 100 mg will be administered orally once daily. Since Study IMR-SCD-102 is the first study in patients with SCA, an extension will provide long-term safety and tolerability data for these subjects. In addition, long-term pharamcodynamic (PD) and efficacy data will be collected. Study design: Patients are eligible for this open-label extension study immediately following the End-of-Study visit for Study IMR-SCD-102 (i.e., approximately 30 days after the last dose of study drug in the Phase 2a study). Following screening assessments to determine continued eligibility, patients will be enrolled into this extension study. IMR687 100 mg will be administered orally once daily. Patients will return to the study site for visits at week 1, and months 1, 4, 8, and 12 during the first year. Thereafter, patients will return to the study site every 6 months during years 2, 3, and 4. Telephone-based check-ins may be performed on weeks where there are no scheduled assessments or in the event of lack of patient availability for an in-person visit. Safety and concomitant medications will be monitored throughout the study; PD and clinical outcome measures will be performed at selected site visits. Study sample size:Approximately 70 patients currently participating in Study IMR-SCD-102 are expected to be eligible for this long-term extension. Major study intervention:The dose of IMR-687 to be administered in this extensions study is 100 mg per day as a single oral dose. This is the optimum dose expected being tested in the Phase 2a study and is considered to have positive pharmacodynamic effect, based on preclinical modelling and exposures in the FIH study of IMR-687 in healthy volunteers.Pending emerging data from Study IMR-SCD-102, the dose of IMR-687 may be adjusted in this study as appropriate. Main outcome measures/analyses: Primary objectives: To assess the long-term safety and tolerability of IMR-687 in adult patients with sickle cell anemia (SCA), defined as homozygous sickle hemoglobin (HbSS) or sickle-B0 thalassemia, who were previously enrolled in Study IMR-SCD-102. Exploratory objectives: To assess the pharmacodynamic (PD) effects of IMR-687 in adult patients with SCA who were previously enrolled in Study IMR-SCD-102. To assess the potential efficacy of IMR-687 on SCA-related clinical outcome measures in adult patients with SCA who were previously enrolled in Study IMR-SCD-102.
IRB No. 20-084-2 (Dr. Zhichao Fan, PI): Mechanisms and Roles of Integrin Activation of Human Blood Leukocytes
Background, Rationale and Significance: Integrins are key mediators of the recruitment of leukocytes which play critical roles in human immunity and inflammatory diseases. Insights about Integrin function hold out the prospect improved inflammatory disease prevention. Blood leukocytes including neutrophils, monocytes, and lymphocytes, all have a recruitment cascade during inflammation and infections. They can first roll on the vascular endothelium, firmly adhere (arrest) on the vascular endothelium, spread on the vascular endothelium, perform intravascular crawling, transmigrate through vascular endothelium, and finally, migrate to the site of inflammation or infections. This cascade is essential for the recruitment and immunological function of leukocytes and involved in many infectious and inflammatory diseases. Integrins, are a group of adhesion molecules vital for the recruitment cascade. Studying the mechanisms and roles of integrin activation will bring new insights into leukocyte recruitment and immune functions and invite discovery of novel treatments for infectious and inflammatory diseases. (See Protocol-Appendix for Leukocyte Recruitment, Integrin Activation Pathways and Super Resolution/ Flow Imaging Graphics- pg.10-16) This protocol is used to develop a continuing supply of fresh blood donations for the Integrin Research Laboratories under the direction of the PI @ UConn Health, Dept of Immunology where the PI recently joined. 2 recent PI authored publications are included for reviewer, explanatory of the Integrin research for which materials are to be utilized in ongoing experiments.
IRB No. 10-273S-2 (Dr. Robert Clark, PI): The Role of Unique Lipids Derived From Common Human Bacteria in Multiple Sclerosis
Study description not available
IRB No. 14-193CH-6.2 (Dr. Damion Grasso, PI): Prenatal Exposure to Stress
The purpose of the repository is to build a research program focused on epigenetic influences of early childhood exposure to violence and disruption in the development of the stress response system. The work will continue the focus on the glucocorticoid receptor gene FKBP5 and it's companion molecules in the stress response pathway.
IRB No. 18-038-1 (Dr. Damion Grasso, PI): Intergenerational Transmission of Trauma-Related Risk
Evidence suggests that the effects of trauma exposure, including posttraumatic stress disorder (PTSD), can be transmitted across generations to shape pathways to psychological impairment in offspring; however, the mechanisms and timing of these effects are not well known. The purpose of this study is to better understand these mechanisms. It builds on an ongoing study to examine associations between maternal PTSD during pregnancy, newborn infant epigenetic patterns, and infant stress reactivity at 6 months of age, in the context of the caregiving environment. Hispanic/Latino participants who had enrolled in the ongoing study and who have agreed to be contacted and invited to participate in future research opportunities will be invited to participate. Specific aims are to examine (1) associations between maternal PTSD and epigenetic patterns in both mothers and newborn infants, (2) links between maternal PTSD during pregnancy, maternal and newborn epigenetic patterns, and biological and behavioral indicators of stress reactivity in 6-month-old infant offspring, and (3) whether aspects of the caregiving environment moderate the effects of maternal PTSD and epigenetic patterns on infant stress reactivity.
IRB No. 20-122-1 (Dr. Lihong Wang, PI): A Neural Study of the Maturational Shift in Emotion Regulation in Healthy Aging and Depression
This study will focus on examining the impacts of age and depression history on emotion regulation, both behaviorally and neurally. Maladaptive emotion regulation in older subjects with a history of depression is a risk for depression relapse. Confirming the failure in the normal adult maturational shift in emotion regulation in remitted depressed patients and identifying neural mechanisms supporting emotion regulation strategies used in remitted depressed subjects will inform the future development of novel prevention or treatment interventions.
IRB No. 20-137-1 (Dr. Sejal Thacker, PI): A PILOT RCT STUDY COMPARING DIMENSIONAL ALTERATIONS AFTER SOCKET GRAFTING WITH XENOGRAFT VERSUS ALLOGRAFT
6.1 MASTER LAY SUMMARY STUDY TITLE - A Pilot RCT Study comparing dimensional alterations after socket grafting with xenograft versus allograft BACKGROUND - After extraction of a tooth the healing socket goes through a remodeling process in which there is a substantial dimensional loss of bone volume. Various bone graft materials have been used to minimize this bone volume loss and facilitate future dental implant placement. This study is to test the differences between two bone grafting materials - a xenograft and an allograft. Both grafting materials are extensively and routinely used and are considered standard of care. AIM - The aim of the study is to compare the xenograft and allograft biomaterial when used in extraction sockets to minimize dimensional changes. The comparison between the two materials will be done using a 3-dimensional scan and by doing intraoperative measurements. The performance of the graft will also be compared from a histological standpoint. HYPOTHESIS - The null hypothesis is there is no difference in the performance of the two biomaterials with respect to dimensional changes after 6 months of healing. PRIMARY OBJECTIVE - Horizontal and vertical dimensional changes of extraction sockets as evaluated in a 3 dimensional radiograph (CBCT scan) pre-extraction and 6 months post extraction when grafted with xenograft versus allograft. SECONDARY OBJECTIVE - Horizontal and vertical dimensional changes of extraction sockets as evaluated intraoperatively in patients mouth pre-extraction and 6 months post extraction when grafted with xenograft versus allograft. Histological difference in the healing of the graft particles. A biopsy of the site will be done at 6 months and the core will be used for histological analysis Amount of newly regenerated bone will be evaluated using a micro CT analysis. The biopsy cores used for histology will be used for this purpose as well.
IRB No. 20-123-1 (Dr. David FitzGerald, PI): Child Clinic Registry
The objective of this project is to develop a data registry. A registry collects, processes, stores and distributes data for future scientific investigation. The registry will consist of medical record information obtained from patients treated at Child and Adolescent Psychiatry Outpatient Clinic at UConn Health. The treatment in this clinic is focused on addressing psychological and psychiatric behaviors.
IRB No. 20-186-1 (Dr. Biree Andemariam, PI): SARS-CoV-2 Serosurveillance in Health Care Workers on COVID-19 patients
Infection with SARS-CoV-2 causes human COVID-19 (HCoV-19). Health care workers are at risk of being exposed to this virus. Since majority of COVID19 patients have been asymptomatic or mildly symptomatic, it is important to identify those who have been exposed, converted to sero-positivity and acquired potential immunity. Finding of seroconversion among healthcare workers will help understand the epidemiology of this infection in the healthcare setting and potentially better inform the workers and their associates
IRB No. 21-001-1 (Dr. Daniel Rosenberg, PI): Determining the Role of Peanut Consumption on Dietary Habits, Gut Microbiome, and Colon Biomarkers in a Healthy Population
Colorectal cancer (CRC) is the second cancer-related cause of death among men and women in the United States. Dietary lifestyle is a contributing factor to CRC risk, and it plays a role in changing the bacteria living in the gut. Current research are now focusing on studying the effects of these bacteria and the compounds they produce, and how it is affecting cancer progression. Peanuts are part of the American diet, a food that is rich in nutrients such as protein, fiber, healthy fats, bioactive compounds, vitamins and minerals. The objective of this study is to determine if increasing peanut intake influences other dietary habits and gut bacteria composition. Secondary aims are as follows: 1) to understand if changes in dietary habits and gut bacteria affect biomarkers in the colon, and 2) to study possible mechanisms in early CRC prevention. Therefore, a dietary intervention will test the effects of peanut intake on dietary habits, gut microbiota, and colon biomarkers. Healthy participants (50-65 years old) scheduled for a screening colonoscopy will be recruited and start a 1-week washout period where they will be asked to avoid peanuts/nuts and other foods provided in a list throughout the study period. Then, they will be randomized into peanut or control group, where control gorup is gender and body mass index matched to peanut group. For 3 weeks, the peanut group will be consuming 2 ounces of roasted peanuts daily, while the control group will not consume peanuts. At baseline and end of clinical trial, blood, stool and 3-day dietary records will be collected. After the intervention, participants will have the colonoscopy done and eight colon biopsy samples will be collected. The hypothesis is that peanut consumption will increase intake of other healthy foods (increase in dietary fiber) and change the bacteria in the gut to a more diverse and rich community when compared to baseline and matched controls. We also expect an increase anti-inflammatory colon biomarker since peanuts contain fiber, unsaturated fats, and antioxidants that may help prevent cancer.
IRB No. 21-025-2 (Dr. Damion Grasso, PI): Impact of Perinatal Pandemic-Related Stress on the Early Caregiving Environment
The purpose of this online survey study is to learn about how the COVID-19 pandemic has impacted the experiences of Connecticut residing individuals during pregnancy and as a new parent. Survey questions assess sociodemographic characateristics, positive and stress personal and family experiences, mental health and well-being, information about pregnancy, birth, and the caregiving environment, and information about infants. The survey will serve as the foundation for a larger study being proposed, which is currently under review by the National Institute for Child Health and Development (NICHD) for possible funding. Data from the survey will be used for preliminary data in support of this larger study, as well as to contact interested individuals for possible participation in the larger study. Survey data will be kept from contact information, which will be collected and maintained on a separate Qualtrics survey database. These two surveys will be matched with a unique code that will be generated by the participant.
IRB No. 20-210S-1 (Dr. Nathaniel Rickles, PI): The Feasibility and Effectiveness of an Opioid Package Prototype (OPP) to Impact Opioid Prescribing, Dispensing, and Patient Use Outcomes
This study is looking at how the packaging of opioid medication affects the use of opioids following surgery. The study is comparing opioid use when provided in a standard amber vial (normal orange bottle) versus a blister pack called the Opioid Package Prototype, or “OPP” for short. Study participants will receive their post-surgery opioid medication from Arrow Pharmacy (located in the Outpatient Pavillion) in one of the two packages, which are pre-assigned. Participants will also complete surveys and/or interviews before surgery and at 1 week, 1 month and 3 months after surgery. Basic criteria to participate include being an adult having one of 17 common surgical procedures by a participating orthopaedic surgeon and using opioid medication for post-operative pain.
IRB No. 21-070J-1 (Dr. George Kuchel, PI): Dynamic assessment of immune system in COVID-19 patients: Flu Vaccine Pilot Study 1
This prospective, single-site pilot study is designed to determine the feasibility to recruit and enroll COVID-19 convalescent adults into a study that will assess immunity changes associated with aging. To complete a 12 subject pilot study with the following aims: To establish feasibility of conducting a larger trial with the enrollment of COVID-19 convalescent adults, we will enroll 6 older (65 years and older) and 6 young (25-50 years) adults that have recovered from COVID-19. To gather preliminary data on epigenomic signatures of responsiveness to the seasonal influenza vaccine in adults recovered from COVID-19. To gather preliminary data on microbiome signatures of COVID-19 sequelae. The objective of this project is to systematically identify the most relevant factors that are associated with the prolonged effects of COVID-19 on immunity by applying a systems immunology approach that incorporates high-resolution immunologic assays with state-of-the-art genomic, proteomic, metabolomic assays. Major questions we will address include: i) which immune cell types and gene expression programs are remodeled with COVID-19 in the long term?; ii) do these immune alterations associate with changes in vaccine responsiveness?; iii) do COVID-19 sequelae differ between older and younger adults, and between men and women?; iv) are there multi-omics biomarkers of reduced immunity due to COVID-19? To answer these questions, we will establish a longitudinal cohort of young (25-50 yrs old) and older adults (≥65 yrs) who recovered from COVID-19 and we will characterize their immune systems in detail under baseline and upon influenza vaccination.
IRB No. U20-082-2 (Dr. Jayesh Kamath, PI): A Phase 3, Multicenter, Randomized, Double-blind Trial of Brexpiprazole as Combination Therapy with Sertraline in the Treatment of Adults with Post-traumatic Stress Disorder. Protocol No. 331-201-00071
This clinical research trial will study adults who have experienced or witnessed a traumatic event within the past 9 years and have unwanted symptoms as a consequence of that traumatic event. An investigational drug is being studied with another medication for the treatment of post-traumatic stress disorder (PTSD). Total participation is approximately 4 months. This includes a screening phase, a double-blind treatment phase, and a follow-up phase. All study-related visits, tests, and drugs will be provided at no cost. In addition, reimbursement for study-related travel may be provided.
IRB No. O21-071-2 (Dr. Jayesh Kamath, PI): A Randomized, Double-blind, Multicenter, Placebo-controlled Study to Evaluate the Efficacy, Safety, and Tolerability of Esketamine Nasal Spray, Administered as Monotherapy, in Adult Participants with Treatment-resistant Depression (ESKTRD4005)
This is a clinical research study of an investigational medication for adults with treatment-resistant depression (TRD). The purpose of this study is to evaluate the effectiveness, safety, and tolerability of the investigational medication when it is used alone in adults with TRD. Study participation will last up to 24 weeks and includes a screening phase, a double-blind phase, an open-label/observation phase, and a follow-up phase. Qualified participants may receive investigational study medication and some study-required medical care at no cost.