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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. 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. 06-577-2 (Dr. Augustus Mazzocca, PI): Proximal Humerus and Distal Femur Intramedullary Aspiration During Standard Rotator Cuff or ACL Repair: A Pilot Study.
Use of bone marrow obtained from the pelvis in various orthopedic procedures has been well documented. Less is known regarding bone marrow harvested from the proximal humerus and distal femur. This study has incorporated a method in which bone marrow is harvested at the time of surgery without an increase in surgical procedures. These samples are analyzed in our laboratory to determine if these sites are potential sources of adult stem cells.
IRB No. 07-131-1 (Dr. Jonathan Covault, PI): Behavioral Gene Bank
The purpose of this registry/repository is to collect diagnostic data (psychiatric and medical diagnoses) and tissue specimens from subjects and/or family members in order to build a Behavioral Gene Bank (BGB). The registry/repository aims to study; subjects with known or suspected genetic or medical syndromes; families with high concentrations of psychiatric illness; and subjects with dysmorphic features or other clinical characteristics suggestive of a genetic or chromosomal disorder. Relatives of individuals with these features and healthy controls will also participate. Subjects will be invited to participate in further behavioral studies in the future.
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. 089-89-1 (Dr. Victor Hesselbrock, PI): Participating Center for Genetics for Alcoholism (Collaborative Study) COGA
Study description not available
IRB No. 09-065-1 (Dr. Emil Coman, PI): Church Based Diabetes Prevention and Translation Study-2
The purpose of this study is to test a church-based intervention for the early detection and reduction of risk factors of diabetes mellitus among African Americans. This proposed project is an extension of Dr. Boltri's previous study entitled "Early Identification and Intervention in Persons at High Risk for Diabetes Mellitus Using a Church Based Model." This study will translate the previous NIH-DPP into a community setting, thereby meeting the Healthy People 2010 objective of reducing the disease and economic burden of diabetes.
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. 11-026-1 (Dr. Biree Andemariam, PI): Evaluation of Inflammatory Response to Influenza Vaccination in Sickle Cell Disease.
This study will evaluate the response of humans with sickle cell disease to routine vaccinations, specifically immunization for the influenza virus. It succeeds a pilot/feasibility study that was conducted and confirmed that appropriate specimens could be collected from human subjects with sickle cell disease and healthy controls and that the necessary assays could be run to examine inflammatory markers and components of the immune system present in the blood of subjects. The aim of this study is to utilize blood samples obtained from both individuals with sickle cell disease and healthy volunteers in order to determine whether SCD individuals exist at baseline in a state of heightened inflammation as compared to the healthy volunteers. The study will then evaluate whether sickle cell patients have an enhanced inflammatory response to the influenza vaccine as compared to healthy individuals through an equivocal analysis from a blood draw 4-6 weeks post-vaccination. In summary this study will consist of two separate blood draws, a pre-vaccination blood draw within 4 weeks of influenza vaccine administration and a post-vaccination blood draw within 4-6 weeks after immunization for the influenza vaccine.
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. 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. 13-060-3 (Dr. Bruce Liang, PI): A Novel Biomarker for Diagnosing and Quantifying Skeletal Injury
Study description not available
IRB No. 13-048-6 (Dr. David Steffens, PI): Neurobiology and Acute Treatment Outcomes of Late Life Depression
This study seeks to further the scientific understanding of the complex relationships among depression, neuroticism, persistent depression and cognitive impairment. An aim is to identify older depressed adults who are at risk for negative outcomes by studying older adults, assessing their level of neuroticism and cognitive performance, their response to treatment and their cognitive outcomes over time. This group over time will be compared to a group of non-depressed older adults.
IRB No. 13-056-2 (Dr. Jonathan Covault, PI): Dutasteride Treatment for the Reduction of Heavy Drinking
This study will use a 12-week randomized, placebo controlled clinical design to examine the safety and efficacy of dutasteride treatment (1mg daily) combined with medical management to help reduce or stop drinking among a sample of 160 men with hazardous levels of alcohol use. Other aims are: to examine the durability of effects of dutasteride treatment on drinking and heavy drinking during a six-month post-treatment follow-up; to examine whether treatment response is moderated by a common genetic variation, H5Q, in the neuroactive steroid biosynthetic enzyme 3a-hydroxysteroid dehydrogenase gene AKR1C3 that has been associated with alcohol dependence; and to examine the potential effects of dutasteride on the relations among daily mood and daily events on drinking and heavy drinking, and the potential effects of dutasteride on daily reports of alcohol subjective effects to identify potential intermediate effects of dutasteride on treatment outcomes.
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. 13-014-1 (Dr. Bruce Strober, PI): A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study Comparing the Efficacy and Safety of LY2439821 to Etanercept and Placebo in Patients with Moderate-to-Severe Plaque Psoriasis
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. 14-129-6 (Dr. Biree Andemariam, PI): Sickle Cell Trait-related Blood Cell Adhesion as a Determinant of Disparate Cancer Treatment Outcomes
SPECIFIC AIMS The research objective of this proposal is to determine if blood cells from persons who are sickle cell trait carriers react adversely to standard chemotherapy compared to blood cells from persons without this genotype. African-American women have disparate breast cancer survival rates compared to white women that cannot be fully explained by either socio-economic or tumor marker expression differences. While sickle cell trait (SCT) is rare in the white population, nearly 10% of African-Americans carry SCT and most are unaware. Several case reports in the literature have described adverse reactions to systemically administered chemotherapy in African-Americans with SCT raising the possibility that chemotherapy-induced intravascular sickling may occur. Subsequent vaso-occlusion (overt or sub-clinical) may give rise to symptoms such as pain and nausea, or clinical signs such as unexplained anemia and renal insufficiency. These signs and symptoms may lead to treatment delays, dose-reductions and in some cases, cessation of therapy altogether--- all of which can impact efficacy and, most importantly, survival. We have previously shown that red blood cells (RBCs) from individuals with SCT are more adhesive to vascular endothelium than normal RBCs and that this adhesion is enhanced under physiologic stress conditions. We aim to compare the effect of chemotherapy on RBC adhesion to endothelial proteins in white women and in African-American women with and without SCT. The results are expected to lead to novel approaches to reverse disparities in cancer treatment outcomes among African-Americans. Our central hypothesis is that RBCs from African-American women with SCT are more adherent to vascular endothelium in the presence of chemotherapy than are healthy RBCs from both white and African-American women without SCT. To test the hypothesis, we will pursue the following two specific aims: Assess for baseline differences in RBC adhesion to endothelial proteins among white women as compared to African-American women– We will measure the change in quantity and strength of adhesive interactions between single RBCs and endothelial proteins. The influence of race and SCT-status will be examined. Test the in vitro effect of chemotherapy on RBC adhesion to endothelial proteins among white women as compared to African-American women – We will measure the in vitro effect of chemotherapy on single RBC adhesion to endothelial proteins. The influence of race and SCT-status will be examined.
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. 14-141-6 (Dr. Jayesh Kamath, PI): A Text Messaging Intervention to Improve Psychiatric Treatment Adherence: A Proof-of-Principle Study
Lack of adherence to psychiatric treatment is prevalent and problematic. Between 1/3 to 1/2 of patients on psychotropic medications are not adherent to prescription regimes and about 50% of psychiatric services appointments are no-shows. Low treatment adherence is associated with greater risk of emergency department use and hospitalization. It’s been estimated that antipsychotic non-adherence alone is responsible for about $1.5 billion in annual hospital costs in the US. Among reasons for non-adherence identified in the literature, forgetting is most commonly cited. Other factors include perceived social support, perceived therapeutic alliance, younger age, male gender, and ethnic minority background. Low cost interventions are needed to increase psychiatric treatment adherence that are responsive to known reasons for low adherence. A growing body of research demonstrates improvements in treatment adherence and clinical outcomes associated with similar text messaging interventions; however few studies have been conducted with psychiatric patients. Given the potential for improvements in health and cost savings, the proposed pilot study holds great promise for reward. We view the proposed work as an important first step leading to larger external funding and forming the core of a research collaboration that we hope to expand, particularly for the justice-involved. We have identified multiple opportunities for growing the research project within UConn and throughout the community.
IRB No. 14-162-2 (Dr. Patricia Diaz, PI): The prevalence of culturable and non-culturable fungi among patients with cancer undergoing chemotherapy treatment alone or in combination with head neck radiotherapy and non-cancer controls
To conduct a pilot comparison of the prevalence and abundance of culturable and non-culturable fungi among individuals diagnosed with cancer (during the course of chemotherapy alone or combined with head and neck radiation therapy) and non-cancer subjects.
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. 14-181-1 (Dr. Jayesh Kamath, PI): Implementation of an Evidence Based PTSD Treatment in Public Sector Settings
This research study will be looking at treatment for post-traumatic stress disorder (PTSD) resulting from experiencing interpersonal violence. The researchers hope to learn whether a flexibly applied cognitive behavioral treatment for PTSD called Skills Training in Affective and Interpersonal Regulation / Narrative Therapy (STAIR/NT) is more effective than the psychotherapy usually provided in the clinic, which is called Treatment as Usual or TAU. STAIR/NT Cognitive-behavior therapy. The cognitive-behavioral therapy used in this study has been shown to be helpful for people with PTSD and other problems which resulted from interpersonal trauma. It works with people's emotions and thoughts related to trauma and helps them create more effective ways of living and interacting with others. We have evidence suggesting that flexible application of the treatment provides the same benefits as a strict order of sessions. Subjects assigned to cognitive-behavioral therapy, subjects and therapists will work together to make decisions about how to use the cognitive-behavioral treatment. The treatment can have as few as 16 sessions and as many as 24 sessions. The sessions will be scheduled once a week and will last 45 minutes. In collaboration with the therapist, subjects can choose to repeat specific activities from a session or to skip them, depending on whether they and the therapist think that these activities will be helpful. There are some basic minimum requirements in the use of the therapy. The first is that the subject complete the activities of the treatment in the following order and have the following minimum number of sessions specific to three types of sessions. Specifically, the treatment requires (1) three sessions of skills training in emotion management, (2) four sessions of social skills training and (3) five sessions which involve the discussion of the trauma and specific thoughts and beliefs related to the trauma. Treatment As Usual. Subjects randomized to Treatment As Usual (TAU), will receive the treatment that the clinic routinely gives to clients. The treatment will occur weekly. The duration of the treatment will depend on how decisions about treatment length are usually decided at the clinic. The treatment will last no longer than the 12 months of the study. Regardless of the treatment subjects receive, they will be asked to give a complete psychiatric and medical history and may be asked to obtain records of medical and psychiatric history.
IRB No. 14-197-6 (Dr. Damion Grasso, PI): The Influence of Prenatal Exposure to Stress on the DNA Methylation Status of FKBP5 in Newborns
Understanding the impact of prenatal maternal stress (PNMS) on child development is needed to identify at-risk children at the earliest possible time point and to design and implement effective interventions. One of the genes involved in the stress response pathway is FKBP5 (FK506 binding protein 5). The FKBP5 protein is a critical component of a negative feedback loop that functions to terminate the stress response at the cellular level by decreasing ligand binding and blocking translocation of the glucocorticoid receptor complex into the nucleus. Emerging data on FKBP5 suggests one potential pathway by which early, chronic childhood trauma exposure may lead to emotional and behavioral problems later in life. This study seeks to understand how the in utero exposure to domestic violence can impact ability of this gene to function properly.
IRB No. 15-067-6 (Dr. Golda Ginsburg, PI): Enhancing the Capacity of School Nurses to Reduce Anxiety in Children (CALM)
Childhood anxiety is pervasive (affecting up to 20% of youth) and associated with adverse academic, social, and other long-term consequences. These devastating outcomes can be averted by enhancing children’s access to mental health services. Expanding the network of mental health providers to include nurses represents an important- and innovative- step in disseminating evidence-based interventions for improving academic outcomes of children. Given that children with early anxiety symptoms frequently visit the school nurse due to physical symptoms or to avoid anxiety-provoking situations, school nurses are often the first point of contact and are, therefore, well-positioned to identify and intervene early with these children. The primary aim of this study is to enhance the capacity of school nurses by developing and refining a novel nurse-administered intervention (CALM; Child Anxiety Learning Modules) designed to reduce anxiety symptoms and improve academic, social, and behavioral functioning and to assess its feasibility, fidelity, and promise in a school setting. The end product of this project will be a fully developed intervention with evidence of feasibility in the school setting and pilot data to support the intervention’s promise in reducing anxiety and improving academic functioning. If succcessful, a larger randomized controlled trial to fully evaluate the interventions efficacy will be conducted.
IRB No. DORN004127 (Dr. Cheryl Oncken, PI): The Menthol Research Study – Manipulating Tobacco Constituents in Female Menthol Smokers
The FDA could reduce the amount of nicotine in cigarettes, or ban menthol from cigarettes. Investigators from Hartford Hospital and the University of Connecticut Health Center are examining the effect of switching to low nicotine or menthol cigarettes on smoking behavior. This study will look at: 1. How reducing nicotine and or menthol in cigarettes can affect the appeal of smoking & quit rates. 2. The amount of toxicant exposure a woman gets from cigarettes. 3. The ways in which cigarette content changes may decrease smoking behavior. 4. How genetic variations in a taste & smell sensitivity may effect tolerability of experimental cigarettes, smoking satisfaction, and smoking behavior. Study Involvement Requires switching to one of the following types of cigarettes for 6 weeks: 1) Low nicotine + NO menthol 2) Low nicotine + menthol 3) Regular nicotine cigarettes + NO menthol 4) Your own brand of nicotine + menthol All participants attend 11 study visits. Participants may receive: *Study cigarettes x 6 weeks *$20 per study visit.
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. 15-118-1 (Dr. Bruce Strober, PI): A Phase 3, Multicenter, Randomized, Double-blind, Placebo and Active Comparator-controlled Study Evaluating the Efficacy and Safety of Guselkumab for the Treatment of Subjects with Moderate to Severe Plaque-type Psoriasis (VOYAGE 1)
Study description not available
IRB No. 15-115-1 (Dr. Santhanam Lakshminarayanan, PI): A Randomized, Double-Blind, Placebo-Controlled Phase II Study to Investigate the Efficacy and Safety of Riociguat in Patients with Diffuse Cutaneous Systemic Sclerosis (dcSSc)
The purpose of this study is to investigate the effectiveness and safety of riociguat (BAY 63-2521) in patients with diffuse cutaneous systemic sclerosis. It is approved by the FDA for the treatment of 2 forms of hypertension in lung blood vessels, chronic thromboembolic pulmonary hypertension (CTEPH) and pulmonary arterial hypertension (PAH). Riociguat works by stimulating an enzyme in cells, which increases the production of another molecule. The resulting effects are a decrease in tissue fibrosis and relaxation of smooth muscle cells (cells found in particular internal organs and blood vessels). It is proposed that riociguat may offer protection against worsening diffuse cutaneous systemic sclerosis.
IRB No. 15-077-1 (Dr. Jessica Clement, 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. 15-186-1 (Dr. Efthimia Ioannidou, PI): A PILOT STUDY TO INVESTIGATE THE EFFECT OF VARIOUS CPC CONCENTRATIONS ON GINGIVITIS IN A SPLIT-MOUTH DESIGN
The purpose of this randomized, controlled, parallel arm clinical research study is to assess the effect of anti-plaque mouth rinses on gum disease. To achieve this goal, the study will compare two mouth rinses with different Cetylpyridnicium Chloride (CPC) dose to a negative control (water). CPC is an antiseptic that kills bacteria in the dental plaque. This study will also be evaluating the effect of dental cleaning in combination with CPC.
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. 16-007-1 (Dr. Upendra Hegde, PI): A Phase 3 Clinical Trial of Pembrolizumab (MK-3475) in First Line Treatment of Recurrent/Metastatic Head and Neck Squamous Cell Carcinoma
Head and neck cancer describes a range of tumors that arise in the head and neck region, which includes the oral cavity, pharynx, larynx, nasal cavity, paranasal sinuses, thyroid, and salivary glands. The worldwide incidence of head and neck cancer exceeds half a million cases annually, ranking it as the fifth most common cancer worldwide, and accounts for 5% of all malignancies. A large number of patients with head and neck cancer initially present with locally advanced, stage III/IV disease that is initially treated with combinations of chemotherapy, radiation and/or surgery. This initial treatment is generally designated as "definitive" therapy, which typically combines chemoradiation and surgery and can result in disease control rates ranging between 33 and 86% of patients. Patients who progress after initial definitive therapy require subsequent treatment for recurrent (R) disease. Patients who initially present with metastatic (M) disease generally receive the same therapy as those with recurrent disease after definitive treatment. In this trial, subjects with oropharynx cancer will be stratified by HPV status (positive or negative). The favorable prognostic significance of HPV-positive head and neck cancers in the oropharynx has been increasingly established. Preliminary data of single agent pembrolizumab in head and neck cancer patients in KEYNOTE-012 demonstrate efficacy in both HPV-positive and HPV-negative patients. Investigator site assessment of HPV using immunohistochemistry (IHC) staining for the p16 protein will be used for the subjects with oropharyngeal cancer prior to randomization. Study design This is a randomized, active-controlled, multi-site, open-label trial of pembrolizumab, or pembrolizumab plus platinum plus 5-FU chemotherapies versus platinum plus 5-FU plus cetuximab in subjects with advanced head and neck cancer. Study population and sample size Subjects with recurrent or metastatic Head and Neck Squamous Cell Carcinoma. Approximately 750 subjects will be enrolled. Major Study Interventions (1) Pembrolizumab (MK-3475) 200 mg every 3 weeks; or (2) Pembrolizumab (MK-3475) 200 mg every 3 weeks + Platinum + 5- Fluorouracil (5-FU); or (3) Cetuximab 400 mg/m2 initial dose followed by 250 mg/m2 (weekly) + Platinum + 5FU (Platinum is either Cisplatin 100 mg/m2 Q3W or Carboplatin AUC 5 Q3W; 5FU is 1000 mg/m2 continuous from Day 1 to Day 4 Q3W) Main Outcome Measures/Analyses Primary Objectives (1) Objective: To compare the Progression Free Survival (PFS) per RECIST 1.1 as assessed by central radiologists' review in a subgroup of first line recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) subjects with strongly positive PD-L1 expression, treated with Pembrolizumab monotherapy versus standard treatment cetuximab with chemotherapy. (2) Objective: To compare the Progression Free Survival (PFS) per RECIST 1.1 as assessed by central radiologists' review in subjects with first line R/M HNSCC treated with pembrolizumab monotherapy or a combination of Pembrolizumab with chemotherapy versus standard treatment cetuximab with chemotherapy.
IRB No. 16-086-1 (Dr. Kai Chen, PI): Endothelial Dysfunction in Coronary Artery Disease and Diastolic Heart Failure
Congestive Heart failure, including systolic and diastolic heart failure, is a major public health hazard and its prevalence continues to rise. While the mortality of systolic heart failure has significantly reduced over the past decade thanks to the advances in pharmacological therapy, there has not been a single therapy that has shown to be survival benefit on diastolic heart failure. A significant gap in knowledge on diastolic heart failure has to be bridged before we may design a therapeutic strategy to target this disease. Recent elegant studies have revealed evidence of systemic and myocardial inflammation in endomyocardial tissues. A new paradigm of the pathophysiology of diastolic heart failure has been proposed - systemic proinflammatory state, coronary endothelial inflammation, impairment in endothelial-cardiomyocyte nitric oxide signaling, inflammatory cell infiltration and proinflammatory cytokines, collectively lead to diastolic dysfunction. Therefore, our central hypothesis is endothelial dysfunction contributes to diastolic function and clinical exacerbation of heart failure.
IRB No. 16-111-1 (Dr. Efthimia Ioannidou, PI): Novel Paradigm to Improve Inflammatory Burden in ERSD
The study proposes to examine, for the first time in dialysis patients, the short and long-term effect of systemic and repeated oral health interventions on inflammation and clinical oral parameters. The ultimate goal of this proposal is to improve access to oral care and quality of life by implementing continuous and repeated in-center oral health programs in dialysis populations.
IRB No. 16-098-1 (Dr. Jayesh Kamath, PI): A 12-Month Randomized, Open-Label Study of Caregiver Psycho-education and Skills Training in Patients Recently Diagnosed with Schizophrenia, Schizoaffective Disorder, or Schizophreniform Disorder and Receiving Paliperidone Palmitate or Oral Antipsychotic Treatment. Family Intervention in Recent onset Schizophrenia Treatment (FIRST)
Family education and training has been shown to have a positive impact on both the individual with psychosis and their caregivers when it is embedded within a treatment program. Providing support to caregivers to help make them be more active and effective participants in the patient's recovery can be a cost-effective approach that contributes to better patient outcomes. This study will enroll patients recently diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder that are prescribed either paliperidone palmitate or oral antipsychotic treatment, and their designated caregivers. Outcomes in patients with caregivers receiving a study-provided psycho-education and skills training program will be compared to patients with caregivers receiving usual caregiver support (caregiver support that is customarily provided by the study site, if any). OBJECTIVE AND HYPOTHESES Primary Objective: To evaluate the overall effect of caregivers receiving a study-provided caregiver psycho-education and skills training program on the number of treatment failures (psychiatric hospitalization, psychiatric ER visit, crisis center visit, mobile crisis unit intervention, arrest/incarceration, and suicide or suicide attempt) in patients under their care during a 12 month period. Primary Hypothesis: When caregivers receive a study-provided psycho-education and skills training, patients with schizophrenia, schizoaffective disorder, and schizophreniform disorder under their care will have fewer treatment failures compared with patients whose caregivers receive usual caregiver support. Secondary Hypotheses: Over a 12 month period study-provided caregiver psycho-education and skills training will be superior to usual caregiver support in reducing caregiver burden and distress. Patients diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder receiving oral antipsychotic treatment and who have caregivers receiving a study-provided caregiver psycho-education and skills training program will have fewer treatment failures compared with patients receiving oral antipsychotic treatment that have caregivers receiving usual caregiver support. Patients diagnosed with schizophrenia, schizoaffective disorder, or schizophreniform disorder receiving paliperidone palmitate treatment and who have caregivers receiving study-provided caregiver psycho-education and skills training program will have fewer treatment failures compared with patients receiving paliperidone palmitate that have caregivers receiving usual caregiver support.
IRB No. 16-124-1 (Dr. Jessica Clement, 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. 16-210-6 (Dr. Biree Andemariam, PI): 3D Microscopic Imaging to Differentiate Healthy vs Diseased Red Blood Cells
This study is a prospective, clinical/translational research study using peripheral blood from consenting SCD patients and healthy control volunteers. From our earlier experiments with red blood cells using the 3D microscope, we have found that the mechanics of cell membrane fluctuations are very sensitive to the state of health of the cell. Parameters extracted from the dynamic imaging of the cell (amplitude of cell membrane fluctuation, frequency of cell membrane fluctuation, volume fluctuation and dynamic light scattering) can be used to discriminate healthy and diseased cells. The present study is aimed at collecting dynamic information of healthy versus diseased cells to quantify mechanical properties and estimate the state of health of the cells as well as the effectiveness of the developed 3D microscope in automatic identification of diseases. We hypothesize that the 3D microscope will be able to discriminate between healthy and sickle cell disease red blood cells, a tool that will have practical use in diagnosis and treatment of the disease. We will enroll both healthy and sickle cell disease adults who are 18 years of age and older who have not had a transfusion in the past 3 months.
IRB No. 16-220-1 (Dr. Jayesh Kamath, 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. 17-066-3 (Dr. Augustus Mazzocca, PI): Factors Influencing Successful Non-operative Management of Patients with Acromioclavicular Joint Dislocations
This study will examine the outcomes of patients who had an acromioclavicular (AC) joint dislocation at least two years ago and were initially treated without surgery by Dr. Augustus Mazzocca. A survey will be used to collect updated post-treatment outcome information from patients regarding the current condition, symptoms and functioning of the injured shoulder. A chart review will be conducted to collect demographic and clinical information including injury, treatment and, where applicable, intra-operative details. Retrospective and prospective data will be examined to determine the factors associated with positive outcomes.
IRB No. 16-212-1 (Dr. Santhanam Lakshminarayanan, PI): A Phase II, randomized, double-blind, placebo controlled, parallel-group, multicenter trial to evaluate the efficacy and safety of abituzumab in subjects with systemic sclerosis-associated interstitial lung disease (SSc-ILD)
Abituzumab is an investigational drug that is being evaluated for the treatment of patients with systemic sclerosis (SSc)-associated interstitial lung disease (SSc-ILD). SSc is an autoimmune disease that can affect many organs, including the stomach, intestines, heart, and lungs. In general, SSc causes hardening of the skin and organs. SSc-ILD involves damage to lung tissue and can cause difficulty breathing and worsening lung function.
IRB No. 17-045-2 (Dr. Mario Perez, PI): The Airway Inflammatory Profile of E-Cigarette Users
Study objective: The research study is about how the human body, particularly the airways, react to the regular use of e-cigarettes. The purpose is to show that regular use of e-cigarettes can be associated with airway inflammation in the sputum of regular users of e-cig. We intend to study if the regular use of e-cig, in a simliar way to conventional cigarettes, can trigger an inflammatory response in the airways. Hypotheses: 1. subjects who use e-cigarettes have evidence of airway inflammation when compared to healthy non-smoker subjects 2. Subjects who smoke regular tobacco cigarettes have evidence of more airway inflammation than e-cigarette users. 3. Subjects who use e-cigs with flavoring, e.g. chocolate, or regular cigarettes with flavoring (e.g. menthol) will have more airway inflammation than e-cig and regular cigarette users who don't use flavored products, e.g. menthol. Aims: 1. We plan to characterize airway inflammation profile in e-cig users compared to healthy non-smokers 2. We plan to characterize the airway inlfammatory profile of tobacco cigarette smokers compared to e-cig users. 3. We plan to characterize the effect of menthol in e-cigarettes and tobacco cigarettes on the airway inflammatory profile.
IRB No. 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. 14-041HO-1 (Dr. Rajesh Lalla, PI): Clinical Registry of Dental Outcomes in Head and Neck Cancer Patients (ORARAD)
The ORARAD study is a prospective cohort study to document dental and other oral outcomes in patients who receive radiation therapy as part of treatment for a head and neck cancer. Seven hundred and fifty-six participants will be enrolled nationally over a three year period. Of these, 135 will be enrolled at UCHC. All participants will be seen for the study before starting radiation therapy then at six-month intervals for up to two years after the start of radiation therapy. The primary outcome will be the two-year rate of tooth loss after radiation therapy. Secondary outcomes will include measures of dental caries, periodontal health, salivary flow, and exposed bone/osteoradionecrosis.
IRB No. 17-072-6 (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. 17-024-1 (Dr. Craig Rodner, PI): Clinical and Radiographic Outcome Following Management of Benign Lesions of the Hand and Wrist with Calcium Phosphate Bone Cement
Traditional treatment for benign tumors of the hand and wrist involves curettage to remove the tumor. Following removal, the hand is typically reconstructed with autograft or allograft tissue. Due to concerns of donor site morbidity with autografts and immunogenicity with allografts, there has been a shift towards using various types of bone graft substitute to fill the void after bone tumor removal. Calcium phosphate bone cement is an alternative to allograft or autograft bone following curettage in the treatment of benign hand and wrist tumors. Few studies have reported patient outcomes following treatment with calcium phosphate bone cement grafting following curettage for treatment of enchondroma of the hand and those that have included several patients with pathologic fractures, which required fixation. The purpose of this study is to examine the long-term outcome of patients who were treated with calcium-phosphate bone cement for benign lesions in the hand and wrist without pathologic fractures. This is a one time study visit. Patient reported outcome measures, physical exam finding, and a radiographic assessment will be used to evaluate the success of this procedure.
IRB No. 17-021S-1 (Dr. Richard Fortinsky, PI): Care Management for Cognitively Vulnerable Older Adults
The purpose of the study is to compare ways to support the health of people over age 65 who may be experiencing signs of memory problems, feelings of sadness, or feelings of confusion. The study will look at how nurses, social workers and other health care professionals can help older adults get the care they need and to stay as healthy as possible. This type of support provided by these healthcare professionals is called "care management services". The study will compare two different care management teams: "Home Based Care Team" and "Telephone Based Care Team". The "Home Based Care Team" (HBCT) is composed of a nurse practitioner who is specifically trained to provide care and psychosocial support to older adults, social worker, physical and occupational therapists, registered dietician, pharmacist and community health educator. The Home Based Care Team nurse practitioner will lead this care management team. Interaction with the team will primarily take place within the older adult's home. The "Telephone Based Care Team" (TBCT) is composed of a nurse care manager who will assess the older adult's current health status and provide referrals to other healthcare professionals as needed. Interaction with the "Telephone Based Care Team" will primarily take place over the phone.
IRB No. 16-148-3.1 (Dr. Jonathan Covault, PI): Zonisamide treatment of Alcohol Use Disorder: An Evaluation of Efficacy and Mechanism of Action
Alcohol use disorders (AUDs) are highly prevalent (lifetime prevalence estimated to be >30% in the U.S. general population, and >40% in military veterans) and have large detrimental impacts on patients, their families and society. The number of FDA-approved medication treatments for alcoholism is limited in number (naltrexone, acamprosate, disulfiram) and have only modest effects. Anticonvulsant (anti-epileptic) medications have shown evidence of efficacy in treating alcoholism. Zonisamide (ZNS) is an anticonvulsant and a promising potential treatment for AUDs. Zonisamide reduces drinking, craving for alcohol, and anxiety in subjects with AUDs. We (Arias, Feinn, Oncken, Covault, and Kranzler. 2010) completed a randomized, placebo-controlled pilot trial of zonisamide for treating alcohol dependence, which showed reductions in heavy drinking, overall drinking, and alcohol craving with the medication. Zonisamide was very well tolerated in the pilot study. Recently, another small placebo-controlled trial of zonisamide showed advantages of the medication over placebo in reducing drinking. However, no definitive study of ZNS treatment for alcoholism has been performed. In this study we will test if the medication zonisamide can reduce harmful drinking patterns, and try to determine whether medication response can be predicted by a few key factors such as genotype, age of onset of alcoholism (early vs. late), or stress-reactivity. This study includes an innovative pharmacogenomics secondary component that examines whether the total number of risk alleles for a panel of previously identified alcohol use and stress response risk alleles is associated with treatment response. The study is funded by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) via a grant to Dr. Arias at Yale University and seeks to recruit 160 subjects across 2 clinical sites (West Haven VA Alcohol Research Center and UConn Health Center). Understanding how ZNS works, and for whom it works best, will advance pharmacologic treatment for alcohol use disorders and bring us closer to personalized treatment.
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. 15-006-3.1 (Dr. George Kuchel, PI): Immune Response to High-Dose vs. Standard Dose Influenza Vaccine
This is a 5-year randomized study of split-virus influenza vaccine (SVV) in a high-dose (HD) vs. standard dose (SD) formulation in each of five influenza seasons to define the key determinants of vaccine-mediated protection against influenza and how these immunologic mediators may be enhanced by vaccination with a U.S. approved high-dose influenza vaccine in older people. Trial Objectives The strategic objectives of this proposal are to conduct a randomized study of the U.S. approved SD-SVV vs. HD-SVV to establish GrzB activity and the IFN :IL-10 ratio in influenza-stimulated PBMC as biomarkers of clinical protection against the serious complications of influenza infection; develop a clinical tool (frailty index) and biomarkers (CMV status and bGrzB activity) for use in point-of-care testing to predict the response to influenza vaccination and appropriately target other prevention strategies to reduce the impact of influenza illness in particularly vulnerable older people; and translate these findings to testing new vaccines for their potential to significantly enhance protection against the serious complications of influenza in older adults. In the process, we will determine whether the Frailty Index [31], as a predictor of functional decline and mortality [32], can be used as point-of-care testing in the management of influenza. Table 1 summarizes the 5-year plan. The experimental design incorporates extensive experience in measuring T-cell responses to influenza vaccination and a study design that reflects an understanding of the variables that contribute to the heterogeneity of health and frailty in older adults. The overall experimental plan is described in three sections including a) Study Populations, b) Experimental Design including the Overall study protocol and Specific Aims 1-3), and c) Tests and Assays. Study Hypothesis (Aim 1) Determine whether a high dose vaccine performs better than standard doses Study Hypothesis (Aim 2): Evaluate the association of degree of frailty to cytomegalovirus (CMV) status and bGrzB levels in resting T cells. Study Hypothesis (Aim 3): Establish predictors of vaccine-mediated protection that can be developed for point-of-care testing
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. 16-227-3.1 (Dr. Upendra Hegde, PI): A PHASE 1, OPEN-LABEL, DOSE ESCALATION STUDY OF PF-04518600 AS A SINGLE AGENT AND IN COMBINATION WITH PF-05082566 IN PATIENTS WITH SELECTED LOCALLY ADVANCED OR METASTATIC CARCINOMAS
Background: PF-04518600 and PF-05082566 are antibodies (a type of protein) which have been shown to stimulate the immune system. Research has shown that an immune response like this can work against tumor cells to slow tumor growth by causing tumor cells to die. PF-04518600 alone and in combination with PF-05082566 are being investigated as possible treatments for patients with advanced liver, skin (melanoma), kidney, head and neck, stomach, cervical, gastric, bladder or lung cancer. Rationale for this study: The ability to escape immune recognition is a hallmark of cancer progression. By manipulating the immune system and restoring immune surveillance, immunotherapy offers the opportunity to not only eradicate or stop tumor growth, but also the opportunity to decrease the rate of recurrence.1 One strategy for increasing tumor immunity would be to activate and expand tumor-associated antigen T cells. It has long been recognized that T cell activation is not mediated by antigen stimulation alone. Indeed, tumor antigens may induce T-cell anergy, rendering T cells unable to proliferate in response to antigen, and hypo-responsive to further antigen encounter. Instead, co-stimulatory receptors are required to complete the process of T cell activation and expansion. Thus, co-stimulatory receptors may have the potential to prevent tumor-induced immune tolerance. PF-04518600 is a fully human Immunoglobulin G2 (IgG2) agonistic monoclonal antibody that is highly selective for human OX40 (CD134). PF-04518600’s agonistic potential was revealed in a 293 luciferase reporter assay, whereby induced OX40 mediated NFkB activation, and luciferase activity increased dose proportionally to increasing concentrations of PF-04518600. Selectivity studies using a biacore assay also revealed PF-04518600 to be highly selective for OX40, with no cross activity with other members of the TNFR super-family, including CD40 receptor, 4-1BB receptor (CD137) and glucocorticoid-induced TNFR family related gene (GITR). Study Design: This is a Phase 1, open label unblinded manner, multi-center, multiple dose, dose escalation, safety,pharmacokinetic, and pharmacodynamic study of PF-04518600 monotherapy (Part A) and PF-04518600 plus PF-05082566 combination therapy (Part B). Both Part A and Part B will be further divided into a dose escalation phase, and a dose expansion phase. Study Population and Sample Size: Adults (men and women) age 18 years and over. Patients with histological or cytological diagnosis of HNSCC, HCC, melanoma, clear cell RCC urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix. A maximum of approximately 190 patients are expected to be enrolled into the study. Major Study Interventions: For monotherapy, patients will be dosed at 0.01 mg/kg PF-04518600 in the first cohort. For combination therapy, patients will be dosed at 0.1 mg/kg PF-04518600 and 20 mg PF-05082566 in the first dose combination level. Main Outcome measures /Analyses: To assess safety, and tolerability at increasing dose levels of PF-04518600 in patients with selected advanced or metastatic solid tumors in order to establish the MTD. Primary Objectives: -To establish the RP2D of PF-04518600 in patients with selected advanced or metastatic solid tumors. To further characterize the safety and tolerability of PF-04518600 in patients with selected advanced or metastatic solid tumors. Secondary Objectives: -To assess preliminary anti-tumor clinical activity of PF-04518600 in patients with selected advanced or metastatic solid tumors solid tumors. To characterize the single dose and multiple dose PK of PF-04518600 following IV administration. -To characterize the degree of TE by PF-04518600 at multiple doses
IRB No. 14-184-3.2 (Dr. Jessica Clement, PI): A Phase II, Multicenter, Single-Arm Study of Atezolizumab in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer
The purpose of this study is to look at the effects, good or bad, of MPDL3280A on you and your bladder cancer. MPDL3280A is an experimental drug, which means that health authorities have not approved MPDL3280A for the treatment of bladder cancer. MPDL3280A is an antibody (a protein produced by the body's immune system) that affects the immune system by blocking the programmed death-ligand 1 (PD-L1) pathway. The PD-L1 pathway is involved in regulating the body's natural immune response, but tumors can take advantage of this regulation to partially resist or evade the immune system. By blocking the PD L1 pathway, MPDL3280A may help your immune system stop or reverse the growth of tumors. Blood, tissue samples, and related medical information collected during this study will be used by Sponsor researchers and other researchers partnering with the Sponsor for research related to bladder cancer and how MPDL3280A works.
IRB No. 17-013-6 (Dr. Susan Tannenbaum, PI): Retrospective study to investigate clinical utility of BIOARRAY Therapeutics genomic panel as a predictor of pathological response in breast cancer patients treated with taxane-based neoadjuvant chemotherapy as well as in patients who have developed metastatic disease.
In our study we are partnering with BIOARRAY Therapeutics. It is a biotechnology company that has developed a genomic profiling test based algorithm. This algorithm can predict response in breast cancer patients when treated with taxane-based chemotherapy. This information can help physicians personalize treatments upfront. The goal of this study is to validate using retrospective samples, the ability to predict response based on their BIOARRAY test profile.
IRB No. 15-164S-3.2 (Dr. Julie Wagner, PI): Diabetes Risk Reduction through Eat,Walk,Sleep And Medication Therapy Management for Depressed Cambodians (DREAM)
Diabetes Risk Reduction through Eat, Walk, Sleep And Medication Therapy Management for Depressed Cambodians (DREAM) This project is designed to reduce risk for diabetes in Cambodian Americans with depression. 210 Cambodian Americans in southern New England will be screened for their diabetes risk as well as depression; those at risk for diabetes with depression will be enrolled. This study will determine the effect of Lifestyle Modification vs Lifestyle + Medication Therapy Management (MTM) vs Supportive Services Control. Assessments gather data such as sleep, activity, anthropometrics, mental health symptoms, and medications at baseline, 1year and 2years. Blood tests will be performed on the same schedule for glucose, insulin, and inflammation. Hair samples will be obtained on the same schedule for levels of cortisol Cambodian Americans have been previously studied by these Investigators who found that found 50% of this group (over age 35) have 5 or more chronic diseases including heart attack, chronic depression and/ or PTSD. Their rates of diseases like diabetes, hypertension and high cholesterol are twice those of national averages. Overall Cambodian health status in the US is worse than other Asian refugee groups resettled in the US from their refugee camps. The Diabetes Prevention Program (DPP) has shown that disease onset can be delayed or even prevented by lifestyle modification programs such as that to be provided here. The KHA agency is a partner with the National Diabetes Education Program and committed to overcoming care barriers which underserved communities face. Such programs help mitigate depression by activating and engaging their clients. This PI & Team will utilize Community Health Workers (CHW) to conduct the research and deliver the lifestyle program called Eat, Walk, Sleep. 1/3 of the subjects will receive EWS which has been specifically tailored for the unique language and cultural considerations in this group.The PI has previously done a similar diabetes education intervention with non english speaking Latinos with low literacy- delivered in an ethnic agency setting by CHWs, including home and group participation. For 1/3, EWS is combined with secure pharmacist (Medication Therapy Management-MTM) videoconferencing interactions at home. 1/3 (70 subjects) 1/3 will receive control/Supportive Services Group- will receive Enhanced Standard CHW support/services referral, while undergoing the same initial evaluation assessments . The researchers seek to determine that lifestyle intervention will produce greater improvement in risk factiors and that biologic factors-waist size,blood pressure, diabetes marker- HgBA1c, and others are improved.
IRB No. 18-076-3 (Dr. Mohamad Halawi, PI): Real-Time Three-Dimensional Analysis of Acetabular Kinematics: Bridging the Gap to Patient-Specific Total Hip Replacement
The purpose of the study is to enhance our understanding of hip biomechanics (human structures and movement) during activities of daily living. Three-dimensional motion analysis will be performed in "healthy" volunteers (no history of degenerative disease or functional limitations in the lumbar spine, hips, or knees that may affect normal gait in either lower extremity) and in patients with degenerative joint disease before and after total hip arthroplasty. This knowledge is intended to improve the treatment and outcomes of degenerative disease of the hip.
IRB No. 18-093-1 (Dr. Mohamad Halawi, PI): Efficacy and Cost-effectiveness of Intra-Articular Ketorolac Injection for Knee Osteoarthritis: A Randomized, Controlled, Double-Blinded Study
Hypothesis: Ketorolac injection is a cost-effective adjunct in the nonoperative treatment of knee osteoarthritis (OA) compared to steroids and viscosupplementation. Aims/objectives: The objective of this randomized, controlled, double-blinded, prospective study is to assess the efficacy and cost-effectiveness of knee injection with ketorolac in the nonsurgical management of symptomatic OA compared to injections with corticosteroids and viscosupplements.
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. 18-001-2 (Dr. Lauren Geaney, PI): Evaluating an Objective Measure of Diagnostic Ankle Arthroscopy Skills
This is a pilot study for a new arthroscopic skill evaluation tool. Participants will be asked to perform an arthroscopic procedure on a cadaver ankle while being observed. Participants will also be asked to answer questions about themselves and their knowledge of orthopedic surgery via a short questionnaire, self-evaluation and oral examination. The single session should last about 30-40 minutes in the arthroscopy teaching laboratory in the Medical Academic Research Building (MARB).
IRB No. 18-122-2 (Dr. Robert Arciero, PI): Utility of Intraoperative Radiograph to Confirm Position of Suspensory Fixation
Suspensory fixation of anterior cruciate ligament (ACL) graft has emerged as a good option femoral graft fixation. It offers the advantage of technical ease and speed while providing a secure fixation. However, there are numerous examples in the literature of improper deployment of the fixation leading to tissue interposition between the button and bone. A poorly deployed button can cause inadequate fixation, which has been shown to lead to graft migration and pain. Occasionally, revision surgery is required to fix these complications. Despite the documented potential for complication, many surgeons do not confirm the correct position of their fixation with radiograph but instead rely on manual testing for a "hard stop" to confirm positioning. This manual testing is performed by tugging on the graft after the fixation is deployed and considering the button to be in the correct position when there is a hard stop, or no more give to the graft. The authors believe that this commonly employed method may be inadequate to determine correct button position. We believe that, after it appears the button is in a correct position by manual testing, an intraoperative radiograph will often demonstrate tissue interposition between the button and bone.
IRB No. 17-124-3.1 (Dr. Robert Arciero, PI): Mid and Long-Term Outcomes for Patients Treated with Distal Femoral Osteotomy
We are interested in how patients are doing who had distal femoral osteotomy surgery. This knowledge may help to improve the treatment and outcomes of future patients who experience knee malalignment. Therefore, we are conducting a research study and inviting participation from all patients treated by Robert A. Arciero, MD and Thomas M. DeBerardino, MD who had a distal femoral osteotomy at least two years ago. This is a case series study with three distinct parts: (1) a limited retrospective chart review, (2) a prospective survey and detailed retrospective chart review for responders, and (3) a detailed retrospective chart review for non-responders. The purpose of the limited retrospective chart review is to collect the minimum information necessary to determine eligibility and to contact eligible patients. Then, eligible patients will be contacted to invite participation in the prospective survey and detailed retrospective chart review. For patients who respond, the survey is used to collect postoperative outcome information regarding current pain, satisfaction and functional outcomes. Patients who respond will also be included in a detailed retrospective chart review to collect information regarding demographics, preoperative clinical factors, radiographs and the DFO procedure in order to examine relationships between preoperative and operative findings as well as the postoperative outcomes collected during the prospective survey. Patients who do not respond by enrollment closure will be considered lost to follow-up. A second detailed retrospective chart review will be performed to include these non-responders in order to adequately characterize the study population and to determine whether there are differences in the distribution of clinical or demographic variables.
IRB No. 16-211-3.1 (Dr. Mark Litt, PI): Individualized Assessment and Treatment Program for Alcoholism: Treatment and Mechanisms
Through our 2009 R-21 pilot project we developed a cellphone-based experience sampling (ES) procedure that assesses, in near real time, coping skills and associated thoughts and feelings that contribute to preventing relapse in alcoholics in treatment. We propose using the experience sampling procedure prior to treatment to collect data on thoughts, feelings and behaviors that patients have when they encounter drinking situations in real life. This information will be used by a therapist tailoring an individualized cognitive-behavioral treatment for each particular patient. The individualized assessment and treatment program (IATP) will be compared to a more conventional packaged cognitive-behavioral treatment (PCBT), and to a Case Management Control condition (CaseM). 207 men and women meeting criteria for alcohol use disorder will be randomly assigned to 12 weekly sessions of either CaseM, PCBT or IATP. Follow-ups will be conducted at posttreatment, and at 3-month intervals out to 27 months. The use of momentary assessments of thoughts, feelings and behaviors will allow us to determine what patients are actually doing, in close to real time, to initiate and maintain their own sobriety. The use of experience sampling in the follow-up period will allow us to determine whether the mechanisms that were active in initiation and early maintenance continue to be active in maintaining long-term abstinence. By comparing IATP with CaseM and PCBT we will be able to control for the general effects of study participation (i.e., "common factors"), the effects of being in a treatment study and receiving manualized treatment, general skills training (psychoeducation), and therapist presence.
IRB No. 13-087-3.2 (Dr. Susan Tannenbaum, PI): Factors Influencing Fatigue in Breast Cancer Patients Undergoing Breast Irradiation
Study description not available
IRB No. 17-115-3.2 (Dr. Kai Chen, PI): The Risk Factors and Imaging Study of Diastolic Dysfunction
A normal heart function consists of muscle contraction during systole and muscle relaxation during diastole. Diastolic dysfunction refers to a condition in which abnormalities in mechanical function are present during diastole, namely impaired relaxation and increased stiffness. Both systolic dysfunction and diastolic dysfunction will ultimately lead to heart failure. We are specifically interested in diastolic heart failure, because the prevalence continues to rise and there is no effective therapy for this condition till today. The diagnosis of diastolic heart failure is based on echocardiographic evidence of diastolic dysfunction - signs of increased muscle stiffness and reduced relaxation. There are a number of risk factors that are believed to contribute to the development of diastoic dysfunction, including high blood pressure, diabetes and overweight. More importantly, an effective treatment of the risk factor may reverse the diastolic dysfunction. However, when diastolic heart failure is present, none of the treatment has shown the benefit. This highlights the importance of early detection and early intervention in the prevention of diastolic heart failure, by recognizing the risk factors. Therefore, the goal of this study is to identify the risk factors associated with diastolic dysfunction, by reviewing the existing chart and echocardiographic data.
IRB No. 18-148-2 (Dr. Kai Chen, PI): Sleep Apnea and Diastolic Dysfunction (SADD) Study
Obstructive sleep apnea (OSA) is strongly associated with a number of cardiovascular diseases including hypertension, atrial fibrillation, coronary artery disease, and heart failure. Hypothesis: Obstructive sleep apnea is linked to diastolic heart failure as evident by echocardiographic evidence of diastolic dysfunction. Aims of this study are (1) to determine whether OSA is associated with diastolic dysfunction by comparing the echocardiographic parameters between the subjects with abnormal sleep study and those with normal sleep study;(2) to determine if the severity of OSA as evaulated by the sleep study is associated with the degree of diastolic dysfunction; (3) to determine whether left atrial strain imaging as a part of diastolic dysfunction parameters closely correlates to the severity of OSA.
IRB No. 18-154-2 (Dr. Kai Chen, PI): Left Atrial Mechanical Function and Atrial Fibrillation (LameAfib Study)
Atrial fibrillation (Afib) is the most common cardiac arrhythmias encountered in clinical practice. Afib worsens quality of life with symptoms of dyspnea, palpitation, and fatigue; and contributes to an increased risk of thromboembolic stroke and mortality. As arhythm-control strategies, direct-current cardioversion (DCCV) and catheter ablation are two therapies to restore sinus rhythm.The recurrence of Afib after DCCV or catheter ablation remains a major problem. For example, the Afib recurrence rate reached 30% at 3 months and 60% at 12 months after DCCV. A reliable prediction of the Afib recurrence will help guide the treatment strategy. Previous report has shown that left atrium (LA) size is a strong independent predictor of Afib recurrence after catheter ablation. Another report demonstrated echocardiographic diastology variables such as mitral annular velocity (e wave) and septal E/e ratio, but not LA dimensions, are the best predictors of recurrence after DCCV. Therefore, the goal of this study is to evaluate echocardiographic variables related to left atrial remodeling by strain imaging as a tool to predict atrial fibrillation recurrence after cardioversion or ablation. This is a retrospective chart review study to evaluate the echocardiographic findings in relation to Afib recurrence in the patients with Afib who underwent cardioversion or catheter ablation between 01/01/2013 and 12/31/2017.
IRB No. 11-009-3.2 (Dr. Molly Brewer, PI): GOG 212 A Randomized Phase III of Maintenance Chemotherapy Comparing 12 Monthly Cycles of Single Agent Paclitaxel or CT-2103 VS No Treatment Until Documented Relapse in Women with Advanced Ovarian, Primary Peritoneal or Fallopian Tube Cancer Who Achieve a Complete Clinical Response to Primary Platinum/Taxane Chemotherapy
Study description not available
IRB No. 12-013S-3.2 (Dr. Biree Andemariam, PI): Biomechanical Properties of Blood Cells in Sickle Cell Disease
Study description not available
IRB No. 18-104-1 (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 (Dr. Agnes Kim, PI): Assessment of Cardiac Abnormalities in Sickle Cell Patients Using Echocardiography
Assessment of Cardiac Abnormalities in Sickle Cell Patients Using Echocardiography
IRB No. 18-000-3.2 (Dr. Michael Michonski, PI): Antibiotic Regimens in Patients Undergoing Tumor Resections with Endoprosthetic Replacements.
This study is a multi-center, blinded, randomized controlled trial, using a parallel two-arm design to investigate whether long term postoperative antibiotic regimens (5 days) will decrease the rate of infection among patients being surgically treated for a lower extremity bone tumor, when compared to short term postoperative antibiotics (24 hours). We will assess infection rates within 12 months after initial surgery across both study arms. We will measure function and quality of life preoperatively, and at 3 months, 6 months, and 1 year postoperatively.
IRB No. 10-068SJ-3.2 (Dr. Ethan Bortniker, PI): Identifying Early Clinical and Molecular Markers of Colon Cancer Risks
Study description not available
IRB No. 17-014-3.2 (Dr. Robert Arciero, PI): Mid- and Long-Term Outcomes for Patients Treated with High Tibial Osteotomy
We would like to know more about the outcomes of patients who underwent an arthroscopic high tibial osteotomy (a.k.a. realignment of the knee by cutting the tibia). To better understand the outcomes of this treatment, we are conducting a research study and inviting participation from all patients treated by Dr. Robert A. Arciero who underwent an HTO at least two years ago. This is a case series study with three distinct parts: (1) a limited retrospective chart review, (2) a prospective survey and detailed retrospective chart review for responders, and (3) a detailed retrospective chart review for non-responders. The purpose of the limited retrospective chart review is to collect the minimum information necessary to determine eligibility and to contact eligible patients. Then, eligible patients will be contacted to invite participation in the prospective survey and detailed retrospective chart review. For patients who respond, the survey is used to collect postoperative outcome information regarding current pain, satisfaction and functional outcomes. Patients who respond will also be included in a detailed retrospective chart review to collect information regarding demographics, preoperative clinical factors, radiographs and the HTO procedure in order to examine relationships between preoperative and operative findings as well as the postoperative outcomes collected during the prospective survey. Patients who do not respond by enrollment closure will be considered lost to follow-up. A second detailed retrospective chart review will be performed to include these non-responders in order to adequeately characterize the study population and to determine whether there are differences in the distribution of clinical or demographic variables.
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. 18-175-1 (Dr. Santhanam Lakshminarayanan, PI): A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study to Evaluate Efficacy and Safety of BMS-986165 in Subjects with Systemic Lupus Erythematosus
The purpose of this research study is to measure how well and how safe BMS-986165 is in treating patients with Systemic Lupus Erythematosus (SLE) and to determine the optimal dose level. This will be done by measurements on how subjects are feeling, any side effects or changes to subject's laboratory tests. Animal and human studies have shown that BMS-986165 may help control the activity of cells in the immune system that may be responsible for the signs and symptoms of SLE as well as treating the signs and symptoms of other autoimmune and inflammatory diseases such as psoriasis.
IRB No. 18-201C-1 (Dr. Damion Grasso, PI): Adaptation and Resilience in Childhood Study R01
In the current application we propose applying advances in developmental measurement science, including those developed in our own lab, towards sensitive characterization of interpersonal violence (IV) exposure, biobehavioral indicators of threat detection and reactivity, trauma-related psychopathology, and contextual risk and protective factors in a high-risk sample of preschool age children. Assessment will include (1) the Family Socialization Interview-Modified (FSI-M), a comprehensive interview measuring children's experiences from birth to present, including family stressors, parenting practices and family conflict that was developed in our lab, (2) the Anxiety Dimensional Observation System (ANX-DOS) and (3) the Disruptive Behavior Dimensional Observation System (DB-DOS), two laboratory observation paradigms for characterizing fear/anxiety and anger/affect regulation, respectively, also developed in our lab, (3) a multiple source assessment of trauma exposure and trauma-related symptoms as defined by the DSM-5, (4) attention bias, autonomic (heart rate, skin conductance), and electrophysiological (Event-related potentials) responses to laboratory-based threat stimuli, and (5) observed and reported maternal sensitivity and parent-child interaction. In the current project, families will be recruited from domestic violence shelters and communities surrounding the shelters. Some families will have experienced IV and others will not. Research visits will occur at our child-friendly laboratory on the UConn Kane Street property in West Hartford and will last approximately four hours. Families will be compensated for their time. Specific Aims: Specific Aim 1. To demonstrate that how children respond to negative (threat) stimuli presented in the laboratory is related to their symptoms of fear and distress. Specific Aim 2. To test the hypothesis that how children respond to threat stimuli is the link between their exposure to interpersonal violence and the development of symptoms of fear and distress. Specific Aim 3. To test the hypothesis that mothers' responsiveness to their children will shape children's threat reactivity and the development of symptoms over time.
IRB No. 19-006-2 (Dr. Mohamad Halawi, PI): Comparison of home health services versus surgeon-directed home rehabilitation following total joint arthroplasty: a randomized controlled trial.
There is limited prospective research examining clinical outcomes in joint replacement surgery for patients receiving an unsupervised home rehabilitation program. Recent literature suggests that patients experience the same clinical outcomeswhen they perform physical therapy independently at home following a surgeon's direction (surgeon-directed home rehabilitation)compared to their receiving visiting physical therapists at their home (home health services). There is also a dramatic cost benefit from prescribing unsupervised physical therapy. Hypothesis: Surgeon-directed home rehabilitation is clinically non-inferior to home health services while being significantly less costly. Objectives: To assess clinical outcomes, complications, and cost-effectiveness of surgeon-directed home rehabilitation compared with home health services.
IRB No. 08-088-3.2 (Dr. Rajesh Lalla, PI): Anti-Inflammatory Intervention in Radiation-induced Oral Mucositis
Study description not available
IRB No. 18-228-2 (Dr. Agnes Kim, PI): Assessment of Myocardial Deformation in Adult Patients with Type 2 Diabetes Mellitus
This retrospective case-control study aims to determine if patients with early-stage diabetic cardiomyopathy have subtle myocardial deformation usingspeckletracking echocardiogram. The two aims of the study are (1)to determine whether adult diabetic patients with preserved left ventricular ejection fraction have abnormalities in myocardial deformation and (2) to determine whether adult diabetic patients have impaired diastolic function as assessed by traditional methods as well as by novel method, i.e. left atrial strain, a measurement that has been shown to correlate with pulmonary capillary wedge pressure.