Clinical Research Directory

Vascular Disease Discovery Protocol

Background: Some genetic diseases put increase the risk of heart and blood diseases, which are the number one cause of death and disability in the U.S. Researchers want to study diseases of the heart and/or blood vessels. They want to collect data and specimens from affected people, their family members, and healthy people. Objective: To study diseases of the heart and/or blood vessels. Eligibility: People age 2 and older who may have genetic disease affecting the heart and/or blood vessels Their relatives Healthy volunteers Design: Participants will be screened with a medical history, physical exams, and imaging tests. Participants may have a few visits or visits for 2 weeks or more. This will depend on their age and disease status. Visits may include: Photographs of the face and body Heart tests Samples taken of blood, urine, saliva, skin, and/or tissue Scans. For some, a dye may be injected into a vein. A six-minute walk test Lung tests. For some, participants will blow into a tube. For others, they will breathe in a gas from a mask, have a small injection, then have a scan. Stress tests while walking on a treadmill or riding a stationary bike Ultrasound of veins and arteries Devices outside the body testing the stiffness and function of arteries Eye exam and eye tests. For some, a dye may be injected in a vein. Blood pressure tests Measurements of blood flow under the skin and in the arms and fingernail blood vessels Devices outside the body testing flexibility of the blood vessels and skin, and skin temperature

Outcomes of Health Care Transition for AYA With a Cancer Predisposition

This observational study evaluates whether adolescents and young adults (AYAs) with a cancer predisposition syndrome (CPS) establish and maintain adult health care and continue CPS-specific cancer surveillance after graduating from pediatric care at St. Jude Children's Research Hospital (SJCRH). Participants will complete a Readiness Assessment and periodic surveys over 8 years post-graduation. Primary Objectives * To evaluate whether adolescents and young adults (AYAs) with a cancer predisposition syndrome (CPS) report they have established care with adult health care providers and pursue CPS-specific cancer surveillance within 1-year post-graduation from SJCRH. * To evaluate whether AYAs with CPS report they maintain care with adult health care providers and continue CPS-specific cancer surveillance 3 years post-graduation from SJCRH. Exploratory Objectives: * To evaluate whether AYAs with CPS report they continue to maintain care with adult health care providers and complete CPS-specific cancer surveillance longitudinally 5 years and 8 years post-graduation from St. Jude Children's Research Hospital (SJCRH). * To examine clinical correlates of establishing care with adult providers and initiating CPS-specific cancer surveillance post-graduation from SJCRH. * To identify the tumors diagnosed in AYAs with CPS after they graduate from SJCRH and determine how these tumors were identified (i.e., through specific surveillance tests or based on symptoms). * To identify barriers and facilitators AYAs face when establishing and maintaining adult health care and pursuing CPS-specific cancer surveillance.

Care Plans for Cancer Predisposition

Develop and evaluate acceptability, feasibility, and preliminary efficacy of digital care plan and accompanying text message reminders for children and adolescents with a known Cancer Predisposition Syndromes (CPS).

COsegregation of VARiants in Panel of Genes

The aim of the COVAR project is to achieve reliable classification of as many variants of interest as possible from the French OncoGenetics Database (FrOG, https://frog-db.fr/) in order to use them for the genetic counseling. The results obtained through this study will have a major impact on clinical management of the patients and their families conducting in some cases to propose a prophylactic surgery.

The Preventive Risk Outreach And Cascade Testing

The goal of this clinical trial is to learn whether a new online program developed by the research team is able to help families learn about family cancer risk and how to reduce this risk, as well as help interested family members get low-cost, at-home genetic testing for cancer risk.

Diagnostic Value of Exome/ Genome Sequencing, Conventional Methods in Rare Diseases and Familial Tumor Syndromes

For the retrospective data analysis, patients with genetic diseases of any age and, if available, other family members, for whom genetic analyzes were carried out between 10/2016 and 12/2020, should be included. This equates to approximately 13,000 records, minus combined analyzes in the same patient, an estimated 12,000 individuals.

Enhancing Information Management for Young Adults After Genetic Cancer Risk Testing

This research is being done to develop the electronic platform Nest for young adults (ages 18-39) who have had prior cancer genetic testing. The platform will give patients and their clinicians access to continuously updated information about both pathogenic variants and variants of uncertain significance (VUS). The name of the intervention used in this research study is: Nest portal (electronic platform for patients and clinicians)

Pre Pectoral Implant for Immediate Breast Reconstruction Using Single Port Endoscopy in Prophylactic Indication

Implant-based reconstruction is currently the most common choice for mastectomy reconstruction. Whatever the choice of mastectomy incision, a scar remains on or near the breast volume. Current techniques involve partial or total coverage of the implant with the pectoralis major muscle, to prevent exposure or infection. The muscle dissection technique applied has functional and cosmetic consequences. In this study, an endoscopic approach will be evaluated. This new surgical technique, using a single-port endoscopic way, will put the scar is in the axillary area, away from the breast. The hypothesis is that this delocalized scar potentially reduces the risk of exposure and allows placement of the implant in the subcutaneous space, with no manipulation of the pectoralis major muscle.

Barriers and Facilitators of Parent-Child Communication in Children With Cancer Predisposition

Testing children, adolescents, and young adults (CAYA) for a genetic risk for cancer can help with early prevention and detection of cancers through regular follow-ups and medical care. After receiving genetic test results, CAYA may not accurately understand what their results mean, and parents are often unsure about talking with their CAYA about their genetic risk for cancer. By understanding how parents communicate with their CAYA, the investigators can improve future genetic education to reduce cancer risk. Primary Objectives: * Identify qualities of parent-CAYA (child, adolescent, and young adults) communication about CAYAs' genomic cancer risk, and their association with CAYAs' psychosocial and prevention outcomes. * Examine the association between sociodemographic, cancer-related, and psychosocial factors and parent-CAYA communication regarding CAYAs' genomic risk for cancer. * Identify barriers and facilitators of parent-CAYA communication regarding CAYAs' genomic risk for cancer.

Pancreatic Cancer Early Detection Consortium

The purpose of the Pancreatic Cancer Early Detection (PRECEDE) Consortium is to conduct research on multiple aspects of early detection and prevention of pancreatic ductal adenocarcinoma (PDAC) by establishing a multisite cohort of individuals with family history of PDAC and/or individuals carrying pathogenic/likely pathogenic germline variants (PGVs) in genes linked to PDAC risk for longitudinal follow up.

GLUCOSE-MGH: Genetic Links Understood Through Challenge With Oral Semaglutide Exposure at MGH

The goal of this research study is to evaluate the pathophysiologic mechanisms by which genetic variation impacts response to an FDA-approved medication commonly used to treat type 2 diabetes called oral semaglutide (Rybelsus) and to characterize the physiological response to a mixed meal tolerance test (MMTT) before and after a 14-day treatment with oral semaglutide. The investigators will do this by measuring factors in the blood, such as sugars, fats, metabolites, and proteins, after eating a standardized breakfast meal at the first visit and after taking 14 doses of oral semaglutide over two weeks before the second study visit. The food (mixed meal breakfast) we will be studying is specially prepared to contain a set amount of protein, carbohydrates, and fat. The investigators hypothesize that understanding how the acute biochemical response to oral semaglutide differs by genetic variation will generate insight into drug mechanisms and type 2 diabetes pathophysiology.

Assessment of Topical Minoxidil on Intraoperative Flap Perfusion and Cutaneous Flap Viability in Breast Recon

The purpose of the study is to determine whether pharmacologic delay using minoxidil in patients undergoing bilateral risk reducing mastectomy with reconstruction could achieve improvement in flap perfusion and flap viability at the time of surgery. Patients will undergo randomization of their breasts to determine which breast will receive the experimental intervention and which breast will serve as the internal control (receive placebo). The experimental breast will receive the novel pharmacologic delay treatment, 5% minoxidil, while the internal control breast will receive the current standard of care, which does not include any topical application prior to surgery - a placebo control will be used. This will be a triple-blind study, where both the participants and investigators will be blinded to which breast will receive the intervention. The patients will receive two bottles "compound A" and "compound B" with directions from the pharmacy for which compound to apply to each breast. Product will be applied for 2 weeks prior to planned surgery. Surgery will proceed without any changes to standard practice.

Prospective Multicenter Registry of Gender, Diversity and Inclusion (GEDI) of Women With Acute Coronary Syndrome

Create a multicenter prospective registry that collects information from women affected by acute coronary syndrome (ACS). This registry aims to understand the diversity in the presentation of women with ACS. It proposes to conduct a thorough characterization of the women involved in the study through genetic, biochemical, and molecular analysis.This approach aims to identify any differences in the characteristics of women with ACS and to identify disease subtypes that may influence treatment options and clinical outcomes.

EXOME Analysis Position in the Strategy of Genetic Predisposition Factors Identification in Early-onset Cancer

5 to 10% of cancers are due to the presence of a constitutional genetic alteration. It can be inherited from parents (family form) or by accident, in the first moments of life after fertilization (sporadic form). In both cases, this genetic alteration is constitutional and transmissible to descendants. It is hereditary. When an hereditary early form is suspected, several well-known genes generally involved in genetic predispositions to cancer are found by a technique called " gene panel ". However, this analysis does not always identify the genetic predisposing factors for cancer. New techniques called "high-throughput exome sequencing (SHD-E)", allow more than the analysis of the the gene panel. These analysis allow to identify alterations in other genes that could contribute to the development of cancer. The objective of the Ex²trican study is to show, from patients with early cancer (sporadic or familial form), that this approach to exome sequencing can be effective to identify new genetic risk of cancer, when the first panel analysis of genes is negative.

Mayo Clinic Precure - Prospective Study

The goal of this observational study is to 1) better understand and predict biological processes before disease begins or is identified, 2) study genomic and environmental contributors to disease, 3) identify ways to stop disease advancement before it becomes serious or complex, and 4) identify potential targets for disease therapy. Participants will be asked to: * collect biological samples, * download a mobile app, * collect speech (voice) recordings, and * complete surveys

Growing Up in Singapore Towards Healthy Outcomes

This study aims to examine the role of genetic and epigenetic factors, maternal nutrition, lifestyle, emotional health, and other environmental factors in pregnancy or postpartum period that can influence future maternal risk of metabolic and mental wellness, including body weight changes. The study will recruit women in early pregnancy and later follow their children after birth, tracking both the mother and child until the child reaches at least 20 years of age.

The Effect of rs7903146 Genotype on Islet GLP-1 Production in Humans

The investigators recently demonstrated that blockade of Glucagon-Like Peptide-1's (GLP-1) receptor (GLP1R) results in changes in islet function without changes in circulating GLP-1. These effects are more pronounced in people with early type 2 diabetes (T2DM) in keeping with increased expression of PC-1/3 and GLP-1 that is observed in diabetic islets. However, its regulation is at present unknown. Common genetic variation in the TCF7L2 locus (T-allele at rs7903146) arguably confers the greatest genetic risk of T2DM. It is associated with α- and β-cell dysfunction. TCF7L2 (the product of TCF7L2) was first described as the transcription factor necessary for proglucagon expression in intestinal L-cells (which secrete GLP-1). This led to speculation that TCF7L2 confers risk of diabetes via changes in circulating GLP-1. This has turned out to not be the case. This raises the possibility that these diabetogenic effects are mediated via an inability of islet GLP-1 to adapt to rising glycemia. Therefore, this experiment will determine the contribution of islet GLP-1 to the functional abnormalities of the islet associated with the TCF7L2 locus.

Genetic Investigation of Cancer Predisposition

Clinical information and samples (blood, saliva, and tumor) will be collected from patients with multiple cancers and/or a family history of cancer as well as from affected and unaffected relatives; samples will be systematically sequenced and evaluated for candidate driver mutations.

Precision Medicine in the Prostate Cancer Care Pathway

This study aims to evaluate the use of a prostate cancer specific predisposition genetic panel test in men with / at high risk of prostate cancer. The genetic test will analyse men's DNA samples for the presence of mutations in rare genes as well as common genetic variation to provide men with information about their risk of prostate cancer. This study will evaluate the clinical impact of the test on risk assessment and clinical management in terms of screening and treatment.

Understanding Gene ENvironment Interaction in ALcohol-related Hepatocellular Carcinoma

It has been estimated that alcohol causes around 40% of premature liver deaths in Europe each year, although this number is probably underestimated. Alcohol-related liver disease (ALD) is the most common cause of liver cirrhosis and liver death in Europe with a peak age of deaths occurring among individuals aged 40 to 50. Despite these findings, ALD is little studied with only 5% of all clinical trials in the field of liver disease recorded on ClinicalTrials.gov and only 5% of all publications in the same research area. Liver cancer is the second most common cause of cancer-related death (15-20% survival at 5 years) and the second most common cause of alcohol-related cancers worldwide. Like other complex diseases, ALD-HCC results from the interaction between environmental determinants and genetic variations but knowledge of gene-environment interactions is currently lacking in this area. The GENIAL project will address these needs through a comprehensive evaluation of gene-environment interactions concerning ALD-HCC.

PTX3-targeted Antifungal Prophylaxis

This is a prospective genetically-stratified randomized double-blind event-driven multicentre clinical trial to assess the efficacy of posaconazole-based antifungal prophylaxis allocation strategies for patients with acute myeloid leukemia who receive induction chemotherapy. Allocation strategy based on an invasive mold infection genetic risk will be double-blinded.

Evaluation of Risk of hEpatocellular Carcinoma

Hepatocellular carcinoma (HCC) is the fifth most common solid cancer and the second cause of cancer-related mortality worldwide. Nonalcoholic fatty liver disease (NAFLD), that is hepatic accumulation of fat in excess of 5% not explained by at risk alcohol intake, is projected to become the leading cause of HCC in Western countries within 2025.NAFLD is most frequently caused by insulin resistance due to unhealthy lifestyle. Due to the epidemics of obesity and type 2 diabetes, NAFLD now affects one in three individuals worldwide. NAFLD-HCC frequently develops without overt cirrhosis suggesting that steatosis directly promotes hepatic carcinogenesis.

Prostate Tissue BioBank

Prostate cancer is also the most common cancer in men with inherited pathogenic variants in BRCA1 and BRCA2. Beyond BRCA1/2, other genes are known to increase the risk of prostate cancer, including ATM, TP53 and HOXB13. The investigators have shown that 5% of men diagnosed with prostate cancer localized to their prostate gland and up to 10-15% of patients with metastatic prostate cancer gland are carriers of an inherited gene mutation. The Prostate Tissue BioBank is a prospective study which aims to create a biorepository of prostate tissue samples from prostate biopsies and prostatectomies and matched germline DNA from pathogenic mutation carriers in addition to age-matched control samples. Our primary goal is to investigate prostate cancer development and treatment response in carriers of germline DNA repair mutations, as compared to non-carrier controls.

Mayo Clinic Tapestry 2.0: Applying Multi-Omics for Scientific Discovery

The purpose of this study is to use multi-omics testing on samples collected from Mayo Clinic patients to build and expand on what has been learned about genomic data.