Several studies have reported that diabetic subjects have lower plasma vitamin C concentrations than non-diabetic subjects. Although urinary vitamin C loss in diabetic subjects was reported to be increased in two studies, these are difficult to interpret due to lack of controlled vitamin C intake, inadequate sampling, lack of control subjects, or methodology uncertainties in vitamin C assay and sample processing. Consequently, it is unclear whether diabetic subjects truly have both low plasma and high urine vitamin C concentrations. We propose that low plasma vitamin C concentrations in diabetic subjects are due in part to inappropriate renal loss of vitamin C in these subjects but not in healthy controls. We will study nondiabetic controls and cohorts with diabetes. Vitamin C concentrations in plasma, RBCs, and urine will be measured in outpatients. In those willing to be admitted to the Clinical Center, we will measure vitamin C pharmacokinetics to determine the relative bioavailability for vitamin C in individuals with and without abnormal urinary loss of vitamin C (or renal leak). Single nucleotide polymorphisms (SNPs) will be determined in genomic DNA responsible for the two proteins mediating sodium dependent vitamin C transport, SVCT1 and SVCT2. We will also explore mechanisms underlying abnormal urinary vitamin C loss.

Type: Observational

Start Date: Apr 2006

open study

Background: Negative emotional states can affect a person s behavior as they make decisions. For example, hunger may make people more impatient; they may then make riskier choices. Other negative emotional states that can change behavior include stress, pain, and sadness. By learning more about how emotions affect thinking and behavior in healthy people, researchers hope to better understand how to identify and treat people with mental disorders. Objective: To learn how negative emotions affect the brain and decision-making behavior. Eligibility: Healthy people aged 18 to 55 years. Design: Participants will have 3 clinic visits in 3 weeks. Participants will fill out questionnaires. They will be asked about their personal history, their personality, and state of mind. For 2 visits, participants will be assigned to different groups. Each group will experience 1 type of emotional stressor: Some participants will watch a video. Some will have to do arithmetic problems. Some will have heat applied to an arm or leg. Some will experience cold by immersing their hand in ice water. For a snack craving test, some will be tempted by food after a 4-hour fast. During these tests, participants will have sensors attached to their bodies. They will be videotaped. Saliva samples will be collected. After the stressors, participants will do tasks on a computer. They will need to make choices. Some participants will perform these decision-making tasks while lying in a brain scanner for functional magnetic resonance imaging. The brain scan involves lying on a table that slides into a cylinder that takes images of the brain. ...

Type: Interventional

Start Date: Jul 2023

open study

Magnetic Resonance Imaging (MRI) unlike X-rays and CT-scans does not use radiation to create a picture. MRI use as the name implies, magnetism to create pictures with excellent anatomical resolution. Functional MRIs are diagnostic tests that allow doctors to not only view anatomy, but physiology and function. It is for these reasons that MRIs are excellent methods for studying the brain. In this study, researchers will use MRI to assess brain anatomy and function in X and Y chromosome variation, healthy volunteers, and patients with a variety of childhood onset psychiatric disorders. The disorders include attention deficit disorder, autism, congenital adrenal hyperplasia, childhood-onset schizophrenia, dyslexia, obsessive compulsive disorder, Sydenham's chorea, and Tourette's syndrome. Results of the MRIs showing the anatomy of the brain and brain function will be compared across age, sex (gender), and diagnostic groups. Correlations between brain and behavioral measures will be examined for normal and clinical populations....

Type: Observational

Start Date: Jun 1990

open study

Obesity is a major risk factor for hypertensive disorders of pregnancy (HDP). The underlying mechanisms are largely unclear, but maternal vascular endothelial dysfunction is likely involved. Endothelial dysfunction in HDP could be attributed to 1) alterations in the L-arginine/nitric oxide (NO) pathway, and 2) an increase in endothelin-1 (ET-1). Additionally, augmented sympathetic vasoconstriction may also contribute to HDP. Chronic (repeated) whole-body heat exposure has been shown to increase NO bioavailability, decrease ET-1, and cause functional and structural adaptations in the vasculature. All these can improve vascular function, attenuate sympathetic (re)activity, lower blood pressure (BP), and reduce cardiovascular risk in non-pregnant individuals. Whether this is also true after regional (leg) heating in high-risk pregnant women is unknown. The investigators' central hypothesis is that chronic leg heating will be effective in improving vascular endothelial function and attenuating sympathetic vasoconstriction, leading to a reduction of the risk for HDP in pregnant women with obesity. The overarching goal of this proposal is to determine the vascular and neural effects of chronic leg heating in obese pregnancy. The study team plans to enroll pregnant women with obesity between 12-14 weeks of gestation and randomly assign them to either an intervention group or a control group (1:1 ratio). Participants in the intervention group will perform 16 weeks of home-based leg heating using a portable sauna blanket up to the hip (temperature of the blanket will be set at 65°C, 4 times/week, 45 min/session), whereas women in the control group will set the temperature of the blanket at 35°C at the same frequency and duration. Participants will be evaluated at baseline and then at 28-30 weeks of gestation. Aim 1 will determine the effects of chronic leg heating on maternal vascular function and surrogate markers of HDP. Aim 2 will determine the effects of chronic leg heating on sympathetic vasoconstriction and BP. Findings from this project will provide insight on the extent and potential mechanisms of how chronic leg heating works for improving vascular endothelial function and sympathetic vasoconstriction in pregnant women with obesity. Results obtained will set a foundation for future large multicenter clinical trials to determine the efficacy and generalizability of home-based leg heat therapy as a safe, ease-of-use, cost-effective, and non-drug approach for reducing the risk of HDP.

Type: Interventional

Start Date: May 2025

open study

Extracellular vesicles (EVs) play a role in obesity-induced insulin resistance and likely impact the development of cardiovascular disease. However, little is known on how EVs affect vascular insulin action in people. The purpose of this study is to understand how EVs play a role in type 2 diabetes related cardiovascular disease. This research will also study if exercise can change how EVs impact blood flow and metabolic health. This study will contribute to designing precision medicine to treat/prevent cardiovascular disease in type 2 diabetes.

Type: Interventional

Start Date: Feb 2025

open study

A Prospective, Multicenter, Randomized, Pivotal Study of the May Health System in Transvaginal Ablation of Ovarian Tissue under Ultrasound Guidance in Women with Infertility due to Polycystic Ovary Syndrome

Type: Interventional

Start Date: Mar 2024

open study

The purpose of this study is to develop and test two brief online writing interventions to improve parental acceptance of sexual and gender minority youth (SGMY) in the Southeast United States.

Type: Interventional

Start Date: Nov 2023

open study

This project proposes to use telemedicine-delivered cognitive-behavioral therapy (CBT) enhanced with continuous glucose monitor (CGM) review to target diabetes distress in adults with type 1 diabetes. The efficacy of CBT for diabetes distress (CBT-DD) will be tested in comparison to commercial FDA-approved CGM only in a randomized controlled clinical trial. The investigators' central hypothesis is that the addition of a CBT intervention that targets diabetes distress and self-management directly will yield clinically significant improvements in both diabetes distress and glycemic control relative to CGM alone. The investigators propose to recruit 93 adults (age 18-64) with type 1 diabetes from a national population for an entirely virtual 6-month study over four years, with targeted recruitment of racial/ethnic minorities. In addition to standard measurement of HbA1c for glycemic control and validated patient-reported outcome (PRO) surveys, the investigators plan to innovatively integrate momentary psychological and behavioral data via smartphone-based ecological momentary assessment with CGM data to assess day-to-day changes in diabetes distress, affect, self-management, and glycemia over the course of the trial.

Type: Interventional

Start Date: Jun 2022

open study

This study will compare the effects on cardiorespiratory fitness (CRF) of aerobic exercise in different amounts (number of minutes/session) over different periods of time (number of weeks). Aerobic exercise is physical activity of light-to-moderate intensity that uses the large muscle groups (muscles in your legs, buttocks, back, and chest) and can be performed for at least 10 minutes. The researchers will study the effects of different exercise programs on how well the study participants' bodies use oxygen, how well their heart pumps blood, how well their lungs function, and how healthy their blood vessels are.

Type: Interventional

Start Date: Oct 2020

open study

The purpose of this study is to develop and evaluate the usefulness of MRI using 129Xe gas for regional assessment of pulmonary function. Specifically, three forms of 129Xe MRI contrast will be the investigators focus - 1) imaging of the 129Xe ventilation distribution, 2) imaging the alveolar microstructure via the 129Xe apparent diffusion coefficient (ADC), and 3) imaging 129Xe that dissolves in the pulmonary blood and tissues upon inhalation. Such imaging of 129Xe gas transfer is expected to be uniquely sensitive to pathologies affecting gas exchange (fibrosis, emphysema, pulmonary hypertension) and provide new insights regarding the normal resting heterogeneity of pulmonary gas exchange.

Type: Interventional

Start Date: Jan 2011

open study

Background: - Atopic dermatitis, or eczema, is a chronic skin disorder. Patients sometimes have infections with S. aureus bacteria. Researchers want to study how eczema treatments affect the number and the type of bacteria on the skin. Objectives: - To study the effect of eczema treatments on skin bacteria. Eligibility: - Individuals between 2 and 25 years of age who have moderate to severe atopic dermatitis. - Healthy volunteers between 18 and 40 years of age with no history of eczema. Design: - Participants will be screened with a physical exam and medical history. Research samples will be collected. Skin biopsies may also be performed. - All participants will be assigned to one of several study groups. - Healthy volunteers must not have taken antibiotics in the year before the start of the study. - All participants will have regular study visits during their 1-year participation. More research samples will be collected at these visits. - Healthy volunteers may be asked to come in for a one-time follow up after the 1 year mark.

Type: Interventional

Start Date: Sep 2012

open study

Background: Shingles is a painful, blistering rash caused by the same virus that causes chickenpox. Shingrix is a vaccine approved to prevent shingles in healthy adults over age 50 and in immunocompromised adults over age 18. Researchers want to learn more about how people with HIV respond to Shingrix. Objective: To learn how Shingrix affects the immune response in people with HIV. Eligibility: People aged 18 years and older with HIV. Healthy people aged 50 years or older are also needed. Design: Participants will have at least 4 clinic visits in 1 year. Participants will be screened. They will have a physical exam with blood and urine tests. At their first visit, participants will receive Shingrix as a shot in the upper arm. They will have a rectal swab; a cotton swab will be inserted into the rectum and rotated gently to collect bacteria. Participants will receive a second shot of Shingrix 2 months after the first one. They will visit the clinic again 3 and 12 months after the first shot. Participants will receive a 28-day memory tool. They will write down their symptoms between clinic visits. They will have up to 4 phone calls to talk about side effects of the shot. Participants may undergo apheresis: They will lie still while blood is drawn from a needle in one arm. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be given back through a second needle in their other arm.

Type: Interventional

Start Date: Mar 2023

open study

This study will examine the safety of giving the experimental drug, resiniferatoxin (RTX), to treat severe pain in patients with advanced cancer. RTX is a chemical extracted from a cactus-like plant. It is similar to capsaicin, the active ingredient in hot pepper. RTX has relieved pain and reduced the need for pain medication in several animal experiments. It works by destroying nerves that transmit pain information. People at least 18 years of age with severe pain from advanced cancer at or below the level of the chest that cannot be controlled with standard treatments may be eligible for this study. Participants undergo the following procedures: Pretreatment Visit Before beginning treatment with RTX, patients give a medical history and undergo a physical examination that includes: - Electrocardiogram (EKG) - Blood draw - Urinalysis - Neurological examinations - Peak expiratory flow rate (PEFR) - Eye examination - MRI - Urology assessment - Pregnancy test, when appropriate - Questionnaires to collect information on health, personality, mood, pain levels and symptoms. 2-Day Hospitalization Patients are hospitalized for 2 days for RTX injection and monitoring, as follows: - RTX injection: RTX is injected in the operating room under general anesthesia. It is given through a catheter placed in the patient s spine. The catheter is also used to obtain samples of cerebrospinal fluid (CSF) the clear fluid that bathes the spinal cord. The fluid is examined to assess drug effects and side effects, chemical changes in the content of the CSF associated with RTX, and how RTX is handled by the body. - Post-injection monitoring, including: - Surveys about symptoms such as pain or weakness - Neurological examinations - Blood and CSF sampling - EKG - AEs Outpatient followup - Vitals - Blood draw, Urinalysis, neurological and sensory testing, EKG on days 7, 14 and 30 after the injection - MRI scans of the head and back, Urology assessment and PEFR on day 15 after the injection - Eye examination - Follow-up phone calls monthly for 6 months

Type: Interventional

Start Date: Aug 2009

open study

Background: Researchers use mixed meal tolerance tests (MMTTs) to look at how people s bodies respond to eating a meal. However, researchers do not agree on how to decide the number of calories to give in each meal. Some use fixed meals, which are the same size for everyone, and some use adjusted meals, based on the size of the person s body. Researchers want to know which MMTT is best to use for future research. Objective: To learn how fixed vs adjusted meals affect blood glucose levels in healthy people. Eligibility: Healthy people aged 18 years or older. Design: Participants will have 3 or 4 clinic visits of up to 8 hours in 8 weeks. Participants will have baseline tests: Their height, weight, and waist size will be measured. They will have an oral glucose tolerance test: A needle attached to a tube (IV) will be inserted into a vein in the arm. They will have a sugary drink. Blood samples will be taken from the tube at intervals up to 3 hours after the drink. They will have a body scan. Participants will have 2 MMTT visits. One will include a fixed meal and one will include an adjusted meal. They will have tests at both visits: Resting metabolic rate: A clear hood will be placed over the participant s head while they rest for 20 minutes. This will measure the oxygen they breathe in and out. MMTT. Participants will have 5 minutes to drink a liquid meal. Blood samples will be taken at intervals for the next 4 hours....

Type: Interventional

Start Date: Aug 2024

open study

Background: DNA is a structure in the body. It contains data about how the body develops and works. Telomeres are found on the end of chromosomes in DNA. Some people with short telomeres or other gene changes can develop diseases of the bone marrow, lung, and liver. Researchers want to see if low doses of the hormone drug danazol can help. Objective: To study the safety and effect of low dose danazol. Eligibility: People ages 3 and older with a telomere disease who have either very short telomeres and a specific gene change. They must also show signs of aplastic anemia, lung, or liver disease. Design: Participants will be screened in another protocol. Participants will have: - Medical history - Physical exam - Blood tests - Lung exam. They will breathe into an instrument that records the amount and rate of air breathed in and out over a period of time. 6-minute walking test. - Abdominal ultrasound and liver scan. These tests use sound waves to measure the fibrosis in the liver. Some participants will have: - Pregnancy test - Small sample of the liver removed - Bone marrow biopsy. The bone will be numbed and a small needle will take a sample of the marrow. All participants will have hormone levels checked. All child participants will see a pediatric endocrinologist. Children may need to have a hand x-ray. We will monitor patients for 6 months before starting danazol. Participants will take danazol by mouth twice a day for 1 year. Participants must return to the clinic at 6 months and 12 months while on danazol and 6 months after stopping it. They will have blood and urine tests, a lung exam, abdominal ultrasound, and liver scan.

Type: Interventional

Start Date: Feb 2018

open study

Background: Major depressive disorder (MDD) is a psychiatric condition. People with MDD have occasional bouts of depressive symptoms; these bouts are called major depressive episodes (MDEs). Researchers want to know if people having MDEs have lower levels of an enzyme called PDE4B in their brains. Primary Objective: To determine whether PDE4B is reduced in the brains of individuals with MDD experiencing a major depressive episode (MDE). Secondary Objectives: To determine the optimal length of scanning and the retest variability and reliability of [18F]PF-06445974, and whether PDE4B binding correlates with clinical rating scales. To measure if PDE4B radioligand binding can be blocked by taking apremilast. Eligibility: People aged 18-70 years with MDD. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits. Participants will be screened. They will have a physical exam with blood tests. They will have a test of their heart function. Some participants may have a psychiatric assessment; they will answer questions about their state of mind and related topics. Participants will have magnetic resonance imaging (MRI) of the brain. They will lie on a table that slides into a metal cylinder. Participants will have a positron emission tomography (PET) scan. A needle will be used to guide a thin plastic tube (catheter) into a vein in one arm. An experimental substance called a radioactive tracer ([18F]PF-06445974) will be injected through the catheter. Participants will lie on a table that slides into a doughnut-shaped machine. The scan will last up to 4 hours with a 15-minute break. Participants blood pressure, heart rate, and breathing will be monitored before, during, and after the PET scan. A second catheter will be inserted in the artery of the wrist so blood can be drawn during the scan. Some participants may return for a second PET scan; have a lung scan or receive apremilast. https://nimhcontent.nimh.nih.gov/start/surveys/?s=KE88DXXPLDFHHTF8

Type: Interventional

Start Date: Jun 2023

open study

A Basket Trial of Refractory Rheumatoid Arthritis (RA), Sjögren's Disease (SjD), Idiopathic Inflammatory Myopathies (IIMs) and Systemic Sclerosis (SSc) subjects to evaluate the safety and efficacy of AlloNK, a non-genetically modified allogeneic NK cell, in combination with rituximab.

Type: Interventional

Start Date: Jul 2025

open study

Previous work by the group convinced the researchers to pursue development of focused cognitive reappraisal training as a novel approach to treatment of BPD, either as stand-alone treatment or in concert with evidence-based treatments of BPD. The present proposal aims to refine and test a proposed clinical intervention for BPD patients, training in reappraisal-by-distancing, in terms of its ability to influence hypothesized neural and behavioral targets and, once that is established, to demonstrate its ability improve clinically relevant outcome measures.

Type: Interventional

Start Date: Nov 2024

open study

The goal of this clinical trial is to evaluate if a digital group intervention (named IMAGINE) can prevent depression in perinatal populations. The main questions it aims to answer are: Does IMAGINE engage cognitive behavioral therapy targets? Does IMAGINE lead to lower depression scores? Is IMAGINE acceptable, appropriate, usable and feasible? Participants will be randomized to either participate in an IMAGINE group for 12 weeks or receive standard of care. Participants will respond to questionnaires at enrollment and study visits at 12 and 24 weeks after enrollment.

Type: Interventional

Start Date: Mar 2025

open study

The purpose of this study is to examine how individual differences in interoception (the ability to sense, interpret, and act on bodily feelings like hunger, fullness, thirst, hot, cold, etc.) relate to eating behaviors in children ages 7-10 years. Findings will inform whether interventions targeting interoceptive awareness may be helpful for prevention of obesity and related chronic diseases.

Type: Observational

Start Date: Oct 2024

open study

The goal of this study is to determine how a drug class called glucagon-like peptide-1 receptor agonists (GLP-1Ra) affects people during an early stage of Type 1 Diabetes undergoing clinical teplizumab treatment. This study involves giving participants a liquid meal under different conditions and observing how their bodies respond, focusing on blood sugar levels, insulin effectiveness, and blood vessel function. The meal tests are followed by two post-treatment tests, one with the GLP-1Ra drug and the other with a placebo. Each test involves blood draws before and during the meal test, GLP-1Ra or placebo administration, and an ultrasound to measure blood vessel function. The goal is to see if GLP-1Ra can help manage blood sugar levels and improve cardiovascular health in this population.

Type: Interventional

Start Date: Jun 2024

open study

The 5-year K01 Mentored Research Scientist proposal will employ brain, neurocognitive, and computational tools (e.g., machine learning) to understand the impact of opioid-use disorder (OUD) and common co-occurring issues on executive function and clinical outcomes. There have been record numbers of fatal and non-fatal overdoses (ODs) associated with opioids (and other drugs) in the past 12-months. Improving classification and predictive capabilities to enhance treatment and prevent relapse is of the upmost importance. Deficits in neurocognition often are associated with poor treatment outcomes (e.g., more drug use, medication non-adherence), yet co-occurring issues associated with OUD (e.g., depression, anxiety, physical/sexual abuse, neglect) make it difficult to parse which contributing factors lead to worse executive function (EF) and poorer treatment outcomes. Novel brain, neurocognitive, and computational tools are needed to help determine these differences, in order to lay the foundation for better treatments. This need has shaped both the training plan and the associated research project in a 5-year K01 Mentored Research Scientist proposal, building on Dr. Regier's prior preclinical and clinical addiction neuroscience experience (focused mostly on cocaine-use disorders, cue-reactivity, subcortical networks, prior adversity, and univariate imaging techniques).

Type: Observational

Start Date: Nov 2023

open study

This will be a multi-center, single arm, open-label study of Ovaprene, a non-hormonal intravaginal ring, to investigate the contraceptive effectiveness, safety and acceptability of Ovaprene.

Type: Interventional

Start Date: Dec 2023

open study

Background: About 5 million adults in the U.S. have Alzheimer s disease or another adult-onset neurodegenerative disorder. Many studies have found that inflammation in the brain contributes to these diseases. Researchers want to find a better way to measure this inflammation. Objective: To learn whether COX-1 and/or COX-2 is elevated in the brains of individuals with neurodegenerative brain disease compared to healthy volunteers. Eligibility: Adults age 18 years and older in good general health who have an adult-onset neurodegenerative dementia, such as AD, FTD, corticobasal syndrome, Huntington s disease, or MCI, ALS and healthy adult volunteers enrolled in protocols 01-M-0254 or 17-M-0181. Design: Participants will be screened with medical history, physical exam with vital signs, and lab tests. They will have a neuropsychological testing. Their heart function will be measured. Participants will have a magnetic resonance imaging (MRI) scan. The MRI scanner is a metal tube surrounded by a strong magnetic field. Participants will lie on a table that slides in and out of the tube. The machine makes noise. Participants will get earplugs. Participants will have 2 PET scans. They will be injected with the study drugs through an intravenous catheter placed in an arm vein. The PET scanner is shaped like a doughnut. Participants will lie on a bed that slides in and out of the scanner. A plastic mask will be molded to their head to keep them from moving. A thin plastic tube will be put into an artery at the wrist or elbow crease area. This will be used to draw blood during the scan. Participants will have 2-5 study visits. Participation lasts 1 week to 4 months, depending on scheduling.

Type: Interventional

Start Date: Aug 2021

open study

HQ-HTN-G01 is a prospective, multicenter, single arm, open label, early feasibility study to evaluate initial safety and device design concept of "HyperQureTM RDN System", laparoscopic renal denervation therapy, in patients with resistant hypertension on three(3) or more antihypertensive medications

Type: Interventional

Start Date: Nov 2024

open study