The swallowing muscles are prone to decreased strength and function as part of the natural aging process which can lead to difficulty swallowing, malnutrition, and frailty. Exercise and nutrition are powerful stimulators of muscular change. The proposed research will investigate the effectiveness of a 12-week proactive regimen of swallowing exercises (with or without daily protein supplement drinks) to improve the composition, force, and physiology of the swallowing muscles and explore the relationship to overall health and physical function in 80 community-dwelling older adults. Each participant will serve as their own control for 12 weeks before being randomized to complete swallowing exercises alone or swallowing exercises with protein drinks.

Type: Interventional

Start Date: May 2024

open study

This study aims to illuminate the biological underpinnings of negative symptoms in schizophrenia-particularly motivational impairments-by probing the link between systemic inflammation and neural activity in reward-related brain circuits. The primary goal of this study is to determine: - Ventral Striatum Activation: Assess how reward anticipation engages the ventral striatum in individuals with schizophrenia, both before and after an anti-inflammatory intervention. - Anterior Insula Activation: Examine how increasing effort demands modulate activity in the anterior insula under the same conditions.

Type: Interventional

Start Date: Apr 2024

open study

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: 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

Latino caregivers of individuals with Alzheimer's disease and related dementias experience high levels of stress burden and depressive symptoms and are underrepresented in caregiver intervention research. Tele Savvy is an evidence based caregiver education program that focuses on developing caregiver mastery skills. This study aims to culturally adapt the Tele Savvy intervention for Latino caregivers and evaluate its preliminary efficacy in a Stage 1b single arm clinical trial. The intervention is delivered remotely and includes weekly group sessions and asynchronous instructional videos. Primary outcomes focus on caregiver mastery with secondary outcomes including stress burden depressive symptoms and self efficacy.

Type: Interventional

Start Date: Apr 2026

open study

The purpose of the study is to learn about how effective, safe, and tolerable the Clostridioides difficile (C. difficile) vaccine is in decreasing the number of C. difficile infections (pCDI) in adults 65 years of age or older. The participants will receive either the C. difficile vaccine or placebo (saline). A placebo does not contain any active ingredients. The vaccines will be given as a shot into the upper arm muscle. This study looks at the number of diarrhea (loose stools) events related to a C. difficile infection, so the length of the study can change. If these events happen quickly, the study may finish sooner; if they happen slowly, it could take longer. Sometimes, the study might stop early if the vaccine clearly works or clearly doesn't. Participants will stay in the study until enough events have occurred to answer the main question. On average, each person is expected to take part for up to about three and a half years. During this time, participants will have 3 planned clinical visits and 3 planned phone visits. After these visits, more scheduled clinic visits will happen every year until the end of study. Besides the scheduled study visits, if at any time during the study a participant has 3 or more loose stools in 24 hours, they will be asked to save the next one (the fourth or later) and contact the study site. The study site will check to see if it could be a C. difficile infection. This check may happen at the clinic or through a phone or video call.

Type: Interventional

Start Date: Dec 2025

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

Chronic tics are a disabling neuropsychiatric symptom associated with multiple child-onset mental disorders. Chronic tics affect 1-3% of youth 1 and are associated with impaired functioning, emotional and behavioral problems, physical pain, diminished quality of life, peer victimization, and a fourfold increased risk of suicide compared to the general population. Large randomized trials have demonstrated the superiority of CBIT over supportive therapy in child and adult patients. However, in these trials, only 52% of children and 38% of adults showed clinically meaningful tic improvement, meaning that 50-60% of patients do not benefit from CBIT. CBIT success relies on an ability to suppress tics that many youth lack. The central aim of CBIT is to enhance voluntary tic suppression. Better tic suppression ability drives CBIT improvement 10 and predicts lower tic burden over the course of illness. During the core CBIT procedure, competing response training, patients learn to inhibit tics by engaging in a competing motor action. However, research shows that many youth lack this fundamental tic suppression ability that CBIT aspires to enhance. This study will examine the clinical and neural effects of a treatment combining Comprehensive Behavioral Intervention for Tics (CBIT) and transcranial magnetic stimulation (TMS) to the supplementary motor area (SMA) in young people with tic disorder.

Type: Interventional

Start Date: Feb 2025

open study

This research study is investigating whether people with Alzheimer's disease (AD) experience more changes to swallowing than their healthy age-matched peers. The prevalence of swallowing impairments in moderate-severe AD is high (85-93%), yet little is known about how swallow function evolves throughout the disease course in people with AD. The overall objective of this study is to evaluate swallowing function in adults with and without Alzheimer's disease. The investigator will also be involving the primary caregivers of individuals with Alzheimer's that are enrolled in the study to better understand the impact of swallowing impairments on the primary caregivers of those with Alzheimer's Disease. Healthy adults and individuals with Alzheimer's disease will: - undergo tests of cough and swallow function - undergo tests of grip and tongue strength - complete questionnaires Caregivers of individuals with Alzheimer's disease will also complete questionnaires.

Type: Observational

Start Date: Apr 2025

open study

The purpose of this study is to understand whether people with Parkinson's Disease and depression have improvement in their symptoms after psilocybin therapy.

Type: Interventional

Start Date: Aug 2024

open study

This study aims to identify how enhanced allopregnanolone activity (via pregnenolone) affects behavior and neurobiology that may underlie perimenopausal depression.

Type: Interventional

Start Date: May 2024

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

This study has two phases: Phase 1 is to examine blood pressure, microvascular function, and sympathetic nerve activity in mid-life adult binge drinkers vs. alcohol abstainers/moderate drinkers. Phase 2 is to examine the effect of 8-week aerobic exercise training on blood pressure, microvascular function, and sympathetic nerve activity in mid-life adult binge drinkers

Type: Interventional

Start Date: Nov 2022

open study

The Morphea in Adults and Children (MAC) cohort is the first registry for both children and adults with morphea (also known as localized scleroderma) in the country. The purpose of the registry is to learn more about morphea, specifically: - How morphea behaves over time - How frequently specific problems occur along with morphea (for example, arthritis) - Whether morphea has an autoimmune background

Type: Observational [Patient Registry]

Start Date: May 2007

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

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

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

Background: Influenza (flu) infections are a serious global health threat. Each year, between 3 and 5 million people get the flu, and up to 500,000 die from it. Current vaccines protect against seasonal flus, but broader vaccines are needed to protect against potential flu pandemics. Objective: To test an experimental flu vaccine. Eligibility: Healthy people aged 18 to 55 years. Design: The study will last 5 to 8 months and has 2 phases, A and B. The study vaccine will be given either as a shot in the arm or as a nasal spray. Participants will receive 1 of 3 combinations: (1) study vaccine in the nose and placebo in the arm; (2) placebo in the nose and study vaccine in the arm; or (3) placebo in the nose and placebo in the arm. A placebo is just like the real vaccine but contains no active ingredients. Phase A: Participants will have 5 clinic visits over 56 days. They will receive a shot and a nasal spray at 2 of the visits, 28 days apart. At each visit, they will have a physical exam, with tests of their blood, urine, and nasal secretions. They will check their temperature at home and record any symptoms for 7 days after each vaccine. Phase B: Participants will stay in the hospital for at least 9 days. They will be infected with a flu virus. They will provide blood, urine, and nasal fluid samples. They will have tests of their heart function. They will remain in the hospital until they test negative for the flu 2 days in a row. They will have 2 follow-up visits, 4 and 8 weeks after leaving the hospital. ...

Type: Interventional

Start Date: Jun 2026

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: Aug 2025

open study

Stage 2 Type 1 Diabates (T1D) is an early stage of T1D characterized by dysglycemia but not yet leading to clinical symptoms. Progression of the disease to Stage 3 (clinical T1D), leads to overt hyperglycemia requiring eventually exogenous insulin. TZIELD® (teplizumab-mzwv) has been approved to delay onset of stage 3 T1D, by the United States (US) Food and Drug Administration (FDA) for adults and children aged 8 years and older with Stage 2 T1D. The purpose of this study is to collect general information on patients with stage 2 T1D and further information on the long-term effects of TZIELD® in patients with Stage 2 T1D, treated as per standard of care.

Type: Observational

Start Date: Sep 2024

open study

The goal of this clinical trial is to test whether an adaptation of an evidence-based, couple-based preventive intervention at the transition to parenthood improves reduces obesity risk among infants and parents in military families via improved interparental support and coordination around health lifestyle behaviors and parenting. The main question it aims to answer is whether an adapted, innovative family-focused approach to obesity prevention can reduce rapid infant weight gain, new mothers' postpartum weight retention, and fathers' weight status. Participants randomized to the Healthy Family Foundations (HFF) intervention condition will participate in 10 online group classes (5 prenatal and 5 postnatal). Participants randomized to the control condition will receive standard of care and opportunities for education at their site. Researchers will compare the Healthy Family Foundations (HFF) intervention group with a Standard of Care control group to see if there are differences in weight, coparenting support, parent mental health and parent health behaviors.

Type: Interventional

Start Date: May 2023

open study

The goal of this project evaluate the efficacy of NiteCAPP in improving insomnia in a rural dementia caregiver sample (n of 100 caregiver and PWD dyads). We will measure both the short term (post-treatment) and long term (6 and 12 months) effects of the intervention on CG sleep, arousal, inflammation, health, mood, burden and cognitive function, and PWD sleep.

Type: Interventional

Start Date: Feb 2022

open study

The aim of this trial is to evaluate whether testosterone replacement results in greater improvement in pain perception, pain tolerance, sexual function, fatigue, and quality of life when compared with placebo in men with chronic spinal pain treated with opioids who have opioid-induced hypogonadism (low testosterone).

Type: Interventional

Start Date: Jan 2022

open study

Background: - Like other complex diseases, autoimmune diseases are the result of numerous causes, including genetic and environmental factors. Some researchers believe that people who are susceptible to autoimmune disorders develop them when the body reacts to environmental or other factors by creating white blood cells that attack the body s own tissues, which then progresses to autoimmune diseases. These immune-triggered disorders can overlap with one another to some extent, but most autoimmune diseases have certain distinct triggers. - The autoimmune disorder myositis weakens the muscles and may cause other health problems. Environmental exposures associated with myositis include ultraviolet radiation, stressful life events and muscle overexertion, collagen implants, infections such as retroviruses and streptococci bacteria, and certain drugs and chemicals. Some individuals with myositis also produce proteins in the blood called autoantibodies that react with certain parts of the person s own cells, called synthetases, which are involved in making new proteins. A syndrome called the anti-synthetase syndrome, which includes myositis and lung disease, is associated with having the anti-synthetase autoantibodies. Researchers are interested in studying differences in environmental exposures in individuals with myositis. This study is being conducted to determine if persons with the anti-synthetase syndrome have had different environmental exposures before disease onset compared with other patients with myositis who do not have this syndrome and also compared with healthy volunteers. Objectives: - To determine whether selected infectious and noninfectious environmental exposures are more common in individuals who have myositis with the anti-synthetase syndrome, compared with healthy volunteers. Eligibility: - Individuals who have been diagnosed with myositis (with or without anti-synthetase autoantibodies), and healthy volunteers without autoimmune disorders. Design: - Participants will be screened with a full medical history and physical examination, and will provide blood, urine and house dust samples. - Participants will complete questionnaires about their medical history and the types of exposures they have had at work, at home, and elsewhere. Participants who have myositis will also be asked about certain infections, heavy exercise or physical exertion, sun exposure, tobacco and alcohol use, and stressful events prior to being diagnosed with the disease. Healthy volunteers will be asked about the same exposures before the date of diagnosis of disease of the myositis subject to which they have been matched. - Participants will receive a kit that contains instructions and a filter to be put onto their vacuum cleaner to collect house dust in the bedroom. This dust will be kept for possible future analyses of infectious or toxic agents based on the other results from the study. - Individuals with myositis will have other tests as clinically indicated, including lung function tests and imaging studies.

Type: Observational

Start Date: Feb 2011

open study