Background: Sickle cell disease (SCD) is an inherited blood disorder. The disease affects the ability of red blood cells to carry oxygen. Research has shown that curcumin, a natural compound found in turmeric, can improve the health of red blood cells in people with SCD. But the body cannot absorb curcumin well when it is taken by mouth. Researchers want to know if a skin gel (VAS-101) can help the body better absorb curcumin. VAS-101 contains curcumin, which comes from turmeric. Objective: To test VAS-101 in people with stable SCD. Eligibility: People aged 18 to 70 years with stable SCD. Design: People who want to join the study will be screened with physical exam with blood tests to see if they are eligible. If they qualify, they can enroll in the study. Participants will have up to 15 clinic visits over about 14 weeks. Some may need to stay overnight in the hospital for up to 2 days to make it easier to collect blood samples after the gel is applied. For 6 weeks, a special gel called VAS-101 will be put on the forearms in the clinic two times a week. Staff will rub the gel into the skin for at least 30 seconds using a soft toothbrush. The area stays uncovered for at least 10 minutes, then is covered with a bandage or sleeve. After 24 hours, the dressing can be removed and the skin can be washed. Some visits will include blood tests and other exams. On three visits, a test called near infrared spectroscopy (NIRS) will be done. For this test, probes are placed on the skin to measure blood flow, oxygen levels, and the makeup of skin and muscle. A blood pressure cuff is used to squeeze the arm for up to 5 minutes. The last clinic visit will happen about 4 weeks after the final gel application....

Type: Interventional

Start Date: Aug 2026

open study

Background: - Researchers who are studying hairy cell leukemia, and how the disease compares with other disorders, are interested in obtaining additional samples from leukemia patients and healthy volunteers. The investigators are particularly interested in samples from individuals who have diseases that can be treated with a new type of drug called immunotoxin, in which an antibody carrying a toxin binds to a cancer cell and allows the toxin to kill the cell. Objectives: - To collect a variety of clinical samples, including blood, urine, lymph samples, and other tissues, in order to study the samples and develop new treatments for leukemia. Eligibility: - Individuals 18 years of age and older who have been diagnosed with leukemia or other kinds of blood and lymphatic system cancers, or who are healthy volunteers. Design: - Individuals who have leukemia will be asked to provide blood, bone marrow, urine, and tumor tissue samples as requested by the researchers. Healthy volunteers will provide only blood and urine samples. - No treatment will be given as part of this protocol.

Type: Observational

Start Date: Mar 2010

open study

Methylmalonic acidemia (MMA), one of the most common inborn errors of organic acid metabolism, is heterogeneous in etiology and clinical manifestations. Affected patients with cblA, cblB and mut classes of MMA are medically fragile and can suffer from complications such as metabolic stroke or infarction of the basal ganglia, pancreatitis, end stage renal failure, growth impairment, osteoporosis, and developmental delay. The frequency of these complications and their precipitants remain undefined. Furthermore, current treatment protocol outcomes have continued to demonstrate substantial morbidity and mortality in the patient population. Increasingly, solid organ transplantation (liver, and/or kidney) has been used to treat patients. Disordered transport and intracellular metabolism of vitamin B12 produces a distinct group of disorders that feature methylmalonic acidemia as well as (hyper)homocysteinemia. These conditions are named after the corresponding cellular complementation class - (cblC, cblD, cblF, cblJ and cblX) - and are also heterogenous, clinically and biochemically. The genetic disorders underlying cblE and cblG feature an isolated impairment of the activity of methionine synthase, a critical enzyme involved in the conversion of homocysteine to methionine and these disorders feature (hyper)homocysteinemia. Lastly, a group of patients can have increased methylmalonic acid and/or homocysteine in the blood or urine caused by variant(s) in recently identified (ACSF3) and unknown genes. In this protocol, we will clinically evaluate patients with methylmalonic acidemia and cobalamin metabolic defects. Routine inpatient admissions will last up to 4-5 days and involve urine collection, blood drawing, ophthalmological examination, radiological procedures, MRI/MRS, skin biopsies in some, and developmental testing. In a subset of patients who have or will receive renal, hepato- or hepato-renal transplants or have an unusual variant or clinical course and have MMA, a lumbar puncture to examine CSF metabolites will be performed. In this small group of patients, CSF metabolite monitoring may be used to adjust therapy. The study objectives will be to further delineate the spectrum of phenotypes and characterize the natural history of these enzymopathies, query for genotype/enzymatic/phenotype correlations, search for new genetic causes of methylmalonic acidemia and/or homocysteinemia, identify new disease biomarkers and define clinical outcome parameters for future clinical trials. The population will consist of participants previously evaluated at NIH, physician referrals, and families directed to the study from clinicaltrials.gov as well as the Organic Acidemia Association, Homocystinuria Network America and other national and international support groups. Most participants will be evaluated only at the NIH Clinical Center. However, if the NIH team decides that a patient under the age of 2 years is a candidate subject for this research protocol, that patient may enroll at the Children's National Medical Center (CNMC) site, pending approval by Dr Chapman, the Principal Investigator of the CNMC location Individuals may also enroll in the tissue collection only part of the study at the UPMC Children's Hospital of Pittsburgh or share medical history and clinical data via telemedicine visits remotely. Outcome measures will largely be descriptive and encompass correlations between clinical, biochemical and molecular parameters.

Type: Observational

Start Date: Jun 2004

open study

Background: Phosphodiesterase-4B (PDE4B) is a protein in the brain that may play a role in several mental health disorders. Researchers want to know if drinking alcohol increases the binding of a radioactive tracer to PDE4B in the brain because of increased activity and/or amount of the protein. This knowledge may help create new ways to treat people with alcohol use disorder (AUD). Objective: To learn if alcohol increases PDE4B activity in the brain. Eligibility: Healthy people aged 21 to 70 years who drink socially but do not have AUD. They must be enrolled in protocol 14-AA-0181"NIAAA Natural History Protocol". Design: Participants will have up to 4 clinic visits with up to 3 imaging scans of the brain; these will include 1 or 2 positron emission tomography (PET) scans and 1 magnetic resonance imaging (MRI) scan. The first PET scan will be a baseline. Participants will receive a radioactive tracer through a tube inserted into a vein. A second tube will be inserted so that blood can be drawn during the scan. Participants will lie on a bed that slides into a doughnut-shaped machine. This visit will take about 6 hours. For the next PET scan, participants will receive alcohol (ethanol) through a tube in a vein until they have a blood alcohol concentration that is equal to the legal driving limit. This is the same as 4 or 5 drinks for most people. After the scan, participants must remain at the clinic for a few hours until their blood alcohol drops. This visit will take 14 to 16 hours. The MRI scan of the brain will take up to 2 hours in a separate clinic visit.

Type: Interventional

Start Date: Dec 2025

open study

Background: SARS-CoV-2 is the virus that causes COVID-19. Some people who recover from COVID-19 have long-term symptoms that affect the brain. These include headaches; loss of taste and smell; sleep problems; thinking problems; depression; and anxiety. Researchers want to know if a tracer (a substance that is injected into a person s body before an imaging scan) can help identify inflammation in people with these brain disorders. Objective: To see if a radioactive tracer ([11C]PS13) can highlight brain inflammation in those who had COVID-19 but still have symptoms that affect the brain. Eligibility: Adults aged 18 to 70 years with post COVID-19 brain disorders who are enrolled in protocol 000089 or 000711. Healthy volunteers are also needed. Design: Participants will have up to 5 clinic visits. Participants will be screened. They will have blood tests and a test of their heart function. They will have imaging scans: Magnetic resonance imaging (MRI): They will lie on a table that slides into a metal tube. Pictures will be taken of the brain. Positron emission tomography (PET): A needle attached to a thin tube will be inserted into a vein in the arm. The tracer will be injected through the tube. Another needle attached to a thin tube will be inserted into the wrist or inside of the elbow of the other arm to draw blood. They will lie still on a bed while a machine captures images of their brain. The scan will last about 2 hours. Study involvement is 11 to 14 weeks....

Type: Interventional

Start Date: Jun 2025

open study

Background: Children with attention deficit hyperactivity disorder (ADHD) often have cognitive problems. It may be hard for them to control their behaviors, concentrate for long periods, or make decisions. This can affect their education, friendships, and daily life. Virtual reality-based games may help improve cognitive skills in children with ADHD. It may also help change how the brain functions. Objective: To see if virtual reality-based games help improve thinking skills and brain function in children with ADHD. Eligibility: Children aged 8 to 16 years with ADHD. Design: We will first do a pilot study, meaning that everyone will receive the games. If this is successful, we will then conduct a randomized controlled trial, meaning that some participants will be randomly assigned to the full version of the games and some will be randomly assigned to a limited version. Participants will be screened. Their physical and mental health, medical and family history, and intellectual and emotional development will be evaluated. They will have tests of their mood, memory, attention, thinking, and behavior. Blood or saliva may be collected. Participants may have an MRI scan of the brain. Participants will receive a set of virtual reality games. The set includes 4 different games all played using a virtual reality headset. The participant will play the games for 20 minutes 5 days a week for 4 weeks. The parent or caregiver will start each game using an iPad. Each of the games is designed to help the participant practice specific cognitive skills. These include inhibition control, processing speed, temporal information processing, and working memory. Participants will have interviews each week. They will answer questions about motion sickness, eye strain, headache, and any other side effects, as well as number of game sessions played. Blood or saliva tests and the MRI may be repeated after the last game session. For the pilot, participants will have a final interview at the study end. For the full trial, a 1-month follow-up visit will be done by telehealth.

Type: Interventional

Start Date: Mar 2024

open study

Background: One way to treat liver cancer is to deliver chemotherapy drugs only to the liver (and not to the whole body). Researchers want to see if adding the drug PDS01ADC can improve the treatment. The drug triggers the immune system to fight cancer.<TAB> Objective: To see if treatment with HAIPs to deliver liver-directed FUDR and Dexamethasone chemotherapy in combination with PDS01ADC is effective for certain cancers. Eligibility: People aged 18 and older who have cancer of the bile ducts that is only in the liver, or colorectal cancer that has spread to the liver, or cancer of the adrenal glands that has spread to the liver, who are also receiving or planning to receive standard systemic chemotherapy for their disease. Design: Participants will be screened with: Medical history Physical exam Blood tests Pregnancy test (if needed) Tumor biopsy (if needed) Electrocardiogram Computed tomography (CT) scans Participants will have an abdominal operation. A catheter will be placed into an artery that feeds blood to the liver. The catheter will then be attached to the HAIP. The HAIP will lay under the skin on the left side of the abdomen. All participants will have liver-directed FUDR and Dexamethasone chemotherapy drugs or heparin with saline infused into the HAIP every 2 weeks. PDS01ADC will be injected under the skin every 4 weeks. They will receive this treatment until their cancer gets worse or they have bad side effects. Participants will also receive standard systemic chemotherapy for their disease, assigned based on diagnosis, through an IV by their medical oncologist (at NIH or by a local provider) every 2 weeks. Participants will have 2 study visits at NIH each month. They will have CT scans every 8 weeks. At visits, they will repeat some screening tests. Participants will have a follow-up visit 1 month after treatment ends. Then they will be contacted every 6 months for 5 years.

Type: Interventional

Start Date: Oct 2022

open study

This study will investigate how genetic and environmental factors contribute to the development of melanoma, a type of skin cancer, and related conditions. Individuals >=4 weeks with a personal or family history of melanoma or atypical spitzoid/Spitz tumor may be eligible for this study. Participants will: - Fill out one or two questionnaires about their personal and family medical history. - Provide written consent for researchers to review their medical records and pathology materials related to their care and those of deceased relatives with melanomas, tumors, cancer, or other related illnesses for whom they are the next-of-kin or legally authorized representative. - Donate a blood or cheek cell sample to be used for genetic studies. (The blood sample is collected through a needle in an arm vein. The cheek cell sample is obtained either by gently brushing the inside of the mouth with a soft brush or by swishing a tablespoon of mouthwash and then spitting it into a container.) - Undergo a skin biopsy (removal of a small piece of skin tissue) for genetic study. For this procedure, the area of skin to be removed is numbed with a local anesthetic and a 1/4-inch piece of skin is excised with a cookie cutter-like instrument. The wound is then covered with a band-aid. Participants may be asked to travel to the NIH Clinical Center for evaluation, including a medical history, physical examination, and some of the following procedures: - Full body skin examination to evaluate the type and number of moles and document any evidence of sun damage to the skin. The examination involves all the skin from the scalp to the bottoms of the feet. After the examination, a medical photographer will photograph the skin, with close-ups of skin lesions marked by the examiner. If there are parts of the skin the participant does not want examined or photographed, he or she can tell the examiner. - Blood draw of about 120 milliliters (4 ounces) or less - Skin biopsy - Cheek cell sample - X-rays, ultrasound and magnetic resonance imaging (MRI) studies to detect tumors or changes in tumors or other types of changes in specific tissues. MRI is a diagnostic test that uses strong magnetic fields and radiowaves to examine body tissues. The subject lies on a table that is moved into a large tunnel-like machine (the scanner) for about 45 minutes to 1 hour. When the tests are finished, a doctor will discuss the results with the participant and the need, if any, for clinical follow-up.

Type: Observational

Start Date: Jul 2002

open study

This study is a double-blind, randomized, parallel group, three-arm, placebo-controlled trial of seventy-five (75) apparently healthy male and female participants to be recruited at a single investigational center in Northeast Ohio (i.e., The Center for Applied Health Sciences). The study will assess the potential benefits of four weeks of supplementation with 300 mg Ginseng or 1 gram Cordyceps Militaris (vs. placebo). Participants will attend 3 study visits. During Visit 1, participants will be screened for participation (i.e., medical history, routine blood work, background baseline diet and familiarization protocol will be completed). During Visit 2 (Day 0) and Visit 3 (Day 30) participants will complete subjective baseline testing including questionnaires that assess recovery, mood, energy, fatigue, and quality of life. They will complete a VO2 max test, a TTE test, isometric mid-thigh pull, and have their handgrip strength assessed. They will also be tested for changes in circulating nitrates/nitrites (NOx), circulatory efficiency (oxygen pulse), and lactate kinetics (production and clearance). Comprehensive side effect profile/ adverse event monitoring will take place throughout thevstudy duration. The study will be conducted following ICH-GCP guidelines to ensure subject safety and scientific integrity of the data.

Type: Interventional

Start Date: Mar 2026

open study

The research study will evaluate how the body absorbs and reacts to reformulated Levulan Kerastick when applied to actinic keratosis lesions (AKs) on the skin of the forearms or face followed by photodynamic therapy (PDT), a treatment that uses application of blue light.

Type: Interventional

Start Date: Aug 2026

open study

The study tests ATTN201, an investigational non-invasive headband that delivers low-intensity focused ultrasound (LIFU) to the subthalamic nucleus (STN) as a treatment for obsessive-compulsive disorder (OCD). It's a randomized, double-blind, 1:1 (active: sham) study with 40 total participants spanning 12-16 weeks and 14 in-person and remote visits.

Type: Interventional

Start Date: Jul 2026

open study

Screen2Prevent is a study intended to improve HIV prevention and detection through implementation and evaluation of three different broad-scale HIV screening approaches a) targeted, b) universally offered opt-in, and c) universally offered opt-out in Emergency Departments (EDs) by leveraging digital health to identify and link adolescents seeking care in the ED to HIV Pre-Exposure Prophylaxis (PrEP)/Antiretroviral treatment (ART).

Type: Interventional

Start Date: Jun 2026

open study

This pilot clinical trial will evaluate whether intentional chewing of a standardized hard chewing gum for 4 weeks produces measurable changes in facial morphology in healthy adults. Twenty participants aged 20-40 years will undergo three-dimensional facial imaging (3dMD) at baseline (T0), after the 4-week chewing intervention (T1), and following a 4-5-week washout period (T2). Changes in facial soft-tissue morphology will be assessed using three-dimensional surface analysis, including heatmaps, regional surface displacement, and morphometric measurements. Secondary outcomes include self-reported muscle fatigue, soreness, adherence, and temporomandibular disorder (TMD) symptoms.

Type: Interventional

Start Date: Jun 2026

open study

The goal of this clinical trial is to compare the standard programming of the VNS device (Control) to a modified programming (Augusta Way) in adults with epilepsy. The main question it aims to answer is: Does the modified programming of the VNS reduce seizures faster than the standard programming? Participants in both groups will: 1. Attend up to 3 study visits every 3 months for 2 years 2. Answer questionnaires to assess quality of life and cognitive function 3. Maintain a diary of seizure activity

Type: Interventional

Start Date: Aug 2025

open study

This study evaluates a new digital health program that uses artificial intelligence (AI) to help patients lower their blood pressure through personalized lifestyle recommendations. The program collects information about patients' daily habits and blood pressure readings, then uses AI to suggest lifestyle changes that may work best for each person. The study will measure how well this program works across different groups of patients and aims to improve the program design to make it more effective and easier to use. The program will be offered to diverse patients at UC San Diego Health, including people of different ages, genders, races/ethnicities, and economic backgrounds, as part of their regular healthcare services.

Type: Interventional

Start Date: Apr 2026

open study

This study aims to evaluate the effects of 2 weeks of inulin supplementation in perimenopausal women with overweight or obesity. The primary questions this study seeks to answer are: 1. Does 2 weeks of inulin supplementation alter the gut and vaginal estrobolome compared with placebo? 2. Does 2 weeks of inulin supplementation affect cardiovascular health compared with placebo? 3. Does 2 weeks of inulin supplementation affect skeletal muscle health compared with placebo? Researchers will compare inulin with a placebo (a similar-looking supplement that does not contain inulin) to determine whether inulin influences gut and vaginal microbial function, cardiovascular health, and skeletal muscle health during the perimenopausal transition. Participants will: - Take either inulin or a placebo for 2 weeks, followed by a 2- to 4-week washout period, and then switch to the other supplement for an additional 2 weeks. - Attend 8 study visits over approximately 12 to 16 weeks for assessments and sample collection. - Complete weekly phone calls to monitor symptoms, supplement adherence, and dietary intake. - Wear a Fitbit device throughout the study to monitor physical activity.

Type: Interventional

Start Date: Jul 2026

open study

The goal of this clinical trial is to learn if digital recovery support services (such as smartphone app) help to support alcohol recovery. We focus on a community of Black and African American people with alcohol use disorder (AUD) who receive in-person recovery support services from a recovery community center. Participants will: - Have an initial 2-hour in-person visit with the research team. During this visit, participants will be asked about themselves and their recovery from alcohol problems. They will also learn about digital recovery resources. - Use digital recovery resources on their own for 12 weeks. - Complete a short, weekly survey about their experience using digital recovery resources. - Have a follow-up 1-hour in-person visit where the researcher asks about again about the participants, their recovery and how they felt about using the digital recovery support services.

Type: Interventional

Start Date: Jun 2026

open study

The purpose of Study LX2006-03, a multicenter, Phase 2, open-label, randomized, controlled study, is to evaluate the efficacy and safety of LX2006 gene therapy in participants with Friedreich ataxia (FA) cardiomyopathy (CM).

Type: Interventional

Start Date: Jun 2026

open study

This study will investigate how two inhaled essential oil products (QueaseEASE and STILL) and a wearable transcutaneous electrical nerve stimulation (TENS) device (ReliefBand) affect chronic nausea and anxiety in adults with longstanding nausea. The goal is to better understand the mechanisms by which these non-prescription therapies may influence nausea, anxiety, sleep, pain, autonomic symptoms, and bowel-related symptoms. Participants will first complete a 2-week baseline period during which nausea and other symptoms are assessed through questionnaires. Participants will then use the inhaled essential oil products as needed for 12 weeks while completing symptom surveys. Afterward, participants will use the ReliefBand wearable TENS device as needed for an additional 12 weeks and continue completing surveys. Researchers will compare symptom changes during the intervention periods with baseline measurements to better understand factors that contribute to chronic nausea and how these therapies may provide relief. Up to 250 participants may be enrolled to achieve approximately 100 participants completing both intervention phases

Type: Interventional

Start Date: May 2024

open study

ariessence is intended to be used as a viscous, leave-on solution designed for topical application to the face. It is intended to be used following non-medical cosmetic procedures, performed by licensed healthcare professionals to enhance comfort and maintain skin hydration. This study is designed to be a multi-center, post-market cosmetic evaluation of ariessence applied to the full face after an ablative laser procedure to evaluate improvements in procedure tolerability and improvements in the appearance of the skin, compared to an emollient control.

Type: Interventional

Start Date: Apr 2026

open study

Single center, double-masked study of BL1332 on Capsaicin-Induced Ocular Pain in Healthy Subjects

Type: Interventional

Start Date: Jul 2026

open study

This study is a Phase 3, multi-center, randomized, 6-week, double-blind, placebo-controlled, parallel-group trial to assess the efficacy and safety of solriamfetol in adolescents aged 12 to <18 years with ADHD.

Type: Interventional

Start Date: Jun 2026

open study

The purpose of this study is to evaluate the preliminary efficacy, feasibility, acceptability, and barriers and facilitators to implementation of the Confident Caregiver intervention among family caregivers of persons with cardiovascular disease participating in cardiac rehabilitation. Caregivers receive four individualized intervention sessions focused on assessment of caregiving challenges, tailored coaching, stress reduction, education, and referrals to supportive resources. Outcomes include reductions in caregiving-related challenges, improvements in mental health, and reductions in stress.

Type: Interventional

Start Date: Jul 2026

open study

An open-label study to evaluate the safety and efficacy of KB111 in pediatric and adult subjects with Hailey-Hailey Disease

Type: Interventional

Start Date: May 2026

open study

Patients with obstructive sleep apnea (OSA) often experience more frequent and severe breathing disturbances when sleeping in the supine (back-sleeping) position compared with non-supine positions. Positional therapy aims to reduce time spent sleeping in the supine position, but existing treatment options may be limited by comfort and effectiveness. This study evaluates the effectiveness and usability of WhisperPT, an investigational in-ear positional therapy device that delivers gentle audio cues during sleep to encourage participants to move from the supine to a non-supine sleeping position. The study will assess the device's ability to reduce the apnea-hypopnea index (AHI), decrease time spent sleeping supine, and evaluate participant comfort and ease of use.

Type: Interventional

Start Date: Jun 2026

open study