Study Description: Despite the availability of pharmacotherapy for some substance use disorders, relapse vulnerability is still a significant issue. This suggests medications with alternative mechanisms of action should be explored to address this unmet need. Substantial preclinical research indicates that orexin antagonism blunts the internally and externally triggered motivation to attain abused substances. This research project will translate these preclinical findings into the clinical domain by administering the FDA approved orexin antagonist, suvorexant, to those with a substance use disorder. Suvorexant s ability to blunt neurobiological correlates of substance misuse will be assessed. This will be assessed following acute and repeated drug administration. Baseline individual differences will be considered to determine whether neurobiological variance influences suvorexant s impact in those with nicotine dependence. In an independent arm, the interaction between suvorexant and a dopamine agonist (methylphenidate) on cognitive function will be assessed in non-smoking individuals. Objectives: The objective is to determine the acute and chronic impact of the orexin antagonist, suvorexant, on neurobiological and behavioral factors linked with substance use disorders. Whether such effects are mediated by baseline characteristics will be tested. Given suvorexant is an FDA approved treatment for insomnia, sleep will be evaluated as well in the nicotine dependent arm. Endpoints: In nicotine-dependent individuals, suvorexant s impact on brain function will be assessed several ways by evaluating: 1) resting function, 2) reactivity to drug cues, 3) reactivity to non-drug related cognitive tasks. Sleep and nicotine use will be measured throughout the study period. In those without nicotine-dependence, the impact of suvorexant and the interaction of acute methylphenidate and suvorexant on brain function will be assessed. This arm will provide insight into how suvorexant impacts reward/cognition as well as impacts the pharmacological influence of methylphenidate on those same measures. Study Population:<TAB> Nicotine dependence arm:140 subjects; Volunteers who are between the ages of 18-60 and are daily smokers/vapers. Control arm: 80 subjects; Volunteers who are between the ages of 18-60 and are non-smokers/vapers This study will be conducted at the NIDA-IRP, Biomedical Research Center, in Baltimore, MD. Description of Study Intervention: Nicotine dependence arm: Suvorexant at 10 mg single dose, and Suvorexant at 10 mg daily for approximately 7 days. Control arm: 1. Tolerability visit with one MRI scan post-20mg methylphenidate, 4 acute drug administration (6-14 days in randomized order: 1. Placebo + placebo; 2. 20mg suvorexant + Placebo; 3. Placebo + 40mg methylphenidate; 4. 20 mg suvorexant + 40mg methylphenidate max) Study Duration: 5 years Participant Duration: 1-2 months

Type: Interventional

Start Date: Feb 2023

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 is a multicenter, genetically-randomized, controlled, Phase 3 study evaluating the efficacy and safety of T-cell receptor-engineered donor T cells targeting HA-2 (TSC-101) administered following reduced-intensity conditioning (RIC) hematopoietic cell transplantation (HCT) in participants with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS). The study will compare TSC-101 plus standard of care (SOC) versus SOC alone in participants undergoing allogeneic peripheral blood stem cell transplantation from haploidentical or mismatched unrelated donors.

Type: Interventional

Start Date: Jun 2026

open study

This study examines how adults who take a GLP-1 receptor agonist medication (such as semaglutide [Ozempic, Wegovy, Rybelsus], liraglutide [Saxenda, Victoza], or tirzepatide [Mounjaro, Zepbound]) perform resistance (strength) training before and after starting their medication. GLP-1 medications are being prescribed more and more often to help people manage type 2 diabetes and lose weight. These medications work well, but a known side effect is that people can lose lean (muscle) tissue along with fat. Losing muscle can make it harder to move, do everyday tasks, and stay strong as we age. Resistance training, things like lifting weights, using resistance bands, or doing push-ups and squats, is the most effective way to keep and build muscle. Yet most adults in the United States do not meet the recommended amount of resistance training, and very little is known about the resistance training habits of people who take GLP-1 medications. The purpose of this research is to systematically collect information from adults using GLP-1 medications so we can better understand: how often they do resistance training before and after starting the medication; what their sessions look like (frequency, duration, intensity, muscle groups); whether their resistance training is linked to how strong they feel and how well they can carry out daily activities; and what makes resistance training easier or harder while on a GLP-1 medication. Findings will help doctors, dietitians, exercise professionals, and researchers design better guidance and interventions to protect muscle mass, physical function, and quality of life in people using GLP-1 medications. Who can join: Adults 18 years or older who are currently taking a GLP-1 receptor agonist medication for type 2 diabetes, overweight or obesity, or weight management, and who have been on the medication for at least three months at a stable dose. Participants must be able to read and respond to the survey in English. People who are pregnant or planning bariatric surgery within the next three months are not eligible. What participants will do: The study is a single, anonymous, online survey. Interested individuals click the survey link, review a short consent page, and indicate their willingness to participate. Eligible participants then answer questions about their background, current health, GLP-1 medication and dose, resistance training habits before and after starting the medication, self-reported strength and function, and things that make resistance training easier or harder. There are no in-person visits, no exercise tests, and no blood draws. How long it takes: About 10 minutes total, in one online session. There is no follow-up after the survey and no compensation is offered. Data privacy: The survey is anonymous. No names, email addresses, or IP addresses are collected or linked to responses. The survey runs on Qualtrics, a secure, institution-approved platform hosted on Ohio State University servers. The research team hopes to enroll up to 200-300 adults across the United States.

Type: Observational [Patient Registry]

Start Date: Jun 2026

open study

The goal of this study is to determine the whether a short-term, high-dose form of non-invasive brain stimulation (intermittent theta burst stimulation; iTBS) is a promising and safe treatment for mild cognitive impairment in Parkinson's disease (PD-MCI).

Type: Interventional

Start Date: Aug 2026

open study

The goal of this observational study is to evaluate the long-term safety and wound healing durability (up to 15 years) for participants with Recessive Dystrophic Epidermolysis Bullosa (RDEB) who were treated with pz-cel. The main questions it aims to answer are: - The long-term safety profile of pz-cel. - The wound healing durability of pz-cel. - The occurrence of all malignancies after treatment with pz-cel, regardless of type or location, in individuals who received pz-cel treatment for RDEB in the post-marketing setting. Participants will then be followed annually up to 15 years post-treatment. Assessments will occur via remote data collection. If the participants provider determines an office visit is necessary after the first year, some of this data can be collected in person as well. Annual assessments will include, but are not limited to: - Review of Adverse Events (AEs), Serious Adverse Events (SAEs), hospitalizations, and any evidence of malignancies and potential retroviral infection - Wound-healing durability data collection via the modified Caregiver Global Impression of Change for Wound Healing - Any changes in concomitant medications and procedures.

Type: Observational [Patient Registry]

Start Date: Jul 2025

open study

The goal of this clinical trial is to determine if perfusion index (PI) can reliably predict changes in systolic blood pressure (SBP) in persons with spinal cord injury (SCI) during a cool temperature challenge. Participants with SCI can be 18-75 years of age, male or female, neurological level of injury C4-T12, ASIA Impairment Scale (AIS: A or B: motor complete) or gender and healthy age-matched able-bodied (AB) controls. The main question this study aims to answer is: can PI reliably predict change in SBP during a cool temperature challenge? We hypothesize that PI can be used as a biomarker of SBP in persons with SCI. Researchers will compare the relationship of 1) changes in PI and SBP and 2) relationship of changes in other vital signs to SBP, during the cool temperature challenge. The researchers aim to determine if PI can be used as a biomarker of SBP in persons with SCI during a cool temperature challenge (experimental group/arm). Able-bodied controls (control group/arm) will receive the same intervention (cool challenge) as the experimental group. During the study, participants will be asked to wear only shorts and a T-shirt so that their skin can be exposed to the warm and cool temperatures of the 2 rooms. We will put put on non-invasive sensors (taped or attached on the surface of your body) to measure PI, BP, and other vital signs. We will record these measurements while you are seated in a wheelchair for 10 minutes in a warm room and up to 90 minutes in a cool room.

Type: Interventional

Start Date: Jul 2026

open study

The investigators propose to implement and evaluate the effectiveness of the peer-led CARE Intervention designed to mitigate health differences among rural and low-income communities in Texas. This intervention leverages the expertise of Community Health Workers (CHWs) to empower rural and low-income communities, improving health outcomes through outreach, education, counseling, and social support.

Type: Interventional

Start Date: Jun 2026

open study

This study will evaluate the safety and effects, good or bad of faricimab (Vabysmo®), a drug that is approved by the U.S. Food and Drug Administration (FDA) for other retinal conditions, but its use is considered investigational when used specifically for choroidal neovascularization (CNV) related to presumed ocular histoplasmosis (POHS)

Type: Interventional

Start Date: Jul 2026

open study

The purpose of this study is to evaluate the safety, tolerability, and efficacy of MZE782 in adults with Phenylketonuria (PKU).

Type: Interventional

Start Date: Jun 2026

open study

The goal of this observational study is to learn if there are potential digital and plasma-based biomarkers that could help detect, predict, and prognosticate delirium in older adult patients who are admitted to the intensive care unit (ICU). The main question DELTA aims to answer is: Can digital biometrics predict and detect delirium in older adult ICU patients? Do biomarkers of neurodegeneration fluctuate in ICU patients in such a way that delrium could potentially be predicted? Participants admitted o the ICU will wear a digital device to collect biometric data and will have serial plasma samples collected during ICU admission and patients will be also assessed for delirium daily by study staff.

Type: Observational

Start Date: May 2026

open study

This study is to assess safety, tolerability, pharmacokinetics (PK), pharmacodynamic (PD), and preliminary efficacy of ARC-02.

Type: Interventional

Start Date: Jun 2026

open study

The researchers are doing this study to test the capabilities of a new total-body PET scanner called the Biograph Vision Quadra. The researchers want to learn whether this scanner can produce better PET/CT images and provide more useful imaging information than standard PET/CT scanners.

Type: Observational

Start Date: Jun 2026

open study

This is an interventional study that will test whether a breathing exercise called Inspiratory Muscle Strength Training (IMST) can safely and effectively lower blood pressure during late pregnancy. The goal is to see if a home-based breathing training can help prevent or reduce high blood pressure disorders in pregnancy. The main objectives are to make sure the training is safe and tolerable for pregnant women and to examine blood pressure and blood vessel health. Participants in their third trimester will be randomly assigned to either do moderate resistance IMST or a minimal resistance sham IMST, for 5 to 8 minutes a day over six weeks.

Type: Interventional

Start Date: Jun 2026

open study

Background: Trisomy 8 mosaicism is a genetic disorder that can increase inflammation in the body. Symptoms include fevers; sores or ulcers in the mouth, digestive tract, or genital area; skin rashes; problems in organs or tissues; and changes in bone marrow cells. Researchers want to conduct a natural history study to learn more about these symptoms and what causes them. Objective: To gather data and samples from people with and without the trisomy 8 mosaicism. Eligibility: People of any age with the trisomy 8 gene mosaicism. Their healthy relatives are also needed. Design: Affected participants will have visits every 1 to 2 years for 30 years at NIH. Each visit will take 1 to 5 days and may be in-person or remote. With remote visits, participants may have a video call with the study team and samples may be sent to researchers by mail. Participants may have these procedures: Physical exam, with blood tests. Tests of brain function and motor skills. Sensory tests. Researchers will see how participants respond to sensations such as pinpricks, heat, cold, and pressure. Magnetic resonance imaging (MRI) scan of the brain and/or spine. X-ray of the spine. Ultrasound test of heart function (echocardiogram). Tissues samples (biopsies) collected from the skin, inside of the mouth, and bone marrow. Swabs to collect cells from the mouth, skin, and vagina. Collection of blood, stool, urine, saliva, hair, and fingernail samples. X-rays, MRI, and heart tests will be done only once. Other procedures may be repeated at each visit. All tests and procedures are voluntary. Healthy relatives who enroll will have a baseline visit and then follow-up visits as needed. They will have a physical exam. The inside of their mouth may be swabbed. Samples of blood, stool, urine, and saliva may be taken.

Type: Observational

Start Date: Jul 2026

open study

The purpose of this project is to determine the feasibility and preliminary efficacy of a mental health skill-building and empowerment program (MH-POWER) for college students on the autism spectrum facing stress, anxiety, and depression. The program, grounded in cognitive behavioral therapy (CBT), acceptance and commitment therapy (ACT), and habit formation, will be implemented through weekly sessions and daily practice over 8 weeks. To evaluate the program's preliminary efficacy, we will measure mental health symptoms at baseline, mid-point, post-intervention, and one-month follow-up. Positive outcomes could lead to scalable interventions.

Type: Interventional

Start Date: Jul 2026

open study

The main purpose of this study is to assess the concentrations of nipocalimab (pharmacokinetics [PK]) in the breast milk after administration of a single dose of nipocalimab into the vein, in healthy lactating women.

Type: Interventional

Start Date: Jun 2026

open study

The purpose of this study is to evaluate the efficacy, safety, and tolerability of elecoglipron and dapagliflozin in combination, compared with elecoglipron alone and dapagliflozin alone, in adults with type 2 diabetes mellitus (T2DM) inadequately managed with lifestyle management alone or treated with other background glucose-lowering medication.

Type: Interventional

Start Date: Jul 2026

open study

The purpose of this study is to evaluate the efficacy, safety, and tolerability of elecoglipron alone or in combination with dapagliflozin compared with placebo in adults with type 2 diabetes mellitus (T2DM) inadequately managed with lifestyle management alone or treated with other background glucose-lowering medication.

Type: Interventional

Start Date: Jul 2026

open study

The purpose of this study is to assess the impact of artificial intelligence on proximal caries detection and subsequent treatment decisions of early learners and compare those with outcomes of experienced learners.

Type: Interventional

Start Date: Jul 2026

open study

The study will have two parts: Part A and Part B. In Part A, the goal of the study is to compare the effectiveness of switching to the study drugs GS-3242 plus Lenacapavir (LEN) versus continuing Biktarvy (bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF)), in virologically suppressed people with HIV-1 (PWH) in treatment Group 1, 2 and 3 at Week 35. In Part B the goal of the study is to compare the effectiveness of switching to the study drugs, GS-3242 and LEN versus continuing B/F/TAF in Groups 4 and 3 at Week 26. The primary objective of part A is to evaluate the efficacy of switching to intramuscular (IM) GS-3242 plus IM LEN versus continuing on B/F/TAF PWH who are virologically suppressed in treatment Groups 1, 2, and 3 at Week 35 and Part B is to evaluate the efficacy of switching to IM GS-3242 plus IM LEN versus continuing on B/F/TAF in PWH who are virologically suppressed in Treatment Groups 4 and 3 at Week 26.

Type: Interventional

Start Date: Jun 2026

open study

kTMP, kilohertz transcutaneous magnetic perturbations, is a low intensity transcranial magnetic stimulation technique that will be used in this study to promote arm/hand rehabilitation in patients who have been disabled by stroke.

Type: Interventional

Start Date: Jul 2026

open study

The aim of this study is to evaluate the safety, reactogenicity, and immune response of the different formulations of the investigational RSV/hMPV combination vaccine and investigational hMPV vaccine in younger and older adults.

Type: Interventional

Start Date: Jun 2026

open study