Background: People with alcohol use disorder (AUD) also often have bouts of depression called major depressive episodes (MDEs). People having MDEs have been found to have low levels of a protein called PDE4B in the brain. Researchers want to find out if people with AUD also have low levels of PDE4B. This research may help lead to better treatments for AUD. Objective: To find out (1) if PDE4B levels are lower in people who are withdrawing from AUD and (2) if their PDE4B levels go up after they abstain from alcohol for 3 to 4 weeks. Eligibility: Adults aged 18 to 70 years with AUD. They must be enrolled in protocol 14-AA-0181. Design: Participants enrolled in protocol 14-AA-0181 will stay in the clinic for 3 to 4 weeks for alcohol withdrawal. During this stay, they will have some added procedures for the current study. Within the first week, participants will have a positron emission tomography (PET) scan of the brain. 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 will be injected through the catheter. This tracer binds to PDE4B and makes it easier to see the protein in the brain. For the scan, participants will lie on a table that slides into a doughnut-shaped machine. Participants will have a second PET scan toward the end of their stay in the clinic. Participants may also have a magnetic resonance imaging (MRI) scan of the brain. They will lie on a bed that slides into a tube....

Type: Interventional

Start Date: Mar 2025

open study

Background: Sickle cell disease (SCD) is a genetic disease that causes the body to produce abnormal ( sickled ) red blood cells. SCD can cause anemia and life-threatening complications in the lungs, heart, kidney, and nerves. People with SCD are also at increased risk of forming blood clots in the veins and lungs, but the standard treatments for these clots can cause increased bleeding in people with SCD. Better treatments are needed. Objective: To test a drug (fostamatinib) in people with SCD. Eligibility: People aged 18 to 65 with SCD. Design: Participants will have 6 clinic visits over 12 weeks. Each visit will be 2 to 3 hours. Participants will be screened. They will have a physical exam with blood tests. They will tell the researchers about the medications they take. Fostamatinib is a tablet taken by mouth. Participants will take the drug at home, twice a day, for up to 6 weeks. Participants will have a clinic visit every 2 weeks while they are taking the drug. At each visit they will have a physical exam with blood tests. They will talk about any side effects the drug may be causing. If they are tolerating the drug well after the first 2 weeks, they may begin taking a higher dose. Participants will have a final visit 4 weeks after they stop taking the drug. They will have a physical exam and blood tests; they will be checked for any side effects of the drug.

Type: Interventional

Start Date: Dec 2024

open study

Background: - Li-Fraumeni syndrome (LFS) is a genetic condition that increases the risk for some types of cancer. LFS may lead to cancer of the bone or connective tissue, breast, and brain. It may also increase the risk for certain types of leukemia and other cancers. The only known cause of LFS is a change (called a mutation ) in a gene known as TP53. However, not all people with LFS have a TP53 mutation. Researchers want to study other possible genetic causes of LFS, and factors that may increase or decrease cancer risk in people with the syndrome. Objectives: - To learn more about the types of cancers that occur in individuals with LFS. - To study the role of the TP53 gene in the development of cancer. - To look for other possible genes that cause LFS - To study the effect of LFS diagnosis on families. - To determine if environmental factors or other genes can change a person s cancer risk associated with LFS. Eligibility: - Individuals with a family or personal medical history of cancers consistent with LFS. - Individuals with a family or personal medical history of cancers that does not meet the diagnosis of LFS, but the history is suggestive for LFS (meets the diagnosis for the so-called Li-Fraumeni like syndrome) - Individuals with certain rare cancers - Individuals with a family or personal history of a TP53 gene mutation, with or without related cancer(s). Design: - Participants will fill out a medical history questionnaire and a family history questionnaire. - Blood samples will be collected for DNA and for storage. Cheek cell samples may be collected if blood cannot be obtained for DNA. Participants can choose to have or not have cancer screening with blood tests, imaging studies, and other exams. - Participants will complete questionnaires about their worries about cancer, stress levels, and coping strategies. Diet and physical activity questionnaires will also be given. Other psychological tests may be given as needed. - Participants will be monitored for several years, with regular followup visits to the National Institutes of Health, if indicated. Any changes in health or cancer status will be recorded.

Type: Observational

Start Date: Jan 2012

open study

The purpose of this study is to determine how a ketone ester supplement affects brain function, brain blood flow, and brain metabolism in healthy middle-aged and older adults. Ketones are naturally produced by the body during periods of fasting or carbohydrate restriction and serve as an alternative fuel source for the brain. Researchers are interested in whether increasing blood ketone levels through supplementation can alter brain activity and blood flow in ways that may support healthy brain function. Participants will consume a ketone ester supplement and a placebo in separate study visits. Brain imaging, blood measurements, and cognitive testing will be used to evaluate the effects of each intervention. Findings from this study will help researchers better understand how ketones influence the healthy aging brain and may provide preliminary data for future studies in populations at risk for cognitive decline.

Type: Interventional

Start Date: Jun 2026

open study

The goal of this study is to evaluate the rate of end of study complete cigarette reduction in health adult consumers of cigarettes when given access to a heated tobacco product (HTP). The primary study objective is to evaluate the impact of access to HTP Device 1 or HTP Device 2 and a single stick variant on the rate of final 7-day abstinence from smoking cigarettes among U.S. adult smokers at the end of a 3-month study period.

Type: Interventional

Start Date: Jul 2026

open study

Ocrevus Zunovo implementation, feasibility, acceptability, patient satisfaction, treatment persistence, and impact on MS disease outcomes will be analyzed in this mixed methods study. This study will incorporate clinical data and questionnaire results from MS patients who take Ocrevus Zunovo as well as qualitative interviews with MS patients, family members, and other individuals involved in Ocrevus Zunovo treatment. The purpose of this study is to synthesize implementation strategies that improve patient access to high-efficacy MS therapies in real-world settings.

Type: Observational

Start Date: Jun 2026

open study

This trial will test the effectiveness of a weight loss maintenance intervention designed to help participants respond more adaptively to weight regain. Participants will be randomly assigned to one of two conditions. In one condition, participants will receive brief exercises (e.g., written reflections, videos) sent to through a smartphone app immediately after they regain weight or miss a weigh-in. These exercises will use mindfulness, acceptance, and self-compassion strategies to help participants stay motivated for their long term goals, even when weight regain feels demoralizing. In the comparison condition, participants will receive weekly reminders of standard weight control strategies strategies.

Type: Interventional

Start Date: Jul 2026

open study

The goal of this clinical trial is to evaluate the feasibility of randomizing participants to a "step-up" intervention pathway when they perform <150 minutes of MVPA at the 6-week data collection burst. Participants who performed <150 minutes of MVPA at the 6-week data collection burst will be randomized to either continue with the standard intervention or advance to the step-up intervention. The main questions it aims to answer are: 1. What percentage of participants who are eligible for the intervention phase enroll in the intervention phase? 2. Will participants assigned to the "step-up" intervention pathway demonstrate equal or greater rates of study retention and intervention engagement relative to those assigned to the standard intervention arm? 3. What percentage of the sample is performing >150 minutes accelerometer measured MVPA/week at the intervention mid-point (week 6-data collection burst) and end-of-study (week 12-data collection burst)? 4. Do at least 50% of participants assigned to the "step-up" intervention pathway achieve a clinically meaningful volume of weekly MVPA by 12-weeks follow-up? All participants will: - Be assigned to either the Affect-based exercise prescription or the Effort-based exercise prescription. - Participate in three meetings with the interventionist (an exercise specialist) meant to help them get started increasing weekly exercise. These meetings are the same for all participants. - Be asked to wear an activity monitor and respond to brief surveys for 10 consecutive days at 4 points in time: Baseline, 2weeks, 6weeks, and 12weeks. Some participants (those performing <150 minutes of MVPA at the 6-week data collection burst) will be assigned to the step-up intervention pathway. Participants assigned to the step-up intervention pathway will complete 3 additional follow-up meetings with the interventionist. During these meetings, the interventionist will help participants identify opportunities to be more active, set goals, and problem solve barriers to action.

Type: Interventional

Start Date: Jun 2026

open study

The goal of this clinical trial is to evaluate the feasibility, acceptability, and preliminary effectiveness of the SanaMente peer-led mental health and lifestyle program for rural Latino/a adults with chronic medical conditions and mental health concerns. The main questions it aims to answer are: - Is the SanaMente program feasible and acceptable for rural Latino/a adults with chronic medical conditions and mental health concerns? - Does participation in the SanaMente program improve mental health outcomes (depression, anxiety, and stress), healthy lifestyle behaviors (sleep, physical activity, and nutrition), and overall well-being? This is a single-arm pilot study without comparison group. Participants will: - Participate in the 6-8 week SanaMente peer-led group program. - Complete surveys at baseline, mid-program, and post-program assessing mental health, lifestyle behaviors, overall well-being, and program satisfaction. - Complete an exit survey and have the option to participate in a focus group to provide feedback on the program's usability, acceptability, perceived impact, and suggestions for improvement.

Type: Interventional

Start Date: Mar 2026

open study

This is a Phase 1, first-in-human (FIH), open-label, multicenter study designed to evaluate the safety, tolerability, PK, and preliminary anti-tumor activity of SHY-ONC6 in participants with advanced or metastatic solid tumors who have progressed on or are intolerant to standard therapies. The study will consist of 2 parts: a dose escalation part (Phase 1a) and a dose expansion part (Phase 1b).

Type: Interventional

Start Date: Jun 2026

open study

This study investigates whether tiny molecules called microRNAs (miRNAs), found in special brain-derived "packages" (neural-derived extracellular vesicles, or NDEs) that travel from the brain into the blood, can serve as helpful indicators (biomarkers) for schizophrenia. Currently, doctors diagnose schizophrenia and monitor treatment primarily through clinical interviews, which can be slow and imprecise. This study will work with 80 individuals recently diagnosed with first-episode schizophrenia who are beginning treatment with either aripiprazole or risperidone, along with 80 healthy volunteers. Blood samples will be collected from all participants. For individuals with schizophrenia, blood will be drawn at the beginning of treatment and again after 12 weeks. By comparing patterns of brain-derived miRNAs in the blood of patients versus healthy volunteers, and by observing changes in these miRNAs during treatment, the researchers hope to discover whether these molecules can help diagnose schizophrenia more quickly and predict how well a treatment will work. If successful, this study will provide initial evidence that these miRNAs could become valuable new tools leading to earlier, more accurate diagnoses and more personalized treatment selection.

Type: Interventional

Start Date: Jul 2026

open study

The researchers are doing this study to learn more about factors that may increase the risk of lung cancer in people who have never smoked. This information may help predict which people who have never smoked may be more likely to get lung cancer.

Type: Observational

Start Date: Jun 2026

open study

This study compares p-tau217 concentrations in blood collected via the Tasso device versus standard venipuncture in subjects with and without Alzheimer's disease, including a subset with confirmed amyloid pathology.

Type: Observational

Start Date: Jan 2025

open study

Needle phobia is a barrier for receiving appropriate care during pregnancy and can lead to complications of the mother and fetus that could easily be avoided. Needle phobia can affect routine prenatal care, increase the demand for general anesthesia during c-section, and increase post-op pain. During epidural placement, providers use local anesthetic in various methods to numb the area where the needle will be inserted. Pain from these anesthetic administrations can increase needle phobia and their side effects. One use of local anesthetic is the lidocaine patch, and studies have shown it is effective in reducing pain level in patients [6, Firmani]. The transdermal lidocaine patch may lower the physical pain and mental effects of needle phobia in pregnant women and lower the side effects from that. Although lidocaine patch may take more time to numb the skin, a high number of expecting mothers will not require an epidural for labor analgesia right away. Therefore, administration of lidocaine patch might be an effective alternative. Pregnant women needing epidural placement will be randomized into three groups, the lidocaine patch group, intradermal anesthetic group, or use of both to determine the effectiveness of the lidocaine patch compared to the intradermal administration.

Type: Interventional

Start Date: Jun 2026

open study

Use of a headache journal/calendar in patients who have migraine to ascertain if keeping a headache journal affects the quality of life and the headache burden.

Type: Interventional

Start Date: Jan 2025

open study

The Life Raft Group (LRG) Patient Registry is a structured database that collects comprehensive information about individuals diagnosed with GIST. The purpose of this registry is to facilitate research, improve understanding of the disease, track patient outcomes, and ultimately enhance patient care.

Type: Observational [Patient Registry]

Start Date: Apr 2013

open study

The proposed study will conduct two randomized between-subject experiments among 6,000 adolescents (per each experiment) recruited nationwide to test the effects of audio-visual features of e-cigarette influencer marketing on perceptions of influencer credibility, e-cigarette harm perceptions, appeal, and susceptibility to e-cigarette use. This protocol represent the first experiment.

Type: Interventional

Start Date: Jul 2025

open study

To evaluate the safety and tolerability of low-dose whole brain radiotherapy (WBRT) delivered as an induction course of 0.3 Gy × 10 fractions (3.0 Gy total) followed by 12 months of monthly maintenance LDRT (0.3 Gy × 10 fractions; 3.0 Gy total) in patients with Alzheimer's disease or dementia with inflammatory components

Type: Interventional

Start Date: Jul 2026

open study

The goal of this clinical trial is to determine if NTB-928 can be given safely to adult females with ovarian cancer that has come back (relapsed) or stopped responding to treatment (refractory), how NTB-928 moves through the body, and how the immune system reacts to it. The study will also look for early signs of anti-cancer activity of NTB-928. The main questions the study aims to answer are: - What side effects do participants experience when receiving NTB-928, including side effects that limit how much of it can be safely given? - How is NTB-928 processed by the body at different dose levels? - Does the immune system react to NTB-928 during treatment? - What dose of NTB-928 can be given safely that shows early signs of activity against ovarian cancer?

Type: Interventional

Start Date: Jun 2026

open study

The goal of this clinical trial is to determine the effect of maximal mental effort combined with low-intensity resistance training on strength and neuromuscular function in older adults. The main questions it aims to answer are: - Does low-intensity resistance training in combination with maximal mental effort increase strength more than low intensity resistance training alone? - Does low-intensity resistance training in combination with maximal mental effort improve neuromuscular function more than low intensity resistance training alone? Participants will be randomly assigned to 1 of 3 groups: - Low intensity resistance training - Low intensity resistance training with maximal mental effort - Control Researchers will compare groups to determine differences in changes in strength, neuromuscular function, and body composition.

Type: Interventional

Start Date: Jun 2026

open study

The goal of this study is to learn if phosphate administration works to treat acute pancreatitis in adults presenting to the emergency department at Duke University Hospital. The main questions it aims to answer are: - Does having low phosphate levels increase the risk of acute pancreatitis and can giving phosphate through an IV make the illness less severe? - Is phosphate therapy practical to use, and what is the appropriate dose? - Is this study achievable, and how can the results help design a future randomized controlled trial to assess safety and effectiveness? Participants will: - Receive standard of care or intravenous (IV) phosphate during their hospital stay - Have blood samples collected during admission to monitor phosphorus levels - Complete follow-up assessments after hospital admission to evaluate how severe the illness is and the effects of phosphate supplementation

Type: Interventional

Start Date: Jul 2026

open study

This trial is a randomized, double-blind, placebo-controlled study evaluating the safety and preliminary efficacy of inhaled Nintedanib Dry Powder Inhalation (DPI) in adults with idiopathic pulmonary fibrosis (IPF). Participants are randomized to receive either 2 mg QID, 4 mg BID, or matching placebo for 12 weeks, followed by a 24-week open-label extension in which all participants receive active treatment. The primary focus is on safety-particularly bronchospasm events, lung function changes (FEV1, FEV1/FVC), and adverse event rates and assessing the effectiveness of nintedanib DPI in treating IPF.

Type: Interventional

Start Date: Jun 2026

open study

The purpose of the trial is to evaluate the pharmacokinetics, safety, and tolerability of TEV-56286 at different doses. The main objective is to describe how TEV-56286 is absorbed, distributed, and removed from the body (the pharmacokinetics) following administration of TEV-56286 in single doses of increasing amounts and multiple doses in healthy participants. A secondary objective is to assess the safety of TEV-56286 and how well it is tolerated. The estimated duration for participants in Part 1 with Single Ascending Dose is approximately 58 days; including up to 45 days of screening, a 4-day in-clinic period, and follow-up 8+/-1 days post discharge from the clinical unit. The estimated duration for participants in Part 2 with Multiple Dose is approximately 64 days; including 45 days of screening, a 10-day in-clinic period, and follow-up 8+/-1 days post discharge from the clinical unit.

Type: Interventional

Start Date: Jun 2026

open study

This is a research study to better understand how long-acting cabotegravir (CAB-LA) works to prevent HIV in people. This study will also evaluate the impact of endogenous and therapeutic hormones on CAB-LA pharmacology. The investigators will also evaluate if participants experience any medical problems when taking CAB-LA.

Type: Interventional

Start Date: Jul 2026

open study

The study is centered on helping parents answer and meet the sexuality-specific questions and needs of gay or bisexual males. This study seeks to test the efficacy of Parents ASSIST as a parent-child sexuality communication intervention that educates and trains parents to be purveyors of inclusive health information as gay or bisexual sons come of age at home.

Type: Interventional

Start Date: May 2026

open study