The purpose of this study is to evaluate the efficacy, safety, and tolerability of elecoglipron, compared with placebo in adults with type 2 diabetes mellitus (T2DM) and impaired renal function, who are or will be on a background of sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin 10 mg as per guideline directed medical therapy (GDMT) for chronic kidney disease (CKD). Additionally, participants are on other glucose-lowering medication(s).

Type: Interventional

Start Date: Jul 2026

open study

The purpose of this Medical Access Program (also referred to as an Expanded Access Program in the USA) is to provide access to I-DXd for eligible patients with extensive-stage small cell lung cancer (ES-SCLC) after two or more prior lines of treatment (including at least one platinum-based regimen), and for eligible patients who have no suitable treatment options and are not able to enter a clinical study.

Type: Expanded Access

open study

This is a prospective, single-arm phase 2 pilot study to assess the response rate of IDH1 mutated relapsed/refractory acute myeloid leukemia (AML) patients who receive olutasidenib after progressing on venetoclax based regimens. Each cycle will last for 28 days. Patients will receive olutasidenib 150 mg orally twice daily Day 1 through Day 28. After 3 cycles of olutasidenib, azacitidine 75 mg/m2 given on Day 1 through Day 7 may be added at the discretion of the treating investigator if the patient has not achieved a complete remission. Subjects with at least a PR after 6 cycles of treatment will continue treatment as previously described. Subjects without at least a partial response (PR) after 6 cycles of treatment will move to long term follow up.

Type: Interventional

Start Date: Sep 2026

open study

This basket trial will enroll prepubertal children and adolescents with clinically diagnosed and genetically confirmed (if applicable) TS, SHOX-D, SGA, or ISS between ages of ≥2 and <18 years with open growth plates. The purpose of the study is to see how well treatment with once-weekly lonapegsomatropin works compared to treatment with daily somatropin. Approximately 186 participants will be distributed equally (1:1), to receive either lonapegsomatropin for 2 years or somatropin for 1 year followed by lonapegsomatropin for 1 year. This trial will be conducted in the United States, France, Germany, Italy, Romania, Spain and South Korea.

Type: Interventional

Start Date: Dec 2025

open study

The purpose of this study is to evaluate the efficacy, safety, and tolerability of povetacicept in participants with primary membranous nephropathy (pMN).

Type: Interventional

Start Date: Sep 2025

open study

This study will evaluate the safety, efficacy, optimal dose, and pharmacokinetics (PK) of BNT326 as monotherapy (Part 1) and as combination treatment with immunotherapeutic agents (Part 2) in participants with histologically or cytologically confirmed solid tumors that are advanced (i.e., either metastatic or recurrent tumors with no further definitive treatment possible) and/or have relapsed/progressed after prior therapy.

Type: Interventional

Start Date: Aug 2025

open study

The purpose of this study is to determine how circulating tumor DNA (ctDNA), a sign of minimal residual disease (MRD), is detectable after surgery in patients with early HR+/HER2- breast cancer that has spread to 1-3 lymph nodes. Researchers aim to understand if ctDNA detection can identify patients at higher risk of recurrence and guide better treatment decisions. A key aspect is the inclusion of a dedicated cohort of African American/Black women, a group underrepresented in molecular residual disease (MRD) research despite experiencing more aggressive breast cancers. This study will correlate ctDNA results with treatment patterns (radiotherapy, systemic therapy) and outcomes (recurrence-free and overall survival) in both non-African American and African American participants.

Type: Interventional

Start Date: Aug 2025

open study

The overall objective of this 14-month randomized crossover study is to seek evidence demonstrating that daily consumption of peanuts and peanut products improve cardiometabolic, cognitive, and intestinal health in a racially diverse prediabetes population.

Type: Interventional

Start Date: Mar 2025

open study

This Phase 1, multicenter, open-label, dose escalation and dose optimization study is designed to assess the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of AUTX-703 administered orally in subjects with advanced hematologic malignancies.

Type: Interventional

Start Date: May 2025

open study

This is a single arm phase II study of pemigatinib and durvalumab combination in patients with FGFR-2 fusion or rearrangement positive intrahepatic cholangiocarcinoma. Each cycle will be 3 weeks. Pemigatinib is administered at 13.5 mg orally daily 2 weeks on and 1 week off. Durvalumab is administered at 1500 mg intravenously once every 3 weeks. Subjects will require a visit with appropriate laboratory work prior to the start of each cycle. Disease assessment will occur every 9 weeks. Subjects will continue treatment until progression per RECIST 1.1, toxicity or subject/physician decision. A maximum of 24 months (about 35 cycles) of pemigatinib and durvalumab treatment from Cycle 1 Day 1 is allowed.

Type: Interventional

Start Date: Jan 2026

open study

This pilot study will enroll 20 patients with septic shock and require emergent vasopressor support in the emergency department (ED). The primary objective of the study is to determine the feasibility of early peripheral administration of angiotensin II for treatment of septic shock in the ED

Type: Interventional

Start Date: Apr 2025

open study

The purpose of this study is to find out whether a medicine called spesolimab helps people with pyoderma gangrenosum (PG). The main aim is to see whether spesolimab leads to closure of PG ulcers. This study is open to adults with ulcerative PG with at least 1 ulcer that measures between 5 cm^2 to 80 cm^2 in size. This study has 2 parts. In Part 1, participants are put into groups randomly, which means by chance. 1 group gets spesolimab and the other group gets placebo. Placebo infusions look like spesolimab infusions, but do not contain any medicine. Every participant has a 2 in 3 chance of getting spesolimab. For the first 8 weeks, participants also take corticosteroid medicine by mouth. In Part 2, participants are put into groups again. Participants without open ulcers have an equal chance of getting spesolimab or placebo. Participants with open skin ulcers will get spesolimab. In both parts, participants receive spesolimab or placebo as an infusion into a vein every 4 weeks. Participants are in the study for about 1.5 years. During this time, they visit the study site 20 times. At study visits, doctors check the participant's skin for signs of PG. The doctors also regularly check participants' health and take note of any unwanted effects. The results of the groups are compared to see whether the treatment works.

Type: Interventional

Start Date: Feb 2025

open study

This is a phase 1/2, multicenter, open-label umbrella platform study that will evaluate the safety and tolerability of investigational agents with pembrolizumab and fluoropyrimidine chemotherapy for the first-line (1L) treatment of participants with locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric, gastroesophageal junction, or esophageal adenocarcinoma. This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to evaluate the safety and tolerability, and to establish a recommended Phase 2 dose (RP2D) for investigational agents in combination with chemotherapy and immunotherapy. There is no formal hypothesis in this study.

Type: Interventional

Start Date: Sep 2024

open study

The goal of this clinical trial is to see if a mobile phone app can deliver depression treatment to African Americans who are depressed. The main question it aims to answer is if this treatment is effective in reducing symptoms of depression. Participants will attend six 90-minute weekly classes via an app on their phone, and will be asked to complete surveys every week. Participants can expect to be in the study for four months.

Type: Interventional

Start Date: Sep 2026

open study

This is a multicenter randomized, open label study to evaluate overall survival with the Bria-IMT regimen in combination with Checkpoint Inhibitor [Retifanlimab], versus Treatment of Patients'/Physicians' Choice (TPC) in advanced metastatic or locally recurrent breast cancer (aMBC) patients with no approved alternative therapies available.

Type: Interventional

Start Date: Dec 2023

open study

The purpose of this study is to evaluate the efficacy and safety of adjuvant autogene cevumeran plus atezolizumab and modified leucovorin, 5-fluorouracil (5-FU), irinotecan, and oxaliplatin (mFOLFIRINOX) versus mFOLFIRINOX alone in participants with resected pancreatic ductal adenocarcinoma (PDAC) who have not received prior systemic anti-cancer treatment for PDAC and have no evidence of disease after surgery.

Type: Interventional

Start Date: Oct 2023

open study

This Phase III Trial will determine whether adjuvant chemotherapy (ACT) added to ovarian function suppression (OFS) plus endocrine therapy (ET) is superior to OFS plus ET in improving invasive breast cancer-free survival (IBCFS) among premenopausal, early- stage breast cancer (EBC) patients with estrogen receptor (ER)-positive, HER2-negative tumors and 21-gene recurrence score (RS) between 16-25 (for pN0 patients) and 0-25 (for pN1 patients).

Type: Interventional

Start Date: Oct 2023

open study

This is a Phase 1/2, multicenter, randomized, open-label umbrella platform study to evaluate the safety and efficacy of investigational agents with or without pembrolizumab and/or chemotherapy, for the treatment of participants with second line (2L) esophageal squamous cell carcinoma (ESCC) who have previously been exposed to PD-1/PD-L1 based treatment.

Type: Interventional

Start Date: May 2023

open study

This phase II trial studies how well vismodegib, focal adhesion kinase (FAK) inhibitor GSK2256098, and capivasertib work in treating patients with meningioma that is growing, spreading, or getting worse (progressive). Vismodegib, FAK inhibitor GSK2256098, capivasertib, and abemaciclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Type: Interventional

Start Date: Sep 2015

open study

Background: Chronic graft-versus-host disease (cGVHD) is an immune system disorder that can occur in people who have had a stem cell transplant. cGVHD can affect multiple organs and increase risk of disability and death. New treatments are needed to treat cGVHD after stem cell transplant. Objective: To test a drug (pacritinib) in people with moderate or severe cGVHD that has not responded to previous treatment. Eligibility: People aged 18 years and older with moderate or severe cGVHD that has not responded to 2 or more lines of previous treatment. Design: Participants will be screened. They will have blood and urine tests. They will have tests of their heart and lung function. They may also have a CT scan. Some may have other specialized tests. Participants will take the study drug at home every day. Pacritinib is a capsule taken by mouth. The study doctor will determine the dosage and schedule. Participants will keep a medication diary. They will record the date and time of each drug dose and any missed doses. Participants will visit the clinic every 2 weeks for the first 4 months. Then they will visit the clinic once every 4 weeks. They will have blood and urine tests. During some visits, other screening tests will be repeated, and participants will fill out questionnaires about their quality of life. Photographs may be taken of skin rashes and joints affected by cGVHD. Participants will give saliva samples. Optional biopsies may be taken of the skin and mouth. Participants will take pacritinib for 6 to 12 months if no side effects develop. Follow-up visits will continue for up to 2 years. ...

Type: Interventional

Start Date: Mar 2023

open study

Background: Current techniques used to measure the health and function of a person s nerves and muscles are generally effective, but they do have limits. Researchers are looking for ways to improve the ability to observe nerves and muscles and how they function in this natural history protocol. Objective: To study the use of ultrasound (sound waves) to learn more about nerves and muscles. Eligibility: Healthy adults, aged 18 and older, with no history of stroke, nerve or muscular disorders, or spine surgery are also needed. A smaller population of adults aged 18 and older who have a neuromuscular disorder or show symptoms of nerve or muscle disorder will also be evaluated. Design: Participants will be screened with a medical record review. Participants will have up to 5 outpatient clinic visits. Most participants will have 1 or 2 visits. Visits will last for less than 3-4 hours each. During each visit, participants will give a brief medical history and have a physical exam. Participants will have ultrasounds to get pictures and measurements of their nerves and muscles. Gel will be applied to their skin. A probe will be placed on the skin surface. Sound waves sent through the probe will be used to create pictures. Participants may have nerve conduction studies. Wires will be taped to the skin surface near a muscle or nerve in the arm or leg. The nerve will be stimulated with a small electric current that feels like a rubber band flick. The response will be recorded through the wires.

Type: Observational

Start Date: Apr 2022

open study

Background: Impulsivity is acting 'without thinking.' Compulsivity is being overly inflexible. People vary in how impulsive or compulsive they are. Extreme versions of these behaviors play a role in mental disorders. Researchers want to study changes in the brain to learn more about these behaviors. Differences in genes may also play a role. Objective: To learn about genetic & brain features that explain why levels of impulsivity and compulsivity vary across people. Eligibility: People ages 6 - 80 Design: Participants will be screened with a medical history and medical record review. Participants will talk about their mental and behavioral development. They may discuss topics like drug use and sexual activity. They will complete surveys about their compulsivity and impulsivity. Parents of child participants may also complete these surveys. Participants may take memory, attention, and thinking tests. They may give blood or saliva samples for gene studies and they may give blood to make induced pluripotent stem cells. Participants may have their face and irises photographs taken. Participants may have a magnetic resonance imaging scan. It will take pictures of their brain. The scanner is shaped like a cylinder. Participants will lie on a table that slides in and out of the scanner. A coil will be placed over their head. They will lie still, watch a movie, and play a game. Participants may ask family members to join the study. Researchers are particularly interested in recruiting twin pairs to the study. Participants under age 25 may repeat these tests every 1-2 years until they turn 25 or until the study ends. For those over age 25, participation will last less than 1 month.

Type: Observational

Start Date: Sep 2022

open study

Background: - Noncirrhotic Portal Hypertension (NCPH) is caused by liver diseases that increase pressure in the blood vessels of the liver. It seems to start slowly and not have many warning signs. Many people may not even know that they have a liver disease. There are no specific treatments for NCPH. Objectives: - To learn more about how NCPH develops over time. Eligibility: - People age 12 and older who have NCPH or are at risk for getting it. In the past year, they cannot have had other types of liver disease that typically result in cirrhosis, liver cancer, or active substance abuse. Design: - Participants will have 2 screening visits. - Visit 1: to see if they have or may develop NCPH. - Medical history - Physical exam - Urine and stool studies - Abdominal ultrasound - Fibroscan. Sound waves measure liver stiffness. <TAB>- Visit 2: - Blood tests - Abdominal MRI - Echocardiogram - Questionnaire - Liver blood vessel pressure (hepatic venous portal gradient (HVPG)) measurement. This is done with a small tube inserted in a neck vein. - They may have a liver biopsy. - All participants will visit the clinic every 6 months for a history, physical exam, and blood tests. They will also repeat some of the screening tests yearly. - Participants with NCPH will also have: - Upper endoscopy test. A tube inserted in the mouth goes through the esophagus and stomach. - At least every 2 years: Esophagogastroduodenoscopy. - At least every 4 years: testing including HVPG measurements and liver biopsy. - Participants without NCPH will also have: - Liver biopsy and HVPG measurements to see if they have NCPH. - Every 2 years: abdominal MRI and stool studies. - The study will last indefinitely.

Type: Observational

Start Date: Jul 2015

open study

This study will collect fluid and tissue specimens from the lungs and nose of healthy people and people with a history of lung infections. The specimens will be examined for differences between the two groups that may be associated with susceptibility to certain infections. Healthy normal volunteers and people with a history of lung infections between 18 and 75 years of age who are followed at NIH may be eligible for this study. Participants undergo the following procedures: Medical history and physical examination. Blood and urine tests. Electrocardiogram (ECG) and chest x-ray. Treadmill exercise stress test (for people over 45 years old with a history of chest pain or ECG abnormalities). Bronchoscopy: The subject s nose and throat are numbed with lidocaine and a sedative is given for comfort. A thin flexible tube called a bronchoscope is advanced through the nose or mouth into the lung airways to examine the airways carefully. Fluid collection during the bronchoscopy using one of the following methods: - Bronchoalveolar lavage: Salt water is injected through the bronchoscope into the lung and immediately suctioned out, washing off cells lining the airways. - Bronchial brushings: A brush-tipped wire enclosed in a sheath is passed through the bronchoscope and a small area of the airway tissue is gently brushed. The brush is withdrawn with some tissue adhering to it. - Endobronchial biopsies: Small pinchers on a wire are passed through the bronchoscope and about 1 to 2 millimeters of tissue is removed. - Nasal scrape: A small device is used to scrape along the inside of the nose to collect some cells. - Sputum induction - Exhaled breath condensate to obtain specimens for in vitro investigations and comparisons of both the cellular and acellular components. - Nasal nitric oxide production - Nasal potential difference - Exhaled aerosol mask sample collection - Cough aerosol collection - Exhaled particle collection - Lung Clearance Index (LCI)

Type: Observational

Start Date: Aug 2007

open study

Background: Cortisol is a hormone in the blood. Cortisol levels normally go down at night and up in the morning. Mild autonomous cortisol secretion (MACS) is a disease in which the body makes too much cortisol. MACS can cause high blood pressure, diabetes, and/or weight gain. Researchers think these problems may be caused by higher cortisol levels at night. Objective: To compare daily cortisol levels in people with MACS with those in healthy people. Also, to test a drug (ketoconazole) that may help lower cortisol levels in people with MACS. Eligibility: People aged 18 years and older with MACS. Healthy volunteers are also needed. Design: Participants with MACS will have a 2-night stay in the hospital. Day 1: A thin tube called a catheter will be inserted into a vein in the arm. Blood will be collected through the catheter every 2 hours starting at 8 PM. Participants will begin a 24-hour urine collection. Saliva will be collected every 6 hours for 24 hours. Day 2: Participants will take 2 tablets of the study drug ketoconazole with their evening meal. Blood will be collected via the catheter at regular intervals throughout the night. Day 3: Participants will leave the hospital in the morning. Healthy volunteers will be screened with a physical exam and blood tests. They will be tested to make sure they do not have MACS. To do this, they will take a drug (dexamethasone) at 11 PM on a day they choose; then they will return the next morning for a blood test. Healthy volunteers will have a 1-night stay in the hospital. They will have blood, urine, and saliva collected for 24 hours.

Type: Interventional

Start Date: Jul 2026

open study