This study adopts a strategy that has arisen from basic neuroscience research on facilitating adaptive brain plasticity and applies this to rehabilitation to improve functional recovery in peripheral nervous system injuries (including hand transplantation, hand replantation, and surgically repaired upper extremity nerve injuries). The technique involves combining behavioral training with transcranial direct current stimulation (tDCS)-a non-invasive form of brain stimulation capable of facilitating adaptive changes in brain organization.

Type: Interventional

Start Date: Aug 2018

open study

It is believed that targeted SERCA2a enzyme replacement in HFrEF patients will correct defective intracellular Ca2+ hemostasis, resulting in improved cardiac contractile function and energetics which will, in turn, translate to improved clinical outcomes. Additionally, it is hypothesized that correcting SERCA2a dysfunction will also improve coronary blood flow through correction of the impaired endothelium-dependent nitric oxide-mediated vasodilatation observed in heart failure.

Type: Interventional

Start Date: Sep 2021

open study

The primary objective is to assess the safety and tolerability of TAB004 as monotherapy and in combination with toripalimab in subjects with selected advanced solid malignancies, including lymphoma, and to evaluate the recommended Phase 2 dose. The secondary objectives are to: 1) describe the pharmacokinetic (PK) profile of TAB004 monotherapy and in combination with toripalimab and to describe the PK profile of toripalimab when administered with TAB004, 2) evaluate antitumor activity of TAB004 monotherapy and in combination with toripalimab; and 3) determine the immunogenicity of TAB004 monotherapy and in combination with toripalimab and to determine the immunogenicity of toripalimab when administered with TAB004. The exploratory objectives are to: 1) evaluate pharmacodynamic effects of TAB004 on its target receptor BTLA, as well as effects on the immune system; 2) evaluate biomarkers that may correlate with activity of TAB004 as monotherapy and in combination with toripalimab; 3) evaluate the utility of BTLA ligand, herpesvirus-entry mediator (HVEM), and additional exploratory biomarkers that could aid in selection of appropriate subjects for TAB004 monotherapy and in combination with toripalimab.

Type: Interventional

Start Date: Oct 2019

open study

Enroll-HD is a longitudinal, observational, multinational study that integrates two former Huntington's disease (HD) registries-REGISTRY in Europe, and COHORT in North America and Australasia-while also expanding to include sites in Latin America. More than 30,000 participants have now enrolled into the study. With annual assessments and no end date, Enroll-HD has built a large and rich database of longitudinal clinical data and biospecimens that form the basis for studies developing tools and biomarkers for progression and prognosis, identifying clinically-relevant phenotypic characteristics, and establishing clearly defined endpoints for interventional studies. Periodic cuts of the database are now available to any interested researcher to use in their research - visit www.enroll-hd.org/for-researchers/access-data/ to learn more.

Type: Observational [Patient Registry]

Start Date: Jul 2012

open study

This project will assess how depression, preclinical AD, and antidepressants affect driving behavior in cognitively normal older adults (65 years).

Type: Observational

Start Date: Jun 2021

open study

This project will be a multi-center, prospective longitudinal cohort for all patients undergoing primary shoulder instability surgery, excluding isolated SLAP repairs. We will be looking for risk factors for recurrent instability, revision surgery, and poor outcomes. Patients will be asked to complete the RAND-36, ASES, Shoulder Activity, EQ-5D and WOSI outcome measures, as well as demographic and socioeconomic information. Surgeons will complete a form after surgery with information on radiographic findings, physical exam, surgical findings, and the repair. Patients will wear a sling post-operatively, and follow standardized rehabilitation protocols, including physical therapy. Patients will be sent outcome questionnaires at 2, 6, 10, and 20 years after surgery.

Type: Observational [Patient Registry]

Start Date: Aug 2012

open study

The object of this study is to longitudinally collect clinical outcomes of patients receiving deep brain stimulation for movement disorders with the objective of making retrospective comparisons and tracking of risks, benefits, and complications.

Type: Observational

Start Date: Jan 2011

open study

Without an explanation for severe and sometimes life-threatening symptoms, patients and their families are left in a state of unknown. Many individuals find themselves being passed from physician to physician, undergoing countless and often repetitive tests in the hopes of finding answers and insight about what the future may hold. This long and arduous journey to find a diagnosis does not end for many patients- the Office of Rare Diseases Research (ORDR) notes that 6% of individuals seeking their assistance have an undiagnosed disorder. In 2008, the National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) was established with the goal of providing care and answers for these individuals with mysterious conditions who have long eluded diagnosis. The NIH UDP is a joint venture of the NIH ORDR, the National Human Genome Research Institute Intramural Research Program (NHGRI-IRP), and the NIH Clinical Research Center (CRC) (1-3). The goals of the NIH UDP are to: (1) provide answers for patients with undiagnosed diseases; (2) generate new knowledge about disease mechanisms; (3) assess the application of new approaches to phenotyping and the use of genomic technologies; and (4) identify potential therapeutic targets, if possible. To date, the UDP has evaluated 3300 medical records and admitted 750 individuals with rare and undiagnosed conditions to the NIH Clinical Center. The NIH UDP has identified more than 70 rare disease diagnoses and several new conditions. The success of the NIH UDP prompted the NIH Common Fund to support the establishment of a network of medical research centers, the Undiagnosed Diseases Network (UDN), for fiscal years 2013-2020. The clinical sites will perform extensive phenotyping, genetic analyses, and functional studies of potential disease-causing variants. The testing performed on patients involves medically indicated studies intended to help reach a diagnosis, as well as research investigations that include a skin biopsy, blood draws, and DNA analysis. In addition, the UDN will further the goals of the UDP by permitting the sharing of personally identifiable phenotypic and genotypic information within the network. By sharing participant information and encouraging collaboration, the UDN hopes to improve the understanding of rare conditions and advance the diagnostic process and care for individuals with undiagnosed diseases.

Type: Observational

Start Date: Sep 2015

open study

Treatment for relapsed/refractory multiple myeloma continues to evolve with the approval of highly effective anti-BCMA CAR T therapies in recent years. However, despite the high prevalence of renal insufficiency in this population, pivotal clinical trials have excluded patients with impaired renal function, leading to an urgent, unmet clinical need to develop safe and effective lymphodepleting regimens prior to CAR T administration for this population. In addition, renal insufficiency is linked to poor disease-related outcomes and is highly associated with several underserved populations. This study is testing the hypotheses that: 1. low-dose total body irradiation (TBI) in combination with cyclophosphamide (Cy) as lymphodepletion prior to administration of cilta-cel will be safe and tolerable in patients with multiple myeloma who have impaired renal function 2. low-dose TBI-Cy as lymphodepletion prior to cilta-cel will result in comparable CAR T expansion/persistence and disease response rates as those seen with standard lymphodepleting chemotherapy (fludarabine / cyclophosphamide).

Type: Interventional

Start Date: Dec 2024

open study

AJX-101 is a first-in-human (FIH), phase 1, non-randomized, multi-center, open-label clinical trial designed to investigate the safety, tolerability, pharmacokinetics (PK), clinical activity and changes in biomarkers of an orally administered type II JAK2 inhibitor, AJ1-11095, in subjects with primary or secondary myelofibrosis previously treated with at least one type I JAK2 inhibitor.

Type: Interventional

Start Date: Oct 2024

open study

Spatially fractionated radiotherapy (SFRT or GRID) addresses some limitations of traditional stereotactic body radiation therapy by relying on beam collimation to create high-dose "peaks" and intervening low-dose "valleys" throughout the target volume. Standard palliative radiotherapy regimens provide limited durability of response, and there are challenges with delivery to large tumors or in previously irradiated fields. In this study, Proton GRID radiotherapy will be used to deliver three-fraction palliative radiotherapy to patients with tumors needing palliative radiation. The safety and efficacy of this approach will be assessed. It is hypothesized that GRID is highly effective, immunogenic, and associated with low rates of toxicity.

Type: Interventional

Start Date: May 2023

open study

This phase I/II trial studies the side effects and best dose of temozolomide and M1774 and how well they works in treating patients with cancer that has spread from where it first started (primary site) to other places in the body (metastatic) and may have spread to nearby tissue, lymph nodes, or distant parts of the body (advanced). Temozolomide is in a class of medications called alkylating agents. It works by damaging the cell's deoxyribonucleic acid (DNA) and may kill tumor cells and slow down or stop tumor growth. M1774 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Adding M1774 to temozolomide may shrink or stabilize cancer for longer than temozolomide alone.

Type: Interventional

Start Date: Sep 2023

open study

In this first-in human, phase I/IIa study, the safety and efficacy of [212Pb]VMT01, an alpha-particle emitting therapeutic agent targeted to melanocortin sub-type 1 receptor (MC1R) is being evaluated as a monotherapy and in combination with nivolumab in subjects with unresectable and metastatic melanoma.

Type: Interventional

Start Date: Jun 2023

open study

This is a multicenter trial to establish the efficacy of cooling and the optimal duration of induced hypothermia for neuroprotection in pediatric comatose survivors of cardiac arrest. The study team hypothesizes that longer durations of cooling may improve either the proportion of children that attain a good neurobehavioral recovery or may result in better recovery among the proportion already categorized as having a good outcome.

Type: Interventional

Start Date: Aug 2022

open study

This is a 3-part study. The purpose of Part 1 of the study is to evaluate the efficacy, safety, and pharmacokinetic (PK) characteristics of safusidenib in participants with recurrent/progressive IDH1-mutant World Health Organization (WHO) Grade 2 or Grade 3 glioma. The purpose of Part 2 will be to evaluate the efficacy of maintenance safusidenib treatment versus placebo in IDH1-mutant Grade 2 or Grade 3 astrocytoma with high-risk features or IDH1-mutant Grade 4 astrocytoma, following standard-of-care radiation or chemoradiation and adjuvant temozolomide. Part 2 will be randomized, double-blind, and placebo-controlled. The purpose of Part 3 will be to evaluate the efficacy of safusidenib in participants with residual or recurrent IDH1-mutant Grade 3 oligodendroglioma who have received surgery as their only treatment. Part 3 will be an open-label single-arm cohort and will enroll participants concurrently with Part 2.

Type: Interventional

Start Date: Jun 2023

open study

This phase II trial studies the good and bad effects of the combination of drugs called cabozantinib and nivolumab in treating patients with melanoma or squamous cell head and neck cancer that may have spread from where it first started to nearby tissue, lymph nodes, or distant parts of the body (advanced). Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. This trial may help doctors determine how quickly patients can be divided into groups based on biomarkers in their tumors. A biomarker is a biological molecule found in the blood, other body fluids, or in tissues that is a sign of a normal or abnormal process or a sign of a condition or disease. A biomarker may be used to see how well the body responds to a treatment for a disease or condition. The two biomarkers that this trial is studying are "tumor mutational burden" and "tumor inflammation signature." Another purpose of this trial is to help doctors learn if cabozantinib and nivolumab shrink or stabilize the cancer, and whether patients respond differently to the combination depending on the status of the biomarkers.

Type: Interventional

Start Date: Dec 2022

open study

Demonstrate the relationship between DD-cfDNA levels and HLA antibodies in blood, and the Molecular Microscope® (MMDx) Diagnostic System results in indication biopsies.

Type: Observational

Start Date: Dec 2019

open study

The purpose of this research study is to learn more about the outcomes and early and late side effects of treating early stage prostate cancer with high dose rate brachytherapy.

Type: Interventional

Start Date: Feb 2018

open study

This project will compare two training approaches for US Preventive Services Task Force recommended obesity care in Federally Qualified Health Centers (FQHC) across four aims. Aim 1 compares patient-level effectiveness [i.e., patient relative weight change and the proportion of patients who achieve clinically significant weight loss]. Aim 2 compares reach (patient treatment utilization). Aim 3 compares primary care provider (PCP) referrals to USPSTF-recommended care at 12 (adoption) and 24 months (maintenance) and short- and long-term changes in provider obesity care competencies . Aim 4 compares implementation and service costs.

Type: Interventional

Start Date: Jul 2025

open study

FORTITUDE-HCM is a global, multicenter, double-blind, parallel-group, placebo-controlled Phase 2b study that will assess the efficacy and safety of ninerafaxstat compared to placebo on top of Standard of Care in patients with symptomatic nHCM

Type: Interventional

Start Date: Oct 2025

open study

This study is designed to demonstrate the efficacy and assess safety and tolerability of oral daily alpelisib in participants with PIK3CA-related overgrowth spectrum (PROS).

Type: Interventional

Start Date: Oct 2025

open study

Researchers are looking for new ways to treat types of breast cancer that are both: - High-risk, which means the cancer may have a higher chance of getting worse or coming back after treatment - Early-stage, which means the cancer is in the breast or the lymph nodes around the breast The 2 types of breast cancer in this study are triple-negative breast cancer (TNBC) and hormone receptor (HR)-low positive/human epidermal growth factor receptor-2 (HER2) negative breast cancer. These cancers have zero or a low amount of a protein called HER2 and other proteins that attach to the hormones estrogen or progesterone. Sacituzumab tirumotecan (also known as sac-TMT or MK-2870), the study medicine, is a type of targeted therapy. A targeted therapy is a treatment that works to control how specific types of cancer cells grow and spread. The main goals of this study are to learn if people who receive sac-TMT, pembrolizumab, and chemotherapy: - Have fewer cancer cells found in the tumors and lymph nodes removed during surgery compared to those who receive only pembrolizumab and chemotherapy - Live longer without the cancer growing, spreading, or coming back compared to people who receive only pembrolizumab with chemotherapy

Type: Interventional

Start Date: Jun 2025

open study

This phase II trial compares the effect of giving cabozantinib with or without cemiplimab in patients with adrenocortical cancer that has spread to nearby tissue or lymph nodes (locally advanced), and that cannot be removed by surgery (unresectable) or that has come back after a period of improvement (recurrent) or that has spread from where it first started (primary site) to other places in the body (metastatic). Cabozantinib is in a class of medications called tyrosine kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply, which may help keep cancer cells from growing. Immunotherapy with monoclonal antibodies, such as cemiplimab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving cabozantinib with cemiplimab may kill more tumor cells in patients with locally advanced unresectable or recurrent/metastatic adrenocortical cancer.

Type: Interventional

Start Date: Feb 2026

open study

This phase III trial compares 6 months of human epidermal growth factor receptor 2 (HER2)-targeted therapy to 12 months of HER2-targeted therapy for the treatment of HER2-positive (+) breast cancer in patients that had a pathologic complete response (pCR) after preoperative (neoadjuvant) chemotherapy with trastuzumab. Trastuzumab and pertuzumab are monoclonal antibodies and forms of targeted therapy that attach to a receptor protein called HER2. HER2 is found on some cancer cells. When trastuzumab or pertuzumab attach to HER2, the signals that tell the cells to grow are blocked and the tumor cell may be marked for destruction by the body's immune system. Giving 6 months of HER2-targeted therapy may work better than giving 12 months for the treatment of HER2+ breast cancer in patients that had a pCR after neoadjuvant chemotherapy with trastuzumab.

Type: Interventional

Start Date: Sep 2025

open study

Characteristics and clinical course of disease In participants with cardiomyopathy associated with Friedreich Ataxia (CLARITY-FA)

Type: Observational

Start Date: Sep 2025

open study