All Clinical Trials

This study will examine the symptoms, course of disease and treatment of non-tuberculous mycobacterial (NTM) infections, as well as the genetics involved in these infections. Patients with NTM have recurrent lung infections and sometimes infections of the skin and other organs as well. They may also have curvature of the spine, barrel chest, and heart valve weakness. The study will compare the features of NTM with those of Job syndrome and cystic fibrosis, other diseases involving recurrent infections of the lungs and possibly other organs. Patients with diagnosed or suspected non-tuberculous mycobacterial infection, cystic fibrosis or Job syndrome may be eligible for this study. All participants will have a medical and family history, blood and urine tests, imaging studies that may include X-rays, computed tomography (CT) or magnetic resonance imaging (MRI) scans, and DNA and other genetic studies. In addition, all patients with Job syndrome and cystic fibrosis, and patients with NTM who have lung disease undergo the following procedures: * Scoliosis survey X-rays of the spine to look for curvature or other abnormalities of the spinal column * Echocardiography imaging test that uses sound waves to examine the heart chambers and valves * Electrocardiogram measurement of the electrical activity of the heart * Pulmonary function tests breathing tests to measure how much air the patient can move into and out of the lungs * Body measurements measurements of height, weight, arm span, finger length, etc. * Joint function assessment of joint mobility using different maneuvers to test flexibility of joints and ligaments * Examination of physical features that might be associated with NTM, such as high arched palate of the mouth, flat feet, or certain skin features * Dermatology (skin) examination for reactive skin conditions or other skin problems and possibly a skin biopsy (surgical removal of a small skin tissue sample for microscopic examination) * Interview with genetics specialist These tests may require several days to complete. Patients with NTM will also be examined by a cystic fibrosis specialist and may have a sweat test. In addition, NTM patients will be asked to return to NIH every year for 5 years for follow-up tests, if medically indicated, including CT of the chest, scoliosis survey and examination by other specialists. ... Read Less

Background: * Chromatin is is the structural building block of a chromosome. It is found inside the nucleus of the cell and consists of a complex of DNA and protein. * Cancers of the lung, pleura (lung lining) and esophagus show profound changes in chromatin structure that may affect the course of disease in patients. * A better understanding of these diseases and the genetic changes associated with them may be helpful in developing new treatments for them. Objectives: * To evaluate people with cancer of the lung, pleura or esophagus for participation in NCI clinical trials. * To obtain biopsies (small pieces of tissue) from tumor, normal tissue and blood samples to learn more about the cellular changes in blood and tissue in tumors of the lung, esophagus and pleura and surrounding structures in the chest. Eligibility: Patients 2 years of age and older with cancer of the lung, esophagus, pleura, mediastinum or chest wall, or cancers of other origin that have invaded the lung. Note: Patients \>= 2 years of age and under 18 years of age may only participate in research sample collection. Design: * Up to 1310 patients may be included in this study. * Patients undergo standard tests for evaluating the stage of their disease and for determining eligibility for an NCI investigational treatment study. * All patients undergo bronchoscopy and bronchoalveolar lavage ("washing" with salt water) to assess their tumor and collect a sample of normal tissue. Patients whose tumor is located on the outside portion of the lung may also undergo thoracoscopy to obtain a tumor sample. For bronchoscopy and bronchoalveolar lavage a tube with a light is passed through the nose or mouth into the lungs to examine the airways. Salt water is injected through the tube and then withdrawn to obtain cells for laboratory studies. For the thoracoscopy a small tube with a light is put through a small hole in the chest to obtain the tumor sample. Both procedures are usually done under general anesthesia. The tissue is examined to identify cell characteristics of people who respond to certain therapies and to identify markers on the surface of the tissue that may be useful in future research and treatment. * Blood and urine samples are collected from patients. * Patients who are eligible for a treatment study at NCI are offered participation in the study. * Patients for whom standard surgery, radiation or chemotherapy is more appropriate may receive treatment at NCI or with their own physician. * Patients who receive treatment at NCI return for follow-up examinations 4 weeks after discharge and then every 2 to 4 months depending on the nature of their cancer. Read Less

Background: * The Laboratory of Infectious Diseases (LID) Clinical Studies Unit (CSU) enrolls healthy volunteers into clinical studies to study infectious diseases. * Viruses can be highly infectious and contagious. They cause considerable illness in the United States each year and a good example of this is influenza (the flu). The LID CSU performs clinical studies to learn about these viral infections and assist in the development of vaccines and treatments for the infections. These clinical studies include influenza "challenge studies" as well as natural history studies and phase I trials involving vaccines for viruses carried by mosquitos such as Zika or Dengue virus. * In influenza challenge studies studies, doctors expose a person to a flu virus. Then they study the flu through the body's natural healing process. This information will help to find better ways to prevent the flu and may also improve treatments for the flu. * Natural history studies and phase I trials of new vaccines are performed so the researchers can learn how some viral infections occur and if new vaccines are safe and potentially effective in preventing the infections. In some of these studies, participants experience insect bites with special clean (non-infected) insects (such as mosquitos) to better understand the role of insects in these infections. Objectives: - To screen healthy volunteers for future CSU studies. Eligibility: - Healthy people between the ages of 18 and 65 Design: * The 3- to 5-hour screening exam includes the following: * Medical history and physical exam * Standard blood tests including pregnancy, Hepatitis B and C, and HIV tests * Standard urine drug testing * Electrocardiogram (ECG) to test heart rhythm and function * Chest x-ray * Eligible volunteers are enrolled in the study for up to 1 year, until they take part in a CSU study or are found to be ineligible to participate. * Volunteers may withdraw from the study pool at any time. Read Less

Background: Metastatic castration sensitive and castration resistant prostate cancer (mCSPC and mCRPC) are prostate cancers that have spread to other parts of the body. Use of the drug docetaxel with androgen deprivation therapy can improve survival for men with mCSPC. Researchers want to see if combining this treatment with other drugs can help delay the time it takes for mCSPC and mCRPC to get worse. Objective: To learn if giving docetaxel with M9241 is safe and effective for men with prostate cancer. Eligibility: Men age 18 and older with mCSPC or mCRPC. Design: Participants will be screened with a medical history and physical exam. Their diagnosis will be confirmed. Their symptoms and how well they do their normal activities will be reviewed. They will have blood and urine tests. Their heart will be evaluated. They will have imaging scans of the chest, abdomen, and pelvis. They will have bone scans with intravenous (IV) injections of Tc99 to check for tumor spread in the bones. Some screening tests will be repeated during the study. Participants may have tumor biopsies. Participants will get treatment in cycles. Each cycle will last 21 days. They will get docetaxel through IV infusion. They will get M9241 as an injection under the skin. Participants with mCSPC will have up to 6 cycles. Those with mCRPC will be treated until they cannot tolerate the side effects or their disease gets worse. Participants will have a follow-up visit 30 days after treatment ends. Those with mCSPC will then have follow-up visits at the clinic every 3 months.... Read Less

The purpose of the present study is to examine the pharmacokinetics and pharmacodynamics of cannabigerol (CBG; CHI-914), a naturally occurring chemical constituent of the cannabis plant formulated for oral consumption, in healthy adults. The study will utilize a within-subjects, placebo-controlled, double-blind, ascending-dose design.Upon enrollment, participants will complete 5 oral dosing conditions (placebo, 25, 50, 100, and 200 mg CBG). Each condition will consist of a single acute drug exposure, followed by an 8-hour period to evaluate acute pharmacodynamic and pharmacokinetic drug effects. This work will provide novel data on the pharmacokinetics, pharmacodynamic effects, and safety of acute oral CBG dose administration in humans. Read Less

SISTER is a Phase-II, prospective, randomized, placebo-controlled, blinded, dose finding trial that aims to determine the safety and preliminary efficacy of TS23, a monoclonal antibody against the alpha-2 antiplasmin (a2-AP), in acute ischemic stroke. Read Less

This study is researching an experimental drug called REGN5381 (called "study drug"). The study is focused on patients with heart failure with reduced ejection fraction (ie, the heart is not functioning as well as it should). The aim of the study is to see how safe, tolerable, and effective the study drug is. The study is looking at several other research questions, including: * What side effects may happen from taking the study drug * How much study drug is in the blood at different times * Whether the body makes antibodies against the study drug (which could make the study drug less effective or could lead to side effects) Read Less

A phase 3b, Randomized, Controlled Trial of Nadofaragene Firadenovec vs. Observation in Participants with Intermediate Risk Non-Muscle Invasive Bladder Cancer (IR NMIBC) Read Less

Study GZRA is a master protocol that will support 2 independent studies, GZ01 and GZ02. Participants will be assigned to the appropriate study prior to randomization. The purpose of the studies is to evaluate the efficacy and safety of orforglipron in participants who have moderate-to-severe OSA and obesity or overweight. Study GZ01 will include participants who are unable or are unwilling to use PAP therapy. Study GZ02 will include participants who are on PAP therapy for at least 3 months at time of screening and plan to continue PAP therapy during the study. Read Less

The main purpose of this study is to evaluate the effects of LY3541860 in adult participants with moderately to severely active Rheumatoid Arthritis with inadequate response to a least one biologic disease-modifying antirheumatic drug (bDMARD)or targeted synthetic disease-modifying antirheumatic drug (tsDMARD). Study participation is approximately 50 weeks, including a 6-week screening period, 24-week treatment period, and a 20-week safety follow up period. Read Less

The goal of this protocol is to identify families with inherited movement disorders and evaluate disease manifestations to establish an accurate clinical diagnosis by using newest technological advances and investigate the underlying molecular mechanisms. Studies of inherited movement disorders in large families with good genealogical records are especially valuable. Patients with diseases of known molecular basis will be genotyped in order to investigate phenotype/genotype correlation. Patients with disease of unknown or incomplete genetic characterization will be studied with a hope of contributing to the identification of specific disease-causing genes and genetic mechanisms responsible for a specific disorder.... Read Less

Human phagocytic cells such as polymorphonuclear leukocytes (PMNs) are readily mobilized to sites of infection and ingest microorganisms by a process known as phagocytosis. The combined effects of reactive oxygen species (ROS) and proteolytic peptides and enzymes released into forming bacterial phagosomes kill most ingested bacteria. However, many human bacterial pathogens have devised means to subvert normal phagocyte responses and the innate immune response and cause severe disease. The overall objective of this study is to elucidate specific features of pathogen-phagocyte interactions that underlie evasion of the innate immune response or contribute to the pathophysiology of disease or inflammatory disorders. Therefore, specific projects will: 1. Identify and characterize specific mechanisms used by pathogenic microorganisms to evade or subvert normal phagocyte responses and therefore cause disease. 2. Investigate phagocyte response mechanisms to specific pathogenic microorganisms. 3. Identify specific bacterial structures and/or (gene) products that dictate differences in phagocyte responses among a range of pathogens so that generalized statements can be made about the pathophysiology of disease states. The studies will be performed using multiple techniques including state-of-the-art equipment for genomics and proteomics strategies to identify target bacterial genes/proteins of interest or those up-regulated in phagocytes. Phagocyte-pathogen interactions will be examined using fluorescence-based real-time assays and video microscopy, confocal and electron microscopy in combination with enzymatic assays for ROS production, routine biochemistry, immunology and cell biology. Implementing these studies will require isolation of phagocytic leukocytes from venous blood of healthy human volunteers. The study population will be all-inclusive except in certain instances where individuals possess genetic defects that impair phagocyte function (e.g., myeloperoxidase-deficiency) or have altered phagocyte function due to outside influences such as recent bacterial or viral infection. The proposed studies will likely provide new information pertinent to understanding host cell-pathogen interactions and the pathophysiology of inflammatory conditions. Read Less