All Clinical Trials

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. Read Less

Background: Genitourinary cancers are some of the most common types of cancer. They are lethal when they spread. The drug M7824 blocks the paths that cancer cells use to stop the immune system from fighting cancer. The drug PDS01ADC triggers the immune system to fight cancer. Researchers want to learn if these drugs can help fight these cancers when given with and without Stereotactic Body Radiation Therapy (SBRT) radiation. Objective: To learn if M7824 and PDS01ADC, with or without SBRT, can help the immune system to fight cancer better. Eligibility: People 18 and older with cancer that started in the bladder, kidneys, or other genitourinary organs (but not the prostate) and has spread to other parts of the body. Design: Participants will be screened with: medical history physical exam ability to do their normal activities blood tests urine tests electrocardiogram body scans. Participants will give a tumor sample or have a tumor biopsy. Screening tests will be repeated during the study. Participants will get PDS01ADC . It is injected under the skin every 4 weeks. They will also get M7824 through an intravenous (IV) infusion every 2 weeks. For this, a small plastic tube is put into a vein in the arm. They will get these drugs in 28-day cycles until they leave the study. They may have SBRT. Participants will give tissue and saliva samples. Participants will have a follow-up visit 30 days after treatment ends. Then they will get phone calls or emails every 12 weeks indefinitely. ... Read Less

The aim of this study is to understand how well a 6-week virtual yogic breathing exercise program (YBEP) will improve breathing, speech, and emotional well-being in people with amyotrophic lateral sclerosis (ALS). Read Less

Background: * Cancer has an enormous impact on the psychological and social well-being of the family unit. The life-threatening connotations of cancer single out the ill child from his peer/family group as one who is different, and often unable to maintain a normal lifestyle. Physical sequelae of cancer and its treatment accentuate the differences between these children and their normal peers/siblings. * It is important that children with cancer be prepared to function outside of protected situations and begin to develop skills of separation and independence. For healthy children, some of these latter skills are acquired by a camping experience. Such an experience for the patient with cancer is frequently precluded by their dependence on medical facilities and the physical limitations of their activities. * The goal of this study will be to assess the short and long term benefits of the "normalized" camping experience, provided in conjunction with Special Love, Inc., on the patients and staff. In particular, we will seek to determine whether such a comprehensive experience is capable of influencing the attitudes and life experiences of patients and staff in a positive manner. Objectives: -To evaluate the impact of an enriched normalized camping experience on the quality of life of the pediatric cancer patient. In particular, attempts will be made to measure the manner in which this experience influences the child's sense of well-being and self-esteem as well as his or her relationship with parents, family, and peers. Eligibility: * Children 7-17 years of age who are currently being treated for cancer or are up to 3 years post therapy OR Young adults with cancer (YACers) 18-25 years of age who are acting as counselors at Camp Fantastic * All children/young adults will be selected for camp after careful screening by a multidisciplinary committee consisting of medical and program directors. * At the discretion of the multidisciplinary committee consisting of medical and program directors, special exceptions may be made for children with extenuating circumstances. Design: * Assessment of benefit may include interviews with children and families before, during and following camp. Observational data on the child's performance at camp will be noted. * Medical and nursing personnel will consist of staff from the Pediatric Branch at the NCI, other units within the NIH, and participating institutions. * Special Love members, the Program Director at the 4-H Center camp (site of the camp) and Pediatric Branch staff at the NCI will coordinate the camp program, taking into account the medical needs of each camper. * Every attempt will be made to provide a full agenda of age appropriate activities for the patients. * The length of the camping experience for children with cancer will be for 7 days beginning on a Sunday and extending through the following Saturday morning. Patients will be transported to the camp from the NIH Clinical Center and the Virginia hospitals by bus. Read Less

This study will collect blood plasma and white blood cells from individuals using a procedure called apheresis. Apheresis is a method of collecting larger quantities of certain blood components that can safely be collected through a simple blood draw. The blood components will be used in laboratory research studies. Patients 18 years of age and older who are currently enrolled in a NIH clinical research protocol may participate in this study. Relatives of patients and normal healthy volunteers will also be enrolled. Individuals will undergo one of the following two apheresis procedures: * Automated pheresis Blood is drawn through a needle placed in an arm vein and circulated through a cell separator machine. The plasma (liquid part of the blood) and white cells are extracted, and the red cells are re-infused into the donor through the same needle or a needle in the other arm. An anticoagulant (medication to prevent blood from clotting) is usually added to the blood while in the machine to prevent it from clotting during processing. * Manual pheresis One unit (1 pint) of blood is drawn through a needle placed in an arm vein, similar to donating a pint of whole blood. The red blood cells, with or without plasma, are separated from the rest of the blood and returned to the donor through the same needle. Manual pheresis will be done only when a person s estimated total blood volume or red cell count is too low to safely permit removal of blood through a pheresis machine. An adult small in size or markedly anemic, for example, may fall into this category. Some of the blood collected through apheresis may be stored for future studies of HIV disease and immune function and for HLA testing, a genetic test of markers of the immune system. Some of the blood may be used to screen for different types of viral liver infections, such as hepatitis A, B, C, D, E, F, or G. ... Read Less

Background: -Sjogren s Disease (formerly: Sjogrens Syndrome, Sj(SqrRoot)(Delta)gren s syndrome) is a disease that affects about 1-4 million Americans. It is more common in women. It mainly affects the glands that produce saliva and tears, leading to dry eyes and dry mouth. The cause of Sjogren s Disease is unknown, but inflammation plays an important role. The purpose of this study is to learn more about Sjogren s Disease. Objectives: -To better understand how Sjogren s Disease begins and how it affects patients so that we can develop better ways to treat them. Eligibility: * Participants must be 16 years of age or older. * They must have a diagnosis of Sjogren s Disease or have at least two symptoms of Sjogren s Disease. Design: * People taking part in the study will come to the NIH Clinical Center for at least three visits. * During these visits, participants will have a medical history and physical exam. They will have oral and dental assessments, and saliva collection. Lab tests (blood and urine) and dry eye exams will be done. Participants will answer questionnaires and have salivary scintigraphy (adults only unless required for diagnosis). * Other optional tests may also be done. Participants may have to come in for additional visits if they have these optional tests or if their disease changes. * The only treatment provided as part of this study is for medical emergencies or complications that occur while you are at NIH for evaluation.... Read Less

Background: - About 15 million Americans have a food allergy. Because there are no cures or effective prevention or treatment for food allergies, researchers want to learn more about them. Objective: - To learn more about the causes and effects of food allergy and related conditions. Eligibility: * People ages 2 99 who have food allergy and/or a related genetic or other condition * Their relatives * Healthy relatives and volunteers Design: * Participants will have at least 3 visits over 1 2 years, and then once a year for up to 12 years. Each may last a day or longer. * Participants will be screened with medical history, physical exam, and questionnaires. * Participants may have the following: * Blood tests * Allergy skin prick tests: Drops of allergens are placed on the back or arm. The skin is scratched under each drop. * Leukapheresis: blood is taken from a needle in one arm, passed through a machine, and returned through a needle in the other arm. * X-rays * Esophageal string test: One end of a string is taped to the cheek and the other end is packed into a capsule. When the capsule is swallowed, the string unwinds; it is left in for at least 1 hour. * EGD and colonoscopy: Biopsies are taken from the gastrointestinal system. * Tiny biopsies of skin * Photographs of the body * Collection of cells through: * Swab of nose, inside of cheek, or skin * Gentle skin scrape * Tape stripping: piece of tape is put on the skin and pulled off. Read Less

Background: Proteus syndrome is a rare overgrowth disorder. Most people begin to have symptoms between 6 months and 2 years of age. There are very few living adults with this disease. There is also no known treatment for it. Researchers want to see if a new drug can slow down or stop overgrowth in people with Proteus syndrome. Objective: To learn if miransertib is a safe and effective treatment for Proteus syndrome. Eligibility: People ages 3 and older with Proteus syndrome. Design: Participants will be screened with a medical checkup. They will answer questions about their medical history and current health. They will have a physical exam with vital signs. They will have an electrocardiogram to measure their heartbeat. They will give blood and urine samples. They will repeat the screening tests during the study. Participants will take a miransertib pill once a day. They will bring their empty pill bottles with them to the NIH when they visit. If they can t swallow a pill, researchers will try to find other ways for them to take the drug. Participants will have X-rays, ultrasounds, and imaging scans. Photos may be taken of their feet and other parts of the body that have or develop signs of Proteus syndrome. Participants will have lung function tests to measure how much and how fast air moves out of their lungs. Participants will complete surveys about their levels of pain, physical functioning, and quality of life. Participants may have additional tests performed to assess their individual disease. They may have consultations with other specialists. Participation lasts about 4 years. Participants will have 20-30 visits at the NIH. Read Less

This phase II trial evaluates response-guided low-dose tamoxifen for reducing breast density in women who are at higher than average risk for breast cancer. Increasing breast density is a well established risk factor for breast cancer. Tamoxifen is a selective estrogen receptor modulator. It works by blocking the effects of the hormone estrogen in the breast. Tamoxifen has been shown to reduce breast density, even at reduced dosages, and is approved for the prevention of breast cancer. Read Less

This study will evaluate and treat patients with filarial infections to explore in depth the immunology of the disease, including susceptibility to infection, disease development, and response to treatment. Filarial infections are caused by parasitic worms. The immature worm (larva) is transmitted to a person through a mosquito bite and grows in the human body to 2 to 4 inches in length. Although many of these infections do not produce symptoms, especially in the early stages of infection, others can have serious consequences, including swelling of the limbs or genitalia, allergic-lung problems, skin rash, eye inflammation that can lead to blindness, and heart disease. This protocol does not involve any experimental diagnostic procedures or treatments, and will use only procedures employed in the standard practice of medicine. Persons between 3 and 100 years of age diagnosed with or suspected of infection with Wuchereria bancrofti, Bugia malayi, Onchocerca volvulus, Loa loa, or other parasitic worms may be eligible for this study. Participants will have routine tests to determine the specific type of filarial infection. These may include special tests of the lungs, skin or heart, depending on the type of parasite suspected. Patients with skin reactions may have a "punch biopsy" to examine a small piece of affected skin. For this procedure, an area of skin is numbed with an anesthetic and a small circular area, about 1/3-inch in diameter and 1/2-inch thick, is removed using a sharp cookie cutter-type instrument. Some patients may require bronchoalveolar lavage. For this procedure, the mouth and throat are numbed with lidocaine jelly and spray and, if needed, a sedative is given for comfort. A small plastic tube is placed in a vein to give medications. A pencil-thin tube is then passed through the nose or mouth into the lung airways to examine the airways. Salt water is injected through the bronchoscope into the air passage, acting as a rinse. A sample of the fluid is then withdrawn and examined for infection, inflammatory cells and inflammatory chemicals. (Bronchoalveolar lavage is done only if medically necessary and only on patients 21 years or older.) Once the diagnosis is established, standard treatment will be instituted with either diethylcarbamazine or ivermectin, depending on the type of infection. Additional procedures for research purposes include: * Extra blood draws to study immune cells and other immune substances. (This is the only research procedure that will be done in - More frequent and extensive follow-up evaluations than usual for routine care. They will include physical examination and blood studies. * Urine collections at specified periods, possibly including 24-hour collections. * Skin tests to examine the body s reaction to allergens-common environmental substances, such as cat dander or pollen-that cause an allergic reaction. The test is done in one of two ways: either the skin is lightly scratched and an allergen extract is placed over the just-broken skin, or a very fine needle is used to inject a small amount of allergen under the skin. In both methods, the site is monitored for swelling or hives in the next 48 hours. * Leukapheresis (only on patients 21 or older ) to collect quantities of white blood cells. Whole blood is collected through a needle in an arm vein, similar to donating blood. The blood circulates through a machine that separates it into its components, and the white cells are removed. The rest of the blood is returned to the body, either through the same needle or through another needle in the other arm. 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

Background: - Researchers at the National Institutes of Health give many tests of hearing and balance. These tests can help detect problems that affect hearing or balance. It is important to know exactly how healthy people perform on each of these tests. This information will indicate when a test result is normal and when a test result shows a problem. Researchers also want to determine the best methods for each test. Objectives: - To test different types of hearing and balance tests, and collect information on normal values for each test. Eligibility: - Healthy volunteers between 5 and 80 years of age. Design: * This study will require a single visit to the National Institutes of Health Clinical Center. It will include both screening tests and study tests of hearing and balance. Sometimes, a second visit may be required if a test is designed to measure the same thing on 2 different days. Each visit will last between 2 and 5 hours, depending on the number of tests scheduled per visit. * Participants will have a physical exam and medical history. They will also have basic tests to check for normal hearing and balance. * Participants may have different hearing tests, including the following: * Auditory Evoked Potentials to study how the ears and brain handle sound information. * Auditory Processing Tests to study how a person processes complex sounds like speech in background noise. * Tests of middle ear and inner ear function. * Participants may have different balance and inner ear tests, including the following: * Balance test on a tilting platform. * Different tests to measure how well the eyes, ears, and brain work together to help maintain balance. * Treatment will not be needed as part of this study. Read Less