Background: There are 461 conditions that affect the bones (skeletal disorders). Many of these are not well understood and do not have any specific treatments. Researchers want to collect more data about these conditions. Objective: To gain more information about the causes of skeletal disorders and how they progress over time. Eligibility: People ages 2 months or older with known or suspected skeletal disorders or history of pregnancy affected by skeletal findings. Also, healthy family members of affected enrolled participants. Design: Participants can take part in the study either remotely or in person. Those who take part remotely may send in medical records, blood samples, photographs, and other materials. Participants medical records will be reviewed. They may give blood and/or urine samples. They will give blood, saliva, or tissue samples for genetic tests. They may have genetic counseling. Participants ages 2 years and older may have different kinds of imaging scans, such as x-rays. For these scans, they may have to lie still while machines take pictures of their bones. Participants with skeletal disorders who come to the clinic will be examined. They may be asked to stay in the hospital for a few days to take extra tests. They may have a bone or skin biopsy. Participants with skeletal disorders may be photographed to show the effects of their disorder and how it changes over time. For participants with skeletal disorders, their blood or tissue samples may be used to make a special type of stem cell. These cells can be used in the laboratory to make many other types of cells. A large supply of these cells may be created for research. Participation will last indefinitely.

Type: Observational

Start Date: Jan 2022

open study

Background: The pituitary gland produces hormones. A tumor in this gland can cause it to produce too much of the hormone cortisol. Too much cortisol in the body causes Cushing disease. This disease causes many problems. Some of these problems might persist after the disease is cured. Objective: To find out the long-term effects of exposure to high levels of cortisol during childhood and adolescence. Eligibility: People ages 10-42years who were diagnosed with Cushing disease before age 21 and are now cured and have normal or low cortisol levels People related to someone with Cushing disease Design: Participants will be screened with a medical history. Participants will complete an online survey. This will include questions about their or their child s physical and mental health. All participants will be seen at 5 -year intervals after cure of Cushing disease (5yr, 10yr, 15yr, 20yr (last visit)) Participants who have a relative with Cushing disease will have a medical history and blood tests or cheek swabs. Participants who have the disease will have: Physical exam Blood tests Cheek swab DXA scan: A machine will x-ray the participant s body to measure bone mineral content. For participants who are still growing, a hand x-ray Participants with the disease may also have: Hormone stimulation test: Participants will get a hormone or another substance that will be measured. Serial hormone sampling: Participants blood will be measured several times through a thin plastic tube in an arm vein. Urine tests: Participants urine may be collected over 24 hours. MRI: Participants may have a dye injected into a vein. They will lie on a table that slides into a machine. The machine will take pictures of the body.

Type: Observational

Start Date: Mar 2019

open study

Background: - Viral infections are an important cause of illness and death in hospitalized patients as well as outpatients. New strains of viruses may appear and infect both healthy people and those with weak immune systems. A better understanding of these new virus strains (such as SARS-CoV-2, the virus that causes COVID-19) may help to control and prevent these infections. In particular, some viral infections that are less problematic in healthy persons can be life threatening in persons with weak immune systems, and viruses may be able to evolve more rapidly in persons with weak immune systems and therefore develop resistance to existing treatments. Researchers are interested in collecting samples and information from otherwise healthy persons or persons with weak immune systems to study the effects of viruses and their development. Objectives: - To collect samples and data from individuals who have been exposed to or have contracted viral infections. Eligibility: - Individuals of all ages who have been diagnosed with a viral infection are suspected to have a viral infection, or have been in close contact with someone with a suspected or actual viral infection that is of interest to investigators in the Laboratory of Infectious Diseases. - Healthy persons and persons with weak immune systems (immunocompromised individuals) are eligible to participate. Design: - Participants will be pre-screened to determine if they meet the eligibility criteria for the trial. - If eligible, evaluation may include a medical chart review, a history and physical examination, review of clinical reports from outside hospitals and laboratories, and review of tissue biopsies. - Study procedures may include collection of blood, urine, saliva, nasal fluid sampling, throat swabs, stool, and genital swabs. For participants who have specimens collected as part of their medical care (e.g. wound swabs, spinal tap, bronchoscopy, liver biopsy etc.), researchers may use leftover specimens from the clinical laboratory for testing. - Specimens may be collected up to 4 times per week during the first 2 weeks after enrollment, and then as many as 2 times per week for up to 2 years. Some participants may be asked to continue providing specimens if there is concern for relapse or recurrence of the infection. - Treatment is not offered under this study.

Type: Observational

Start Date: Mar 2011

open study

Background: Allergic or sinus diseases can affect the skin, sinuses, airways, and other parts of the body. Examples include pollen and environmental allergies, food allergies, asthma, and eczema. To learn more about how to prevent and treat these diseases, researchers need to study data, blood, fluid, and tissue samples from people affected by them. Objective: To collect data, blood, fluid, and tissue samples from people with allergic or sinus diseases. Eligibility: People aged 3 to 100 years with allergic or sinus diseases. Design: Participants will have at least one clinic visit, and most participants will have a baseline visit, annual visit, and an end of study visit. The duration of the study is 1 to 3 years. During the first clinic visit, the following procedures will be done to collect data, blood, fluid, and tissue samples: - Blood will be collected. - Cells and fluid may be collected from the inside of the nose using a long swab, and a small piece of skin may be scraped from inside the nose. - Skin cells will be collected by rubbing with a cotton swab. - A urine sample will be collected. - Allergy skin prick tests. Allergy-causing substances will be placed on the back or arm and the skin underneath gently scratched. If the participant is allergic to the substance, the skin may become red, itchy, and swollen locally ( at the site of the test). - Lung function test. Participants will breathe into a machine that measures the air moving in and out of their lungs. - If, as part of their routine care, participants are undergoing procedures such as having nasal polyps removed, skin tissue samples taken, or gastrointestinal biopsies, additional tissues may be collected for this study. - Participants will complete online questionnaires regarding their symptoms, health, and life. Participants may return for more visits for up to 3 years.

Type: Observational

Start Date: Jan 2025

open study

Background: Inflammatory conditions can cause symptoms like fevers, arthritis, and rash. Systemic juvenile idiopathic arthritis (sJIA) is one of these conditions. So is adult-onset Still s disease (AOSD). Their causes are unknown. Researchers want to learn more about these conditions. This includes genetic changes and environmental factors. Objective: To study sJIA and AOSD in children and adults over time. Eligibility: People with known or suspected sJIA, AOSD, or similar inflammatory condition Design: Participants will be screened with a phone call. Participants will have 1 visit. It may be outpatient or they may be admitted to the clinic. The visit may last up to 5 days. Participants will have: - Medical history - Physical exam - Musculoskeletal exam - Questions about overall health and quality of life, disease activity, functional status, and cognitive ability. Participants may also have: - Pictures taken of their skin, joints, or spine - Blood, urine, and stool tests - Scans or X-rays of joints with arthritis - Chest X-ray - Heart tests - Skin biopsy. The skin will be numbed. The top layers of a small area will be scraped off. Participants who have a joint aspiration may provide a fluid sample. The joint will be prepared, then fluid is removed by needle. A corticosteroid may be injected. Participants who have a bone marrow biopsy may provide sample cells. Participants may be seen by NIH specialists. Members of the participant s family and healthy volunteers may give blood or saliva samples for genetic testing. Participants may repeat some study tests every 6 months.

Type: Observational

Start Date: May 2018

open study

Background: The drug Nivolumab has been approved to treat some cancers. Researchers want to see if it can slow the growth of other cancers. They want to study its effects on cancers that may have not responded to chemotherapy or other treatments. Objectives: To see if Nivolumab slows the growth of some types of cancer or stops them from getting worse. To test the safety of the drug. Eligibility: People 12 and older who have Epstein-Barr Virus (EBV)-positive lymphoproliferative disorders or EBV-positive non-Hodgkin lymphomas with no standard therapy Design: Participants will be screened with: Medical history Physical exam Blood and urine tests CAT scan of the chest, abdomen, and pelvis Tumor and bone marrow biopsies (sample taken) Magnetic resonance imaging scan of the brain Lumbar puncture (also known as spinal tap) Positron emission tomography/computed tomography scan with a radioactive tracer Every 2 weeks, participants will get Nivolumab by vein over about 1 hour. They will also have: Physical exam Blood and pregnancy tests Review of side effects and medications During the study, participants will repeat most of the screening tests. They may also have other biopsies. After stopping treatment, participants will have a visit every 3 months for 1 year. Then they will have a visit every 6 months for years 2-5, and then once a year. They will have a physical exam and blood tests. ...

Type: Interventional

Start Date: Apr 2018

open study

The proposed study aims to evaluate, investigate, and follow-up patients suffering from acute and chronic liver disease. The study will focus on understanding diseases affecting the liver. Patients participating in the study will first undergo a routine check-up as an outpatient. They will be asked to provide blood and urine samples for laboratory testing and will undergo an ultrasound of the liver. Ultrasound examinations use sound waves to determine the size and texture of the liver. After the initial visit subjects will be requested to follow-up once a year at the outpatient department for a similar check-up. Additional tests may be requested throughout the study to provide information for other research studies and individual consent will be requested. These tests may include liver biopsies, skin biopsies, and / or specialized blood, plasma, and lymphocyte examinations. Subjects that qualify for medications presently being studied may be offered the opportunity to benefit from experimental therapy.

Type: Observational

Start Date: May 1992

open study

Background: - GATA2 deficiency is a disease caused by mutations in the GATA2 gene. It can cause different types of leukemia and other diseases. Researchers want to see if a stem cell transplant can be used to treat this condition. A stem cell transplant will give stem cells from a matching donor (related or unrelated) to a recipient. It will allow the donor stem cells to produce healthy bone marrow and blood cells that will attack the recipient s cancer cells. Objectives: - To see if stem cell transplants are successful at treating GATA2 mutations and related conditions. Eligibility: - Recipients who are between 6 and 70 years of age and have GATA2 deficiency. Design: - All participants will be screened with a physical exam and medical history. Blood samples will be collected. Recipients will have imaging studies and other tests. - Recipients will have chemotherapy or radiation to prepare for the transplant. On the day of the transplant, they will receive the donated stem cells. - Recipients will stay in the hospital until their condition is stable after transplant. - Frequent blood tests and scans will be required for the first 6 months after the transplant, followed by less frequent visits over time.

Type: Interventional

Start Date: Jul 2013

open study

Background: - Uveal coloboma is a condition where the eye does not form normally. It occurs early in the fetus s development during pregnancy. It can lead to different kinds of eye problems, including blindness. Uveal coloboma is part of a spectrum of developmental eye conditions that include anophthalmia and microphthalmia, typically referred to as "MAC". Several genes have been linked to MAC, but the cause of most causes are hard to find. Researchers want to study the genes of people who have MAC and genes from their close, unaffected relatives (such as parents and siblings). Objectives: - To study the genes associated with MAC. Eligibility: - Individuals at least 1 years of age who either have MAC or are an unaffected relative (such as a parent or sibling). Design: - Participants will have a physical exam and medical history. They will also have a full eye exam. - Participants with MAC may have other exams, such as imaging studies and hearing assessments. - All participants will also provide blood, cheek swab or saliva or DNA samples for genetic testing.

Type: Observational

Start Date: Jan 2013

open study

Background: - Painful stimuli cause changes in a network of brain regions called the "Pain Matrix." But most of these regions respond to many other stimuli, not just pain. Researchers want to understand how different factors influence pain. They want to test what happens when people expect different levels of pain and receive treatments that can modify pain. They want to see if these factors influence decisions about pain and how the body responds to it. They also want to compare pain with responses like taste and vision. Objectives: - To better understand how pain and emotions are processed and influenced by psychological factors. Eligibility: - Healthy volunteers ages 18-50. Design: - This study requires 1 to 2 clinic visits that last 1 to 3 hours. - Participants will be screened with medical history and physical exam. - Some participants will have one or more magnetic resonance imaging (MRI) scans of their brain. For MRI, participants will lie on a table that slides in and out of a cylinder. The scanner makes loud knocking noises. They will get earplugs. - Participants' heart activity will be recorded with electrocardiogram. Their pulse, sweating, and breathing will be monitored. - Some participants will take a taste test. Others may perform simple tasks. Others may receive pain in their arm, leg, or hand. The pain will come from heat or electric shocks. Others may judge pain using a topical pain-relieving cream. Some of these tests may be given during MRI. - Participants will fill out questionnaires. - The study will last 3 years.

Type: Interventional

Start Date: Jun 2015

open study

Background: - Electrical impedance myography (EIM) is a new technique being studied to see if it is helpful in evaluating muscle disorders and nerve disorders. EIM looks at how a mild, painless electrical current travels through muscles. Researchers want to gain experience in using the EIM device. They will collect information on the results of using it on people with and without nerve and muscle diseases, and compare that with information from other standard tests. First, they will test the device on healthy people. Then they will test people with a variety of neuromuscular diseases. Because the test is noninvasive and not painful, researchers will test both children and adults. Objectives: - To gain experience using the EIM muscle testing device. Eligibility: - Healthy volunteers at least 2 years old. - Individuals at least 2 years old who have neuromuscular disease. Design: - Participants will be screened with a medical history and physical exam. - Participants will have one 2-3 hour clinic visit. Researchers may request follow-up visits. - Participants will be tested with the EIM device. The device and small electrodes will be placed on their skin. An electric current will pass through the device, but the participants will not feel this. - Participants may have an ultrasound test. A gel will be put on their skin, and a device will be moved over the skin. - Participants may have a nerve test. Electrodes will be placed on their skin, and they will feel a small shock. - Participants may have a test where a thin needle is inserted in their muscle.

Type: Interventional

Start Date: Jun 2013

open study

Background: Stem cell transplants (called hematopoietic stem cell transplantation, or HSCT) are used to treat various diseases. But when the cells for this procedure are donated by someone other than the person who receives the HSCT ( allogeneic HSCT ), the recipient has an increased risk of lung inflammation and scarring. This happens when their immune cells attack healthy lung cells. In this natural history study, researchers will look for the best ways to detect developing lung inflammations earlier after an HSCT. Objective: To see if certain tests can detect early signs of lung inflammation in people after HSCT. Eligibility: People aged 5 to 70 years who will have HSCT as part of another NIH study. Design: Participants will undergo these tests prior to their HSCT. These tests will then be repeated regularly for 2 years: Ultra-low dose computed tomography (CT) scans. Participants will lie on a table that slides through a machine; the machine uses X-rays to get pictures of the inside of the body. This type of scan uses less radiation than normal CT scans. Bronchoscopy with lavage: Participants will be sedated. A flexible tube will be inserted through the mouth and into the airways. Salt water will be squirted into the lung, then sucked out to collect cells and fluids from the lung. Another tube with a camera may be inserted into the airways to take pictures. Blood tests. Blood will be drawn every 2 to 4 weeks. Pulmonary function tests. Participants will breathe into a machine to test their lung function. They will see how far they can walk in 6 minutes.

Type: Observational

Start Date: Apr 2024

open study

Background: - National Institute on Aging researchers are looking at studies that require large numbers of white blood cells for lab use. Standard blood samples do not provide enough white blood cells for these studies. Researchers want to use cytapheresis to collect white blood cells from volunteer donors. This procedure can collect larger amounts of white blood cells and reduce the amount of fluid and other cells that are lost. Objectives: - To use cytapheresis to collect white blood cells for study. Eligibility: - Healthy blood donors at least 18 years of age. Design: - Participants will be screened according to the usual blood donation procedures. - Participants will provide white blood cells through cytapheresis. The blood cells will be collected in a machine that separates the white blood cells from the rest of the blood. The rest of the blood will be returned to the donor. - Participants may have this type of donation every 56 days (six times per year). They will be asked to become a repeat donor. A donation schedule may be set up. - Once a year, participants will have blood tests to continue to be eligible as a donor.

Type: Observational

Start Date: Jan 2003

open study

Jansen s Metaphyseal Chondrodysplasia (JMC) is a very rare disorder with only approximately 30 people known to have the disease worldwide. It is caused by parathyroid hormone 1 receptor (PTH1R) variants leading to constitutive activation of the receptor for parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP). PTH1R is predominantly expressed in the kidneys and bone and growth-plate chondrocytes. Individuals with JMC develop severe growth impairment resulting in significant short stature, scoliosis, frequent fractures, bone pain, mineral-ion abnormalities (typically hypercalcemia and hypercalciuria), hypertension, and chronic kidney disease due to nephrocalcinosis and nephrolithiasis. Children often undergo multiple surgeries for skeletal fractures and deformities; mobility is commonly impaired, usually requiring assistive devices for ambulation. Other complications may include premature closure of cranial sutures and cranial nerve compressions with the potential for vision and/or hearing loss [1-3]. Physical function impairment and the need for complication-related operations have profound deleterious effects on quality of life in individuals with JMC. There are currently no approved therapies for JMC, and novel therapies are critically needed to prevent irreversible disease complications and improve patient quality of life. The inventors of the drug, parathyroid hormone inverse agonist (PTH-IA), have considerable expertise in both the basic and clinical aspects of PTH/PTHrP receptor molecular biology and pharmacology. They reported the first PTH1R JMC mutations (including the H223R mutation) over 20 years ago and identified certain PTH antagonist ligands that function as inverse agonists on the PTH1R JMC mutant receptors [2, 4]. These ligands suppress the mutant receptor s elevated basal rates of cAMP signalling, as assessed in cultured cells and animal models. In vivo studies confirm that inverse agonist ligands may be effective in treating JMC. This study involves the use of PTH-IA, a 30-amino acid PTH inverse agonist ligand with the amino acid sequence [Leu11,dTrp12,Trp23,Tyr36]-PTHrP(7-36)NH2. We hypothesize that PTH-IA will be a safe and effective treatment for individuals with JMC.

Type: Interventional

Start Date: May 2026

open study

Background: When people have a stroke, they often have difficulty moving their arms and hands. Transcranial magnetic stimulation (TMS) can improve how well people with and without stroke can move their arms and hands. But the effects of TMS are minor, and it doesn t work for everyone. Researchers want to study how to time brain stimulation so that the effects are more consistent. Objective: To understand how the brain responds to transcranial magnetic stimulation so that treatments for people with stroke can be improved. Eligibility: Adults ages 18 and older who had a stroke at least 6 months ago Healthy volunteers ages 50 and older Design: Participants will have up to 5 visits. At visit 1, participants will be screened with medical history and physical exam. Participants with stroke will also have TMS and surface electromyography (sEMG). For TMS, a brief electrical current will pass through a wire coil on the scalp. Participants may hear a click and feel a pull. Muscles may twitch. Participants may be asked to do simple movements during TMS. For sEMG, small electrodes will be attached to the skin and muscle activity will be recorded. At visit 2, participants will have magnetic resonance imaging (MRI). They will lie on a table that slides into a metal cylinder in a strong magnetic field. They will get earplugs for the loud noise. At visit 3, participants will have TMS, sEMG, and electroencephalography (EEG). For EEG, small electrodes on the scalp will record brainwaves. Participants will sit still, watch a movie, or do TMS. Participants may be asked to have 2 extra visits to redo procedures.

Type: Observational

Start Date: Sep 2018

open study

The purpose of this study is to use brain imaging technology to measure changes in blood flow to areas in the brain as individuals perform intellectual tasks. This study will use functional magnetic resonance imaging (fMRI) to examine blood flow to areas of the brain as participants engage in tasks associated with visual perception, visual recognition, and memory.

Type: Observational

Start Date: Sep 1993

open study

Background: Fungal infections can cause serious disease in the lungs and other parts of the body. About 3.8 million people die with fungal infections each year. Currently, there is no way to find fungal infections in the body using imaging scans. Researchers want to see if a new tracer (a radioactive drug that collects in certain body tissues) can help find fungal infections using positron emission tomography (PET)/computed tomography (CT) scans. Objective: To test a new tracer ([18F]Fluorocellobiose) for PET/CT scans in people with and without fungal infections. Eligibility: People aged 18 years and older who have fungal infections. Healthy volunteers are also needed. Design: Participants will have 3 clinic visits. The first visit will be for screening. Participants will have a physical exam with blood tests and a test of their heart function. The second visit will be for PET/CT scanning. A thin tube called a catheter will be inserted into a vein in the arm. The study tracer will be given through the catheter. For the scans, participants will lie on a padded bed that slides through a donut-shaped machine. The machine will take pictures of the inside of the body from the head to the upper thighs. Some participants will have only 1 scan; others will have 2 scans. The second scan will be about 90 minutes after the first one. The third visit will be for repeat blood and urine tests.

Type: Interventional

Start Date: Jul 2026

open study

Background: Allogeneic hematopoietic stem cell transplant involves taking blood stem cells from a donor and giving them to a recipient. The transplants are used to treat certain diseases and cancers. Researchers want to see if the transplant can treat VEXAS Syndrome. Objective: To see if stem cell transplants can be successfully performed in people with VEXAS and even improve the disease. Eligibility: People ages 18-75 who have VEXAS Syndrome that has caused significant health problems and standard treatment either has not worked or is not available. Design: Participants will be screened with: Physical exam Medical review Blood and urine tests Heart and lung function tests Bone marrow biopsy Participants will have a chest x-ray. They will have an imaging scan of the head, chest, abdomen, pelvis, and sinus. They will have a bone density scan. They will have a dental exam and eye exam. They will meet with specialists. They will repeat some screening tests. Participants will be admitted to the NIH hospital. They have a central venous catheter put into a vein in the chest or neck. They will receive drugs to prepare their bone marrow for the transplant. They may have total body irradiation. They will receive the donor stem cells through the catheter. They will get other drugs to prevent complications and infections. After discharge, they must stay in the DC area for 3 months for weekly study visits. Participants will have study visits 30, 60, 100, 180, 210, 240, 300, and 360 days later. After that, they will have yearly visits for 2 years and then be contacted yearly by phone....

Type: Interventional

Start Date: Feb 2023

open study

Background: - Two ways to study the brain while people are moving are near-infrared spectroscopy (NIRS) and electroencephalography (EEG). NIRS uses light to look at blood flow in the brain when it is active. EEG records electrical activity in the brain. Both have been used safely for many years, even in very young children. NIRS or EEG can be used while a person is moving to show which parts of the brain are the most active. Researchers want to use NIRS and EEG to study brain activity during movement in people with cerebral palsy and healthy volunteers. Learning more about how people with and without cerebral palsy use their brain to control their muscles may lead to new ways of training people with cerebral palsy to move better. Objectives: - To study how the brain controls body movement in people with and without cerebral palsy. Eligibility: - Individuals at least 5 years of age who have cerebral palsy. - Healthy volunteers at least 5 years of age. Design: - This study has three parts. People with cerebral palsy will be selected for all three. Healthy volunteers will be asked to do only two of them. Everyone who participates will have NIRS and/or EEG exams during movement. People with cerebral palsy may also have biofeedback sessions to train coordination of movement and brain activity. - Participants will be screened with a physical exam and medical history. Urine samples may be collected. - All participants will have at least one session of NIRS and/or EEG imaging studies. Sessions may also include the following tests: - Magnetic resonance imaging to look at the brain - Electromyography to measure electrical activity of the muscles - Motion analysis of specific body parts - Ultrasound to measure activity of the muscles - Motorized, robotic, and electrical stimulation of the muscles - Other clinical tests of muscle movement as needed. - Participants with cerebral palsy will have biofeedback sessions. These sessions will help them learn to coordinate muscle movement and brain activity.

Type: Observational

Start Date: Aug 2013

open study

Background: Premature ovarian insufficiency (POI) is a condition in which women under the age of 40 years have absent or irregular menstrual cycles. POI can cause infertility, signs of menopause, osteoporosis, and other symptoms. Hormone replacement therapy (HRT) is a treatment that gives women extra hormones, such as estrogen and progesterone. HRT works well in adult women. Researchers want to find the most effective doses and regimens for adolescents. Objective: To monitor the effects of HRT on adolescents with POI. Eligibility: Female adolescents aged 11 to 19 years diagnosed with POI. Healthy volunteers are also needed. Design: All participants will have clinic visits every 6 months for 2 years. Each visit may last 2 days. Each visit may include: Blood and urine tests. A test of their heart function. A test to measure the stiffness of their blood vessels. Participants will lie flat with a blood pressure cuff on a leg and a meter on the neck while the cuff inflates. A test of their grip strength. Participants will squeeze a handheld device as hard as they can. Two scans to measure bone density. For one, participants will lie on a table while a scanner passes along their body. For the other, participants will sit in a chair and insert their forearm, then their lower leg, into a scanner. A test to measure skin pigmentation. Participants' skin will be touched lightly with a device. An optional visual exam of the vagina. Some vaginal fluid may also be collected with a cotton swab/cytobrush. Participants with POI will receive HRT. They will be given estrogen patches and progesterone pills.

Type: Interventional

Start Date: Jul 2025

open study

Background: A neuroendocrine tumor is a rare type of tumor. It comes from body cells called neuroendocrine cells. Sometimes, these tumors develop in the gastrointestinal tract and pancreas. Researchers want to find out if a combination of drugs can shrink these tumors. Objective: To learn if people with certain neuroendocrine tumors can take a combination of 2 drugs, Lutathera and Olaparib, without having severe side effects, and if this treatment makes the tumors shrink. Eligibility: Adults 18 and older who have a neuroendocrine tumor in the pancreas or intestine that cannot be cured by surgery and has somatostatin receptors on the cells. Design: Eligible participants will get Lutathera through an intravenous (IV) infusion every 8 weeks for 4 cycles. One cycle is 8 weeks. Each cycle includes a follow-up visit at week 4. For the IV, a small plastic tube is put into an arm vein. Participants will also take Olaparib by mouth twice a day for 4 weeks of each cycle. They will use a medicine diary to track the doses. During the study, participants will have physical exams. They will have blood and urine tests. They will fill out questionnaires about their general well-being and function. Their heart function will be tested. They will have scans of their chest, abdomen, and pelvis. One type of scan will use an IV infusion of a radioactive tracer. Participants will have a follow-up visit about 4 weeks after treatment ends. Then they will have follow-up visits every 12 weeks for 3 years. Then they will have yearly phone calls....

Type: Interventional

Start Date: Oct 2022

open study

Background: Children s weight has increased sharply in recent years. This may put them at higher risk for health problems. High blood glucose in a pregnant mother and too much weight gain during pregnancy also may have long-term effects on the child s health. Children who become overweight or obese during childhood tend to remain so as adults. Researchers want to study many risk factors during and after pregnancy, and how these affect a child s development. They will also follow the mother s health and well-being after pregnancy. Objectives: To learn how a pregnant mother s environment, lifestyle, and health conditions may affect her child s growth and development from birth until adulthood. Eligibility: American Indian/Alaska Native (AI/AN) or Hispanic adult pregnant women and their offspring. Design: Mothers will have 3 visits during pregnancy. In the child s first year, mothers will have 2 visits and their child will have 4. Children will have 2 visits in their second year and 1 each year until they turn 18. Mothers will have a visit 2 years after birth and 4-5 years later. Both the mother and child s medical records will be reviewed. They will have physical exams and give blood and stool samples. Mothers may give cord blood and placenta samples. They will give breastmilk and urine samples. They will fill out questionnaires. They will have an ultrasound. They may get an activity monitor. Mother and child will be followed until the child s 18th birthday.

Type: Observational

Start Date: Apr 2022

open study

Background: Researchers have developed a new radioactive tracer (11C-ARMI). A tracer is a drug that attaches itself to other chemicals in the body and lights up so that the chemicals can be seen in imaging scans. The new tracer may be able to help them with many diseases, such as Alzheimer s disease and Parkinson s disease. Researchers want to test the new tracer in healthy people. Objective: To test a new tracer (11C-ARMI) during imaging scans of the brain and body in healthy people. Eligibility: Healthy people aged 18 years and older. They must have been screened under protocols 01-M-0254 or 17M0181. Design: All participants will have a positron emission tomography (PET)/computed tomography (CT) scan. Before the scan, they will have blood and urine tests and a test of their heart function. The tracer will be given through a tube attached to a needle inserted into a vein in the arm. They will lie on a padded bed that fits inside a doughnut-shaped machine; the machine uses x-rays to create images of the inside of the body. Some participants will have a PET/CT scan of their whole body. They will need only 1 visit. Some participants will have a PET/CT scan of only their brain. They will have up to 2 visits. On the second visit, they will have a magnetic resonance imaging (MRI) scan of the brain. For the MRI, they will lie on a table that slides into a cylinder. The MRI uses magnetic fields to create images of the inside of the body. Participants will receive a follow-up call to check on their well-being after their PET/CT scans.

Type: Interventional

Start Date: Aug 2026

open study

Background: PDE4D is a protein in the body that plays a role in thinking and depression. This protein may play a major role in disorders such as Alzheimer disease or major depressive disorder. To learn more about these disorders, researchers want to be able to detect levels of PDE4D in the brain. 11C-JMJ-129 is a new radiotracer (a radioactive substance that highlights parts of the body during imaging scans) that was developed to attach only to PDE4D. However, early human studies showed that the tracer may break down in the body and create byproducts that interfere with the brain signal, making the results harder to interpret. This study will test whether a medication called disulfiram can improve PET imaging with 11C-JMJ-129. Disulfiram blocks an enzyme in the body that may be responsible for breaking down the tracer. By reducing this breakdown, the study aims to improve the quality and accuracy of brain images. The results may help researchers better measure PDE4D in the brain and support future studies of brain disorders. Objective: To test the new radiotracer 11C-JMJ-129, with and/or without disulfiram pretreatment during imaging scans in healthy volunteers. Eligibility: Healthy people aged 18 years and older who had a screening assessment under protocol 01-M-0254. Design: Participants will have 1 to 4 clinic visits. Participants will be screened. They will have a physical exam. They will have blood tests and a test of their heart function. Participants will undergo 1 or more of these scans: A positron emission tomography (PET) scan of the whole body. The radiotracer will be injected through a tube placed in a vein in the arm. Participants will lie on a table while a donut-shaped machine passes over them. Blood will be drawn from the arm during this scan. In Phase 5, disulfiram (500 mg orally) will be administered approximately 20 hours before the post-disulfiram PET scan A magnetic resonance imaging (MRI) scan of the brain. Participants will lie on a table that slides into a tube. A PET scan of the brain. These participants will be injected with the radiotracer. They will lie on a table with their head in the scanner. Participants will be called within 3 days after each PET scan for a check on their health.

Type: Interventional

Start Date: Apr 2025

open study

Background: Nicotine dependence leads to about 480,000 deaths every year in the United States. People with major depressive disorder (MDD) are twice as likely to use nicotine compared to the general population. They have greater withdrawal symptoms and are more likely to relapse after quitting compared with smokers without MDD. More research is needed on how nicotine affects brain function in those with MDD. Objective: To understand how nicotine affects symptoms of depression and related brain function. Eligibility: People aged 18 to 60 years, at the time of consent, with and without MDD who do not smoke cigarettes or use other nicotine products. Design: Participants will have 2 or 3 study visits over 1 year. Participants will have 2 MRI scans no less than 4 days apart. Each scan visit will last 5 to 7 hours. At each scan, they will have urine and breath tests to screen for recent use of alcohol, nicotine, and illegal drugs. Before each scan, they will take 1 of 2 medications: nicotine or placebo. Participants will receive each medication once. They will not know which medication they are receiving at each scan. For each MRI scan, they will lie on a table that slides into a cylinder. Sometimes they will be asked to lie still. Sometimes they will complete tasks on a computer. Tasks may include identifying colors or playing games to win money. Each scan will take about 2 hours. Participants will answer questions about their thoughts, feelings, and behaviors before and after each scan. They will have a blood test after each scan.

Type: Interventional

Start Date: Feb 2023

open study