Background: Human immunodeficiency virus (HIV) infects CD4 T cells. There is no cure for HIV. People with HIV need to take daily medications called antiretroviral therapy (ART) to control their infection. ART stops HIV from infecting cells, but HIV does not go away. Some infected cells remain. If ART is stopped, then HIV levels will rise and infect more cells. Objective: To compare changes in the amount of virus in blood and lymph nodes after a short treatment interruption. Eligibility: Adults aged 18 years or older who are undergoing ART for HIV infection. Design: Participants will be screened with a physical exam, including blood tests. They will be assigned to 1 of 2 groups: One group will stay on ART. They will have 2 study visits: the first 45 days after screening, and the second 12 to 16 weeks later. They will have a PET/CT scan at each visit. A substance called a tracer will be injected into their arm. They will lie still on a table that moves through a doughnut-shaped machine. This process takes up to 2 hours. The other group will stop ART for no more than 90 days. This group will have 3 PET/CT scans over 8 months. Once they stop ART, they will visit the clinic weekly for blood tests. After restarting ART, they will continue to visit the clinic weekly until their HIV level is safe. All participants will have small samples of tissue taken from lymph nodes. They may also opt to provide semen samples or vaginal fluid. They may have samples taken of bone marrow or the fluid inside their spinal column.

Type: Interventional

Start Date: Jan 2023

open study

Background: Genes are the instructions a person s body uses to function. Genome sequencing reads through all of a person s genes. Everyone has many gene variants, and most do not cause disease. Some gene variants called secondary findings may be important for a person s health even if they are not related to the reason why a person had genome sequencing done. Researchers want to learn more about what it means to have a secondary finding. Objectives: To learn about how gene variants may affect a person s health. To learn about how people understand their genetic test results. Eligibility: People with secondary findings from genetic testing done as part of a research study, clinical care, or other methods. Design: Participants may be asked to do an online survey and phone interview to ask what they think about their results, their healthcare, and if they talk with their family about the result. Eligible participants may be offered a visit to the NIH Clinical Center where they will be evaluated for health problems related to the secondary finding. DNA samples that were already collected may be studied. Participants may be asked to send in a second DNA sample (blood or saliva). These will be used to verify any findings. Participants who have a secondary finding can get genetic counseling.

Type: Observational

Start Date: Sep 2014

open study

Background: People with alcohol use disorder (AUD) also often have bouts of depression called major depressive episodes (MDEs). People having MDEs have been found to have low levels of a protein called PDE4B in the brain. Researchers want to find out if people with AUD also have low levels of PDE4B. This research may help lead to better treatments for AUD. Objective: To find out (1) if PDE4B levels are lower in people who are withdrawing from AUD and (2) if their PDE4B levels go up after they abstain from alcohol for 3 to 4 weeks. Eligibility: Adults aged 18 to 70 years with AUD. They must be enrolled in protocol 14-AA-0181. Design: Participants enrolled in protocol 14-AA-0181 will stay in the clinic for 3 to 4 weeks for alcohol withdrawal. During this stay, they will have some added procedures for the current study. Within the first week, participants will have a positron emission tomography (PET) scan of the brain. A needle will be used to guide a thin plastic tube (catheter) into a vein in one arm. An experimental substance called a radioactive tracer will be injected through the catheter. This tracer binds to PDE4B and makes it easier to see the protein in the brain. For the scan, participants will lie on a table that slides into a doughnut-shaped machine. Participants will have a second PET scan toward the end of their stay in the clinic. Participants may also have a magnetic resonance imaging (MRI) scan of the brain. They will lie on a bed that slides into a tube....

Type: Interventional

Start Date: Mar 2025

open study

Background: Alcohol use disorder (AUD) is a leading cause of disease and death worldwide. New treatments for AUD are needed. Dopamine, a chemical that carries signals between brain cells, is thought to play a role in alcohol addiction. Researchers want to learn how Suvorexant, a drug used to treat sleep disorders, affects dopamine receptors in the brain. Objective: To see how Suvorexant affects dopamine receptors in people with AUD and in healthy people. Eligibility: People aged 18 to 75 years seeking treatment for AUD. Healthy volunteers are also needed. Design: Participants with AUD will stay in the clinic for at least 10-28 days for alcohol detoxification. They will receive normal treatment for AUD. Suvorexant is a medicine used to treat sleep problem that is taken taken by mouth, once a day. Some participants will take the study drug. Others will take a placebo. The placebo looks like the study drug but does not contain any medicine. Participants will not know which they are taking. Participants will wear a device that looks like a wristwatch to track their movements during their clinic stay. Participants will have blood tests and 3 brain imaging scans before starting on the study drug: 2 positron emission tomography (PET) and 1 magnetic resonance imaging (MRI) scan. They will be injected with a radioactive tracer during each PET scan. Participants will have tests to assess their thinking, memory, and attention. They will have sleep studies. Imaging scans and other tests will be repeated at the end of the study. Healthy volunteers will have 1 MRI and 2 PET scans. They will have tests to assess of their thinking, memory, and attention. They will wear a wristwatch like movement monitor for 1 week. ...

Type: Interventional

Start Date: Nov 2024

open study

Background: People with intellectual disability (ID) often have physical disabilities as well. These physical problems can affect their bones, muscles, nerves, and gastrointestinal tracts. All of these issues can also cause pain. Yet little research has been done on pain in people with ID. Objective: To compare brain responses to unpleasant stimuli in people with and without ID. Eligibility: People aged 8 to 30 years diagnosed with an ID. Healthy volunteers without an ID are also needed. Design: The study requires only 1 visit of up to 4 hours. Participants with ID may come for up to 5 shorter visits instead. Participants will take a test to measure their level of ID. They will have a physical exam. Both groups will answer questions about pain and how their bodies react to it. They will answer questions about how they respond to things they see, feel, hear, smell, and taste. They will answer questions about their social behaviors. Caregivers may answer questions if the participant cannot. Both groups will have a test to measure their brain activity. Participants will wear a special cap, like a swim cap, with sensors and wires. Sensors to examine the heart will be placed on the skin of their chest with stickers. An elastic band will be placed around the middle of their body to measure how fast they are breathing. Sensors to measure sweat will be placed on two fingers. Participants will have heat, cold, brushing, and mild electrical stimuli to different parts of their body. Participants will rank how each stimulus feels using a scale with numbers or a scale with faces....

Type: Interventional

Start Date: Mar 2026

open study

Background: Olfactory neuroblastoma (ONB) is a rare cancer. It grows from tissue in the upper part of the nose cavity, related to the sense of smell and can affect a person s sense of smell. Researchers want to better understand the health problems of people with ONB. This may help them design better treatment and supportive care studies. Objective: To better understand ONB-the course of the disease, tumor characteristics, response to treatments, and management of the treatment. Eligibility: People ages 3 years and older who have ONB. They must enroll in NIH studies #19-C-0016 and #18-DC-0051. Design: Participants will be screened with a medical history and medical record review. Participants do not have to visit NIH. Participants will give a blood sample. They will complete surveys to assess their emotional and physical wellbeing and needs. Leftover tissue from biopsies and surgeries will be collected. Participants will take smell tests. They will smell items and answer questions about them. Participants may take taste tests. They will get plastic taste strips that they will move around their mouth to determine the taste. Participants may have a physical exam. Their performance status may be assessed. Participants may give blood, saliva, urine, and nasal secretion samples. Participants may have computed tomography and/or magnetic resonance imaging scans. Participants may have one or more tumor biopsies. Participants will talk to the research team about the results of their medical record/tests evaluation. The team will recommend how to best manage and treat their disease. Participants may give samples and complete surveys every 12 months. Their medical records will be reviewed every year. They will be monitored for the rest of their life.

Type: Observational

Start Date: Jun 2022

open study

Background: Researchers are testing version of a system known as a magnetic resonance imagining (MRI) scanner that uses strong magnetic fields, radio waves and the like to create images of the organs in the body. It uses lower energy levels than other MRI scanners. This may help scan people with metal devices in their body, or in invasive heart procedures using metal tools. Objective: To test a new MRI scanner and software changes to create better pictures. Eligibility: People with disease and healthy volunteers, ages 18 and older. Design: Participants will be screened with blood tests. Participants may have both the new MRI and a conventional MRI or only the new one. If 2 are done, they must be within 60 days. For both MRI versions, participants lie on a table that slides into a large tube. During scans, they will hold their breath for up to 20 seconds at a time. Heart activity will be measured by wires connected to pads on the skin. A flexible belt may be used to monitor their breathing. They will be in the scanner up to 2 hours. Participants can agree to have a dye called gadolinium injected into their arm during the scan. This brightens the pictures. Participants can agree to take a drug called a vasodilator. This helps detect areas of the heart with abnormal blood supply. Scans of the heart are taken before, during, and after they get the medicine. The drug may cause temporary chest pain or shortness of breath. They may get other drugs to relieve these symptoms. Sponsoring Institution: National Heart, Lung, and Blood Institute

Type: Interventional

Start Date: Jan 2018

open study

Background: Severe aplastic anemia (SAA) and myelodysplastic syndrome (MDS) are bone marrow diseases. People with these diseases usually need a bone marrow transplant. Researchers are testing ways to make stem cell transplant safer and more effective. Objective: To test if treating people with SAA or MDS with a co-infusion of blood stem cells from a family member and cord blood stem cells from an unrelated donor is safe and effective. Eligibility: Recipients ages 4-60 with SAA or MDS Donors ages 4-75 Design: Recipients will be screened with: - Blood, lung, and heart tests - Bone marrow biopsy - CT scan Recipients will have an IV line placed into a vein in the neck. Starting 11 days before the transplant they will have several chemotherapy infusions and 1 30-minute radiation dose. Recipients will get the donor cells through the IV line. They will stay in the hospital 3-4 weeks. After discharge, they will have visits: - First 3-4 months: 1-2 times weekly - Then every 6 months for 5 years Donors will be screened with: - Physical exam - Medical history - Blood tests Donors veins will be checked for suitability for stem cell collection. They may need an IV line to be placed in a thigh vein. Donors will get Filgrastim or biosimilar (G-CSF) injections daily for 5-7 days. On the last day, they will have apheresis: Blood drawn from one arm or leg runs through a machine and into the other arm or leg. This may be repeated 2 days or 2-4 weeks later.

Type: Interventional

Start Date: Jun 2017

open study

Patients with hepatic steatosis due to alcohol will be offered liver biopsies when they enter a detoxification program. The first biopsy will occur in the first week of admission and the second in the fourth week when the steatosis has resolved. The hepatic transcriptome will be compared,

Type: Observational

Start Date: Jul 2026

open study

Background: People with alcohol use disorder (AUD) often develop metabolic alcohol-associated liver disease (MetALD). MetALD is a term for the heart, liver, obesity, and other issues that can accompany AUD. MetALD can be fatal. An approved weight management drug (Tirzepatide) may be able to help people with AUD and MetALD control their alcohol intake. Objective: To test Tirzepatide in people with AUD and MetALD. Eligibility: People aged 21 years and older with AUD and MetALD. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have a test of their heart function. They will have a Fibroscan: This test uses ultrasound to measure how stiff the liver is. They will answer questions about their alcohol drinking, eating habits, and mental health. Participants may opt to have imaging scans of their brain and liver. These tests will be repeated in a baseline visit. This visit will take up to 6 hours. Tirzepatide is injected under the skin once a week for 12 weeks. Participants will visit the clinic to receive each injection. Some participants will get a placebo. A placebo is given just like a Tirzepatide injection but contains no medicine. The physical exam and other tests will be repeated during clinic visits. The Fibroscan will be repeated every 2 weeks during the study. Each weekly visit will take up to 3 hours. All tests will be repeated on the last visit. These tests will include the imaging scans and Fibroscan. Participants will learn about treatment options for AUD; they will be given recommendations on ways to reduce alcohol intake. This visit will take up to 6 hours.

Type: Interventional

Start Date: Jun 2026

open study

Background: Ollier disease (OD) and Maffucci syndrome (MS) are rare disorders that increase the risk of cancers in cartilage tissue. These tumors can lead to severe skeletal deformities beginning in childhood. People with OD or MS are also at an increased risk of blood vessel disorders and specific cancers. Researchers want to learn more about what causes these disorders. Objective: To understand the genetic causes of OD and MS. Eligibility: People aged 2 years and older who have OD or MS with cartilage tumors or blood vessel disorders. Design: Participants will stay at the NIH clinic for 5 days. They will undergo these procedures: A physical exam with blood tests. DXA (dual-energy X-ray absorptiometry) scan. The DXA scan measures the density of bones. Participants will lie on a table while a machine uses low-level X-rays to scan their body. MRI (magnetic resonance imaging) scan. An MRI uses strong magnets to take pictures of the tissues inside the body. Participants will lie on a table that slides into a large tube. A contrast dye may be injected through a needle inserted into a vein in the arm. X-rays. Some participants may have full-body X-rays instead of an MRI. X-rays take pictures of bones and other internal tissues and organs, such as the heart, lungs, and airways. PET (positron emission tomography) and CT (computed tomography) scans. Adult participants will have 2 other scans. The PET scan will include a radioactive injection into a vein. They will also have a full-body CT scan.

Type: Observational

Start Date: Jan 2025

open study

Background: Neuroendocrine neoplasms (NENs) are rare cancers in the gastrointestinal tract, pancreas, lungs, adrenal glands, and other areas of the body. Many of these cancers have a high risk of relapse and a low chance of survival. Better treatments are needed. Objective: To test a new drug, ADCT-701, in people with NENs. Eligibility: Adults aged 18 and older with NENs. Design: Participants will be screened. They will have a physical exam with blood and urine tests. They will have imaging scans and tests of heart functioning. Their ability to perform normal daily activities will be tested. A biopsy may be needed: A sample of tissue will be removed from the tumor. ADCT-701 is given through a tube attached to a needle inserted into a vein in the arm. Participants will receive the drug treatment on the first day of 21-day treatment cycles. They will visit the clinic a total of 10 times during the first two cycles. After that, they will visit the clinic 2 times during each cycle. Imaging scans, blood draws, heart function tests, and other tests will be repeated during study visits. Each visit will last up to 8 hours. Participants may continue receiving treatment with the study drug for up to 2 years. After treatment ends, participants will have follow-up clinic visits 4 times in 4 months. They will have a physical exam, with heart and blood tests, at each visit. After that, they will have follow-up clinic visits every 9 weeks; these visits will include imaging scans. Follow-up visits will continue for up to 5 years after treatment began....

Type: Interventional

Start Date: Jun 2024

open study

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 PDS01ADC 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 PDS01ADC 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.

Type: Interventional

Start Date: Feb 2021

open study

Background: Mitochondrial disease is a rare disorder. It can cause poor growth, developmental delays, muscle weakness, and other symptoms. The disease is usually inherited. It can be present at birth or develop later in life. Infection is a major cause of disease and death in people with this disease. Researchers want to learn more about these infections and the declining health of people who have this disease. To do this, researchers will study the DNA of people who become ill. Their DNA will be compared to the DNA of their household/family members. Objective: To learn more about how genes affect people with mitochondrial disease. Eligibility: People age 2 months and older with mitochondrial disease and their household/family members. .<TAB> Design: Participants will complete a questionnaire about their health history. Their medical records may be reviewed. They will give a blood sample. If the participant becomes ill, they may have a videoconference with a doctor or nurse at the NIH to perform a physical exam. They may be contacted after their illness to give updates on their health. They may be asked to give extra blood samples or complete extra questionnaires. Participants genetic data will be put into a database. The data will be labeled with a code and not their name. The data will be shared with other researchers. Participation lasts about 1 year. This may be extended if the participant is very ill.

Type: Observational

Start Date: Oct 2020

open study

Background: - Biomarkers are substances in people s blood and tissues. They help researchers understand diseases and signs of aging. Scientists want to do more research on biomarkers to find ways to improve quality of life in old age. Objective: - To learn more about biomarkers and their relationship to aging. Eligibility: - Adults at least 20 years old who weigh at least 110 pounds and have a body mass index below 30. They must agree that their genetic samples can be collected, studied, and stored. Design: - Participants will be screened with medical history, physical exam, EKG and blood and urine tests. - Participants will have 3-day visits. They will return every 2 years. - All visits include: - Blood and urine collection - Physical performance tests - Health questionnaires - Memory and problem-solving tests - Magnetic Resonance Imaging (MRI) and Computerized Tomography (CT) scans. - Muscle metabolism/ exercise tests - Taste strips - Muscle and/or skin biopsies/ red light therapy - Retinal imaging/ eye tracking - Sleep study - ODD visits also include: - Cytapheresis - Bone marrow aspirate - EVEN visits also include: - Hyperglycemic CLAMP - Lumbar Puncture (LP) - Continuous Glucose Monitor (CGM)

Type: Observational

Start Date: Mar 2015

open study

Objectives: The overall study objective is to compare the sensitivities and specificities of morphometric analysis techniques using structural MRI images based on pre- and postsurgical localization of epileptic foci in patients undergoing presurgical evaluation for medically refractory epilepsy. To carry out these analyses, we aim to establish an age-stratified normative imaging database using healthy volunteers. Additional objectives are to identify abnormal networks in these patients using resting state fMRI/EEG and MEG/EEG, and to use language and memory fMRI tasks to examine the effects of epileptogenic zones and surgery on cognitive function and the networks associated with these functions. Study population: 300 adults and children (age 8 and older) with uncontrolled focal epilepsy, and 200 age-stratified healthy volunteers. Design: A retrospective and prospective natural history study. Research procedures for patients in this study include neuropsychological testing and 1-4 MRI sessions during presurgical evaluation and an additional 1-3 MRI sessions and neuropsychological testing approximately 12 months post-operatively. Research testing (such as research neuropsychological tests or MRI scanning sequences) will be done during a visit for clinical testing whenever possible, likely reducing the number of required visits. Patients will also have optional MEG and 7T structural imaging. Data will also be obtained from patients who have already undergone epilepsy surgery if they had procedures as outlined in the protocol and are willing to share the data. Healthy volunteers will receive a subset of the pre-operative procedures for patients, requiring at least 3 visits. In order to ensure adequate data acquisition, subjects may be re-scanned up to three times for the portions of the study in which they participated, possibly requiring additional visits. Outcome measures: The main outcomes will be establishment of normative values for morphometric analysis methods in age-stratified normal controls, and comparison of the sensitivity and specificity of these measures to pre- and postsurgical localization of the epileptogenic zone. Secondary outcome measures will include determination of the sensitivity and specificity of source localization using MEG/EEG and resting state fMRI/EEG, and to evaluate changes in activation during rest, as well as language and memory fMRI tasks in patients pre- and postsurgically, to examine the effects of epileptogenic zones and surgery on cognitive function and the networks underlying these functions. ...

Type: Observational

Start Date: Mar 2014

open study

Background: Most people with hairy cell leukemia have a BRAF gene mutation. They can be treated with BRAF inhibitors, drugs that target this mutation. For people who do not have this mutation, BRAF inhibitors are not a treatment option. We found that in hairy cell leukemia, when BRAF is not mutated, the MEK gene frequently is. Binimetinib is a MEK inhibitor which targets MEK. It is important to determine if this drug can be a good treatment option in those who cannot benefit treatment with BRAF inhibitors. Objective: To see if binimetinib is an effective treatment for hairy cell leukemia that does not have a BRAF mutation. Eligibility: People ages 18 and older with hairy cell leukemia without a mutation in the BRAF gene and whose disease either did not respond to treatment or came back after treatment Design: Participants will be screened with: - Medical history - Physical exam - Blood and urine tests - Lung and heart tests - Eye exam - Bone marrow biopsy: A needle will be injected through the participant s skin into the bone to remove a sample of marrow. - CT or MRI scan: Participants will lie in a machine that takes pictures of the body. They might receive a contrast agent by vein. Before they start treatment, participants will have an abdominal ultrasound, pulmonary function tests, and exercise stress tests. Participants will take binimetinib by mouth twice daily in 28-day cycles. They will keep a medication diary. Participants will have at least one visit before every cycle. Visits will include repeats of some screening tests. Participants may continue treatment as long as their disease does not get worse and they do not have bad side effects. About a month after their last dose of treatment, participants will have a follow-up visit. They will then have visits once a year....

Type: Interventional

Start Date: Jan 2021

open study

Background: - Researchers are interested in studying individuals who have known or suspected metabolic, inflammatory or genetic diseases that may put them at a high risk for heart diseases or diseases of their blood vessels. Depending on the condition being studied, both affected and nonaffected individuals may be asked to provide blood and other samples and may undergo tests to evaluate the heart, blood vessels and lung function. The testing is tailored to the individual and/or condition being studied. Nonaffected individuals may include relatives of affected individuals and healthy nonrelated volunteers. Objectives: - To study individuals who have or are at risk for cardiovascular diseases, and in some cases their unaffected relatives and healthy volunteers. Eligibility: - Individuals between 1 and 100 years of age. Participants may be healthy volunteers, individuals with cardiovascular diseases, or unaffected relatives of individuals with cardiovascular diseases. Design: - Participants will have some or all of the following tests, as directed by the study researchers: - Photography of the face and full body - Body measurements - Radiography, including chest or limb x-rays - Metabolic stress testing to study heart and muscle function - Echocardiography to study heart function - Magnetic resonance imaging (MRI) studies, including cardiovascular MRI, angiography, and contrast MRI, to study heart function and performance - Computed tomography (CT) angiogram to obtain images of the heart and lungs - Positron emission tomography (PET) imaging to study possible fat infiltration of the heart - Six-minute walk test to study heart, lung, and muscle function and performance - Vascular ultrasound to study blood vessel walls - Blood, tissue, and other specimens will be collected for research and testing, and will be taken either as part of the clinical study or during surgical procedures. - Follow-up studies may be performed under separate research protocols.

Type: Observational

Start Date: Jul 2010

open study

Background: Autoimmune lymphoproliferative syndrome (ALPS) is a rare disorder of the immune system caused by a mutation in the FAS gene. In ALPS, the body stores too many germ-fighting cells called lymphocytes. This can lead to an enlarged spleen and lymph nodes. Current treatments for ALPS can have many adverse effects. Better treatments for ALPS are needed. Objective: To test a study drug (soquelitinib) in people with ALPS. Eligibility: People aged 16 years and older with ALPS. Design: Participants will have 8 clinic visits and 6 remote visits within 1 year. Participants will be screened. They will have a physical exam with blood and urine tests. Some may have tests of their lung function. Soquelitinib is a tablet taken by mouth twice a day. Participants will record their doses and any symptoms on a paper or online form. Blood tests and other procedures will be repeated during study visits. Three visits will include imaging scans. Participants will lie on a table that slides through a doughnut-shaped machine while X-rays capture pictures of the inside of their body. Some participants may be able to remain in the study for a second year.

Type: Interventional

Start Date: Mar 2025

open study

Background: Laboratory tests that use blood and urine can provide a great deal of information about human health and disease. To develop even better tests and to improve the ways samples are handled for testing researchers need to experiment with samples from healthy people. Objective: This natural history study will collect blood and urine from healthy people. The samples will build a repository that will be used for all kinds of research. Eligibility: Healthy people aged 18 years or older. Design: Participants will have 1 study visit. The visit will last up to 2 hours. Participants will be screened. They will answer questions about their health history. They will list any medications they take. They will consent to donate samples for research and future use: Blood: Up to 4.5 tablespoons of blood may be collected from a needle inserted into a vein. Urine: Participants will be given a sterile container to provide a sample. Some participants may be asked to provide other types of samples. Some participants may be asked to provide new samples if their first ones are depleted.

Type: Observational

Start Date: Jul 2024

open study

Background: The National Cancer Institute, part of the National Institutes of Health, has partnered with nine health care systems across the U.S. to establish the Connect for Cancer Prevention Study. While researchers have made important discoveries, there is more to learn to lower the number of people affected by cancer. By taking part in Connect, participants can help researchers learn how the way we live, our genetics, and our health history may affect cancer risk. Objective: To study and better understand the causes of cancer and to find new ways to prevent it. Eligibility: The study will include 200,000 adults who get their health care from a partner health care system, are between 30 and 70 years old at enrollment, and have never had cancer. People remain eligible to join if they have or once had non-melanoma skin cancer, or a condition that may raise cancer risk (such as ductal carcinoma in situ, or DCIS). Design: Eligible recruits can sign up for Connect online by creating an account on MyConnect using their email address or phone number. After creating an account, they will complete the informed consent process. All information shared through MyConnect is secure to protect participant privacy. After joining the study, participants will be asked to answer online health surveys a few times a year, donate samples of blood, urine, and saliva every two to three years, and safely share access to their electronic health records with Connect. In the future, participants may donate unused samples that are collected at clinical visits, like tissue, stool, or blood, and may mail in samples collected at home. Participants may also share information from personal health trackers, like wearable devices or apps. This information will help researchers study the health and behavior patterns that may affect cancer risk. It takes time to understand the causes of cancer, so Connect will go on for many years. The longer people participate, the more researchers may learn. Participants can leave the study at any time. Learn more about Connect by visiting cancer.gov/connectstudy.

Type: Observational

Start Date: Jul 2021

open study

Background: - Li-Fraumeni syndrome (LFS) is a genetic condition that increases the risk for some types of cancer. LFS may lead to cancer of the bone or connective tissue, breast, and brain. It may also increase the risk for certain types of leukemia and other cancers. The only known cause of LFS is a change (called a mutation ) in a gene known as TP53. However, not all people with LFS have a TP53 mutation. Researchers want to study other possible genetic causes of LFS, and factors that may increase or decrease cancer risk in people with the syndrome. Objectives: - To learn more about the types of cancers that occur in individuals with LFS. - To study the role of the TP53 gene in the development of cancer. - To look for other possible genes that cause LFS - To study the effect of LFS diagnosis on families. - To determine if environmental factors or other genes can change a person s cancer risk associated with LFS. Eligibility: - Individuals with a family or personal medical history of cancers consistent with LFS. - Individuals with a family or personal medical history of cancers that does not meet the diagnosis of LFS, but the history is suggestive for LFS (meets the diagnosis for the so-called Li-Fraumeni like syndrome) - Individuals with certain rare cancers - Individuals with a family or personal history of a TP53 gene mutation, with or without related cancer(s). Design: - Participants will fill out a medical history questionnaire and a family history questionnaire. - Blood samples will be collected for DNA and for storage. Cheek cell samples may be collected if blood cannot be obtained for DNA. Participants can choose to have or not have cancer screening with blood tests, imaging studies, and other exams. - Participants will complete questionnaires about their worries about cancer, stress levels, and coping strategies. Diet and physical activity questionnaires will also be given. Other psychological tests may be given as needed. - Participants will be monitored for several years, with regular followup visits to the National Institutes of Health, if indicated. Any changes in health or cancer status will be recorded.

Type: Observational

Start Date: Jan 2012

open study

This study will examine the natural history of Leishmanial infections and their treatments. It will provide an opportunity for NIAID staff to learn more about leishmaniasis and perhaps to improve diagnostic tests for these infections. Patients between 2 and 80 years of age with known or suspected leishmaniasis are eligible for this study. Participants will have routine blood tests and a biopsy to confirm leishmanial infection. The biopsy procedure will be determined by the type of infection local cutaneous leishmaniasis (LCL), mucocutaneous leishmaniasis (MCL) or visceral leishmaniasis (VL). CL will be confirmed with a punch biopsy, in which a cookie-cutter type razor is used to remove a small circular piece of skin tissue. MCL will be confirmed using a thin flexible tube inserted into the nose. This tube is used to examine the nose and upper airway and to remove a tissue sample, if an affected area is seen. VL will be confirmed with either a bone marrow or liver biopsy or a splenic aspirate. For these procedures, a small tissue sample is withdrawn through a needle placed in the hipbone, liver or spleen, respectively. Some patients may also have a skin test for leishmaniasis similar to tuberculin skin testing. Treatment and length of hospital stay are determined by the type of infection. CL may be treated with Pentostam, amphotericin, amphotericin B, itraconazole or ketoconazole; ML with amphotericin B, or encapsulated amphotericin; and VL with Pentostam or encapsulated amphotericin. Pentostam is infused daily for 18 to 28 doses, most as an outpatient. Blood is drawn 3 times a week for safety tests and an electrocardiogram is done 2 to 3 times a week to monitor heart rhythm. Amphotericin B is infused every day or every other day for about 30 doses, all on an inpatient basis. Patients undergo hydration (infusion of a large amount of fluid) just before and immediately after each infusion to protect the kidneys. Blood is drawn every other day and urine samples are collected occasionally for routine urinalysis. Encapsulated amphotericin is infused every other day, on an outpatient basis. Blood is generally drawn every other day to every 2 days and urinalyses are done periodically. Itraconazole and ketoconazole are taken orally for at least 1 to 3 months, with blood drawn every 2 to 3 weeks. Patients may be asked to have photographs taken before, during and after treatment to document progress. They may also be asked to provide extra blood samples for research purposes, either through a vein in the arm or through apheresis, a method for collecting large numbers of cells. For apheresis, whole blood is collected through a needle in an arm vein and circulated through a machine that separates it into its components. The desired cells are then removed, and the rest of the blood is returned to the body, either through the same needle used to draw the blood or through a second needle in the other arm. Patients with cutaneous leishmaniasis will have a follow-up clinic visit 2 weeks to 3 months after treatment is completed. If there are no complications, their participation will end at that time. Patients with mucocutaneous leishmaniasis and visceral leishmaniasis will be followed every 3 to 6 months indefinitely for routine evaluations and re-treatment if the infection recurs.

Type: Observational

Start Date: Nov 2001

open study

BACKGROUND: - A number of important scientific advances can be made through the study of blood, bone marrow, tumor, or other tissue samples from patients with HIV infection, infection with Kaposi s sarcoma associated herpesvirus (KSHV), infection with other oncogenic viruses, or cancer. - This protocol provides a mechanism to affect a variety of such studies. OBJECTIVES: -Acquisition of serum, circulating cells, bone marrow, and tumor or normal tissue samples from participants with HIV infection, KSHV infection, or with cancer. ELIGIBILITY: -Eligibility criteria include age 18 years or older and at least one of the following: Exposure risk to HIV, KSHV, or HPV; HIV seropositive; KSHV seropositive; EBV seropositive; HTLV-1 seropositive; malignancy, Castleman s disease, or skin lesions with appearance of Kaposi s sarcoma; or cervical or anal intraepithelial lesion. DESIGN: - Up to 999 subjects will be enrolled in this study. - Blood samples may be collected at the initial visit, and at follow-up visits. - Other fluids/excretions may be collected (such as urine, saliva, semen, and stool). - Tumor samples may be obtained by fine needle aspirate, by removal of pleural or peritoneal fluid, by skin punch biopsy, or by excisional biopsy, providing the tumor is accessible with minimal risk to the participants. - Specific risks will be described in a separate consent to be obtained at the time of the biopsy. - Samples will be studied in the HIV and AIDS Malignancy Branch, CCR, NCI; laboratories in NCI-Frederick; or those of collaborating investigators.

Type: Observational

Start Date: Dec 2000

open study

Background: Many cancers of the testicles and urinary tract are rare diseases; these are diseases that affect less than 200,000 people in the United States. It can be hard to study treatments for these diseases. One combination of drugs-enfortumab vedotin (EV) and pembrolizumab-has already been approved to treat some urinary cancers. Researchers want to see if they can help people with other types of testicle and urinary cancers. Objective: To test EV, with or without pembrolizumab, in patients with rarer cancers of the testicles or urinary tract. Eligibility: People aged 18 and older with rarer cancers of the testicles or urinary tract. Design: Participants will be screened. They will have a physical exam with blood and urine tests. Their ability to perform normal daily activities will be tested. They will have exams of their skin and eyes. They will have imaging scans. A biopsy may be needed: A sample of tissue will be removed from the tumor. The study drugs are both given through a tube attached to a needle inserted into a vein in the arm. Some participants will receive treatments 3 times during 28-week cycles; others will receive treatments 2 times during 21-day cycles. All participants may continue to receive treatments for up to 5 years. Imaging scans and other tests will be repeated. Participants who stop taking the drugs will have follow-up visits every 3 to 4 weeks until the disease gets worse. They will have imaging scans and blood tests. After that, follow-up visits will continue by phone every 3 months for up to 5 years after study therapy is finished.

Type: Interventional

Start Date: Jan 2026

open study