All Clinical Trials

This protocol will evaluate patients with systemic lupus erythematosus (SLE) and their relatives to learn more about how the disease develops and changes over time. It will also study genetic factors that make a person susceptible to SLE. Patients 3 years of age and older with known or suspected SLE and their relatives may be eligible for this study. Patients will be evaluated with a medical history and physical examination, blood and urine tests. Other procedures may include: 1. Electrocardiogram 2. 24-hour urine collection 3. Imaging studies, such as chest and joint X-rays, magnetic resonance imaging (MRI) scans, bone scans, and bone densitometry. 4. Questionnaire about the degree of disease activity, and survey of risk factors for disease complications. 5. Apheresis-Collection of plasma (fluid portion of blood) or blood cells for analysis. Whole blood is collected through a needle in an arm vein. The blood circulates through a machine that separates it into its components. The required component (plasma or cells) is removed and the rest of the blood is returned to the body through the same needle or through a second needle in the other arm. 6. Skin biopsy-Removal of a small skin sample for microscopic analysis. An area of skin is numbed with an anesthetic and a small circular portion (about 1/4 inch in diameter) is removed, using a sharp cookie cutter-type instrument. 7. Kidney, bone marrow or other organ biopsy-Removal of a small sample of organ tissue. These biopsies are done only if they can provide information useful in better understanding the disease or making treatment decisions. 8. Genetic studies-Collection of a blood sample for gene testing. Patients will be followed at least once a year with a brief history and physical examination and routine blood and urine tests. Some patients may be seen more often. Treatment recommendations will be offered to patients' physicians, and patients who are eligible for other research treatment studies will be invited to enroll. Participating relatives of patients will fill out a brief medical history questionnaire and provide a DNA sample (either a blood sample or tissue swab from the inside of the cheek) for genetic testing.... Read Less

The Hyper IgE Syndromes (HIES) are primary immunodeficiencies resulting in eczema and recurrent skin and lung infections. Autosomal dominant Hyper IgE syndrome (AD-HIIES; Job's syndrome) is caused by STAT3 mutations, and is a multi-system disorder with skeletal, vascular, and connective tissue manifestations. Understanding how STAT3 mutations cause these diverse clinical manifestations is critical to our complete understanding of bone metabolism, bronchiectasis, dental maturation, and atherosclerosis. Bi-allelic mutations in DOCK8 cause a combined immunodeficiency previously described as autosomal-recessive Hyper IgE syndrome. These individuals suffer from extensive viral infections as well as have a high incidence of malignancy and mortality. The pathogenesis of this disease and long-term natural history is being investigated. Therefore, we seek to enroll patients and families with a confirmed or suspected diagnosis of HIES syndrome for extensive phenotypic and genotypic study as well as disease management. Patients will be carefully examined by a multidisciplinary team and followed longitudinally. Through these studies we hope to better characterize the clinical presentation of STAT3-mutated HIES, DOCK8 deficiency and other causes of the hyper IgE phenotype, and to be able to identify further genetic etiologies, as well as understand the pathogenesis of HIES. We seek to enroll 300 patients and 300 relatives.... Read Less

Purpose: The purpose of this protocol is 1. To comprehensively evaluate patients with autoinflammatory diseases clinically, genetically and immunologically at the autoinflammatory disease clinic at the NIH. 2. To follow patients with autoinflammatory Diseases that are genetically defined including Neonatal-Onset Multisystem Inflammatory Disease (NOMID), the most severe clinical phenotype of Cryopyrin-Associated Periodic Syndromes (CAPS), Deficiency of IL-1 Receptor Antagonist (DIRA), Chronic Atypical Neutrophilic Dermatosis with Lipodystrophy and Elevated temperatures (CANDLE), and STING-Associated Vasculopathy with onset in Infancy (SAVI), and those with genetically undefined autoinflammatory disorders to determine long-term disease outcomes. 3. To develop biomarkers that help us assess disease activity and response to treatment. 4. To assess the eligibility of affected patients for inclusion in ongoing and planned treatment protocols. Goal: The goals of our studies are to understand the underlying immune dysregulation, to identify the genetic cause and to translate our findings into novel treatments that improve patients disease outcome. Eligibility: * Patients with known NOMID/CAPS, DIRA, CANDLE, SAVI, CRMO, Still's Disease, and with other yet undifferentiated autoinflammatory diseases. * Healthy adult and pediatric relatives. * Volunteers Design: Participants will be evaluated at the NIH for 2-5 days. All participants will have a detailed medical history, physical exam, blood tests and other evaluations depending on the extend of their autoinflammatory disease. Participants may also expect the following assessments: 1. Clinical test that help assess organ damage and functional impact such as hearing vision, memory and learning tests. 2. Imaging studies to characterize the organ involvement of the inflammatory disease including: X-rays, CT scans, special MRIs, bone scans. 3. Laboratory evaluations including clinical markers of disease activity, research samples for genetic studies, and blood samples for cytokine/biomarker assessment, and gene expression profiling.\<TAB\> 4. Completion of questionnaires to assess disease activity and quality of life. 5. If indicated, other procedures may be administered that include: a lumbar puncture if CNS inflammation is suspected and a skin biopsy if skin inflammation is present. other gastrointestinal procedures as they are clinically indicated. 6. Patients my have a research skin biopsy taken. Participants may return for a single follow-up visits or for long term-follow up depending on their disease and willingness to be followed long-term. ... Read Less

This study will determine the biochemical and genetic causes of inherited immune diseases affecting lymphocyte homeostasis. Lymphocytes are a type of white blood cell that fights infections. Normally, the body keeps a precise balance in which lymphocyte growth is matched by lymphocyte death. People with constantly enlarged lymph nodes or spleen, along with autoimmune disease, immunodeficiency, lymphoma, or other immune problems affecting lymphocytes may have an abnormality of the immune system in the cell growth and cell death processes that regulate lymphocyte homeostasis. Patients who have, or are suspected of having, an inherited lymphocyte homeostasis or programmed cell death susceptibility syndrome may be eligible for this study. Relatives of patients are also included. Participants' (patients and relatives) medical records are reviewed and blood samples are drawn for studies to identify genes involved in immune disorders. Tissues that have been removed from patients for medical reasons, such as biopsied tissues, may be examined for tissue and DNA studies. Relatives are studied to determine if some of them may have a very mild form of lymphocyte homeostasis disorder. Patients who have an immune problem that the researchers wish to study further will be invited to donate additional blood samples at irregular intervals (at least once a year) and to provide an update of their medical records at the same time. Read Less

Objective With this prospective natural experiment trial on neurofibromatosis type 2 (NF2) study, we hope to understand the factors leading to tumor progression and neurological disease burden in NF2. Study Population A total of 269 participants, ages 8-75, with a clinical or genetic diagnosis of NF2 will participate in this study. Design Study participants will be evaluated with a thorough physical and neurologic examination upon enrollment. This initial outpatient evaluation will include magnetic resonance imaging with contrast of brain and spine and blood collection for research use. Participants with measurable hearing will have audiology assessment performed. Participants with untreated vestibular schwannomas will have vestibular assessment performed during the initial visit. Genetic studies performed outside will be acceptable as confirmation of NF2 in enrolled patients. If needed to confirm NF2 with genetic studies, or for research purpose, whole genome/whole exome sequencing may be performed on blood obtained from subjects enrolled in this study. All participants will be evaluated by a speech language pathologist. Subjects will be followed as outpatients for up to ten years, during which clinical, and radiologic evaluation will be performed annually. Auditory testing will be performed annually for participants with measurable hearing. Participants with initially untreated vestibular schwannomas will be followed annually with vestibular testing. Speech and swallowing reassessments will be repeated if worsening of speech or swallowing is reported. Blood will be collected at each visit for blood biomarker testing Outcome measures We hope to understand the biologic basis for speech and swallowing dysfunction in patients with NF2. We will study and report the strength of association of MRI findings, clinical assessments cranial nerve deficits and speech/swallowing dysfunction. We hope to identify imaging biomarkers of hearing loss in NF2. We will attempt to discover the mode of peripheral neuropathy in patients with NF2. Lastly, we will attempt to discover previously unknown serum biomarkers associated with high tumor burden in NF2. Read Less

Background: - Previous studies have shown that people with certain types of brain damage may have particular problems paying attention and processing things that they see. Researchers are interested in comparing how people with brain damage and without brain damage process visual images. Objectives: - To better understand the areas of the brain involved in paying attention to things that are seen. Eligibility: - Individuals at least 18 years of age who either have had damage to one or both sides of specific parts of the brain (e.g., stroke, injury, certain neurosurgery procedures) or are healthy volunteers. Design: * The study involves 4 to 10 visits to the NIH Clinical Center over 1 to 2 years. Each visit will last approximately 2 hours. * Participants will be screened with a medical history and physical examination, and may have the cognitive testing described below during the same visit. * On the first visit and for at least one visit thereafter, participants will have cognitive testing to evaluate thinking and memory. These tests will be either written tests or computer-based tests. * Some participants will qualify for functional magnetic resonance imaging (fMRI) as part of the study. This part will involve a decision-making task that will be performed on a computer during the fMRI scan. Additional scans may be required as directed by the study doctors. * Some randomly selected participants will be asked to have magnetoencephalography (MEG), a procedure to record very small magnetic field changes produced by brain activity. * During the behavioral training, or fMRI or MEG scanning, participants may be monitored with equipment to track eye movements. Read Less

Background: - KSHV inflammatory cytokine syndrome (KICS) is a newly recognized disease caused by Kaposi sarcoma-associated herpesvirus (KSHV). This virus can cause cancer. People with KICS can have severe symptoms. They include fever, weight loss, and fluid in the legs or abdomen. People with KICS may also be at risk of getting other cancers associated with KSHV. These cancers include Kaposi sarcoma and lymphoma. Because KICS is a newly identified disease, more information is needed on how the disease works and what can be done to treat it. Objectives: - To collect genetic and medical information from people with KSHV inflammatory cytokine syndrome. Eligibility: - Individuals at least 18 years of age who have Kaposi sarcoma herpes virus and symptoms that resemble those caused by KICS. Design: * Participants will have regular study visits. The schedule will be determined by the study researchers. * Participants will provide a complete medical history and have a full physical exam. Blood and urine samples will be collected as well. * People with KICS that requires treatment may get new experimental treatments. These treatments may include antiviral drugs and chemotherapy drugs, depending on the nature of the disease. * Participants will have imaging studies, such as chest x-rays and computed tomography scans, to study the tumors. * Bone marrow and lymph node biopsies may be done to collect tissue samples for study. * Participants who have Kaposi sarcoma will have photographs taken of their lesions. Read Less

Background: - Asthma is a lung condition that causes difficulty breathing and decreased lung function. Some people with asthma have more severe disease symptoms. They may be less responsive to standard treatments such as steroids. Researchers want to compare severe asthmatics with mild or moderate asthmatics or people without asthma over a long period. This information may help identify new treatments for people whose asthma is not well controlled by standard medications. Objectives: - To compare severe asthmatics with mild or moderate asthmatics, and healthy volunteers, to study the progression and outcomes of the disease. Eligibility: * Individuals at least 18 years of age who have been diagnosed with asthma for at least 1 year. * Healthy volunteers at least 18 years of age. Design: * This study will involve an initial visit to the NIH Clinical Center for all participants. Selected participants may be asked to return for repeat visits over a number of years. The test results from participants with asthma will be compared with those from the healthy volunteers. * All participants will be screened with a physical exam and medical history. * Participants may (but will not necessarily) have the following tests at each visit: * Complete medical history and physical exam * Blood, urine, sputum, and nasal cell samples * Breath tests and heart and lung function tests * Six-minute walk test to measure ability to exercise * Imaging studies such as chest x-rays, bone density scans, and sinus scans * Allergy skin testing * Vocal cord exam * Overnight sleep study * Participants may remain on the study for as long as they are willing to participate and do not develop health problems that will interfere with the study. Read Less

Background: - Researchers want to develop better ways to treat cancer. In this study, they will give people with cancer two drugs. These drugs have been used on their own to treat some blood cell cancers. Objectives: - To test the safety and efficacy of the drug combination of bortezomib and clofarabine. Eligibility: - Adults age 18 and over with advanced cancer that has progressed after receiving standard treatment or that has no effective therapy. Design: * Participants will be screened with medical history, physical exam, and scans to measure their tumors. They will also have heart, blood, and urine tests. All of these may be done by their regular doctors. * Participants will get the study drugs in 21-day cyles. They will stay at the clinic for week 1 of every cycle, then have 2 weeks off. \<TAB\>- Bortezomib will be injected under the skin on days 1 and 4. \<TAB\>- Clofarabine will be injected in a vein for days 1-5. * During cycle 1 only, participants will go to the clinic or their doctor to have a physical exam and blood tests at the start of the second and third week. * Participants will have clinical evaluations throughout the study, including before receiving treatment and then before the start of each cycle. * Participants may stay in the study as long as they are tolerating the drugs and their tumor is not getting worse. * Participants will have follow-up for 30 days after the last dose of study drugs. * The first part of this study tests the safety of different doses of clofarabine and bortezomib. * The second part of this study involves a separate group of participants who will undergo mandatory research biopsies to learn more about the effects of clofarabine and bortezomib on cancer cells.... Read Less

Background: Some patients with unusual genetic conditions are referred to the National Institutes of Health (NIH). They may not be eligible to join current research studies. Testing such patients is a good way to improve the skills of research staff. The findings could lead to new processes and research. Objectives: To recruit a diverse group of pediatric subjects with genetic disorders. To give clinic staff hands-on experience working with these patients. Eligibility: Children any age with a known or suspected genetic disorder. Design: Participants will be screened with medical history and physical exam. They may have lab and other tests. Family members may give DNA samples. Participants will have: Medical history Physical exam Height, weight, and other measurements taken. A clinical evaluation of their disorder. They may have: Blood, urine, and saliva samples taken Imaging tests. These may include x-rays, scans, ultrasound, or skeletal survey. A sleep study A visit with other specialists at NIH A genetic test from a commercial lab Medical photographs taken Other tests Participants may have follow-up visits. They may get medical or surgical treatment. Read Less

Background: People with addictions often find it hard to choose the long-term benefits of abstinence over the short-term effects of using drugs. Researchers think this is partly due to parts of the brain involved in certain types of learning and decision-making. Researchers want to test these basic functions using a simple task with pictures and odors. Objective: To see if performance in a learning task differs between people who have opioid-use disorder and people who don t. Eligibility: Adults 21-60 years old who are willing to fast for at least 6 hours and smell food odors. Those with an opioid-use disorder must either not use for at least 3 weeks or be in treatment. Design: Participants will have 1 visit that will take up to 5 hours. Before the visit, participants will be asked to not eat or drink anything except water for at least 6 hours. At the visit, participants will be checked for signs of intoxication. Participants will give urine and breath samples. Participants will have tests of learning and behavior. They will look at shapes on a computer screen. The shapes will be paired with different food odors. The odors will come from a sterile tube placed under the nose. Participants will have their breathing monitored with a belt around the upper abdomen. About 30 days and 60 days later, participants will be called and asked about their drug use over the past 30 days. Read Less

This phase II trial studies the effect of lutetium Lu 177 dotatate compared to the usual treatment (everolimus) in treating patients with somatostatin receptor positive bronchial neuroendocrine tumors that have spread to other places in the body (advanced). Lutetium Lu 177-dotate is a radioactive drug. It binds to a protein called somatostatin receptor, which is found on some neuroendocrine tumor cells. Lutetium Lu 177-dotatate builds up in these cells and gives off radiation that may kill them. It is a type of radioconjugate and a type of somatostatin analog. Lutetium Lu 177 dotatate may be more effective than everolimus in shrinking or stabilizing advanced bronchial neuroendocrine tumors. Read Less