40 Clinical Trials for Various Conditions
Common variable immunodeficiency (CVID) is the most prevalent symptomatic primary immunodeficiency. Respiratory ailments are the most frequent complications of CVID, with chronic pulmonary disease developing in 30-60% and even more experiencing frequent acute respiratory infections. This project aims to establish cutting-edge approaches to study pulmonary biology in CVID and apply novel bioinformatics strategies to study complex interactions among microbes and host cells by direct sampling of the respiratory tract. The central hypothesis for this research is that antibody (Ab) deficiency in CVID alters respiratory microbiota and host interactions to drive pulmonary disease.
This study will determine whether an experimental medicine, STA-5326 mesylate, is safe to use in patients with common variable immunodeficiency (CVID) who have inflammation of the gut. It will also determine if patients who take this drug show improvement in their symptoms, decrease in inflammatory chemicals in the gut, changes in their immune cells, and improvement in how their gut is functioning to absorb food. Patients between 18 and 75 years of age with CVID and chronic diarrhea or involuntary weight loss of more than 5 percent of their past body weight over the past 12 months may be eligible for this study. Candidates are screened with a review of their medical records, a medical history and physical examination, blood, urine and stool tests, chest x-rays and skin test for exposure to tuberculosis, and a hydrogen breath test. For the latter, breath samples are collected before and every 20 minutes (for 2 hours) after the subject drinks a sugar solution. This test determines the digestive effects of bacteria in the upper intestine. Samples are collected by having the subject blow into a balloon. Participants undergo the following tests and procedures: Immune System and Gastrointestinal Evaluation * 48-hour stool fat collection (measures the amount of undigested fat in the stool): Subjects keep a diary of what they eat for a 48-hour period. At the beginning of the 48 hours they take two dye capsules and then take another two capsules 48 hours later. They collect a stool sample when they pass the second set of capsules in their bowel movement. An additional 24-hour stool collection is tested for loss of protein in the stool. * D-xylose absorption test (measures the ability of the gut to absorb nutrients): Subjects drink a solution of d-xylose (a sugar substitute). Blood samples are collected before and 1 hour after drinking the solution. * Upper endoscopy: A thin flexible lighted tube is advanced through the mouth to evaluate the esophagus, stomach and beginning of the small intestine. * Lower endoscopy: A thin flexible lighted tube is advanced through the rectum to evaluate the colon. Treatment Period (Study days 1 to 57) * Physical examination - study days 1, 8, 15, 29, 43 and 57 * Blood samples to test the levels of STA-5326 in the blood. On study days 1 and 57, samples are collected before the medication dose and 1, 2, 4, 6 and 8 hours after the dose; on day 29, one sample is collected before the medication dose. * Blood samples for routine safety testing - study days 1, 8, 15, 29, 43 and 57 * Medication history - study days 1, 8, 15, 29, 43 and 57 * Interview about pain, discomfort, and well being - study days 1, 8, 15, 29, 43 and 57 * Pregnancy test for women who can become pregnant - study days 15, 43, and 57 * D-xylose absorption test - study days 29 and 57 * Electrocardiogram - study days 29 and 57 * Urine test - study days 29 and 57 * Blood test for research on immune cells - study day 57 * Repeat endoscopies and studies of gut function (24- and 48-hour stool collections) Follow-up period (Day 85 and day 113) -Physical examination, blood tests, medication history, questions about pain, discomfort and well being
This study aims to understand the causes and progression of Common Variable Immunodeficiency (CVID) and related inborn errors of immunity (IEI). These are conditions where the immune system does not function properly, leading to frequent infections and other complications such as gastrointestinal inflammation, lung and liver disease, autoimmune conditions, and an increased risk of certain cancers. By studying patients with CVI and related immune disorders, we hope to develop better ways to diagnose, treat, and prevent complications associated with these conditions. Patients diagnosed with CVID or related immune disorders must be referred by their physician and medical records reviewed by the study team to confirm eligibility to participate in this study. Once enrolled, participants will undergo various tests, including blood draws, physical exams, and imaging studies like CT scans to track changes over time. We may collect samples such as blood, urine, stool, or saliva for research purposes. If a surgical procedure or biopsy is performed because it is medically necessary, we may collect an additional sample for research testing. Family members of patients may be asked to provide blood samples for comparison. Some tests may be done remotely if participants or family members cannot travel to the study site. Who Can Participate * Patients diagnosed with CVI or related IEI, such as X-linked agammaglobulinemia, Blau Syndrome or Yao Syndrome. * Participants must be at least 2 years old. * Family members of patients may include parents, siblings, grandparents, children, aunts, uncles, and cousins. * Pregnant women already enrolled in the study will continue to participate, but new pregnant participants will not be enrolled. Potential Risks and Benefits * Risks: Blood draws may cause discomfort, bruising, or infection. Apheresis may cause dizziness, nausea, or muscle cramps; this procedure is to collect specific cells in the blood and is infrequently done on this protocol. Extra biopsies during clinically indicated procedures may increase the risk of complications; they will only be collected after the medically necessary biopsies are taken and if it is safe to collect any extra biopsies. * Benefits: Participants may not receive direct medical benefits, but the study will contribute to a better understanding of CVID and related conditions, potentially leading to improved treatments.
In this study, common variable immunodeficiency (CVID) patients will all receive the study drug, leniolisib, for a treatment period of 6 months. Participants will start on a lower dose of leniolisib, followed by a mid and then a higher dose level. The primary goal is to assess the safety and tolerability of leniolisib, and secondary goal is to assess the potential for leniolisib to provide benefits for patients.
The purpose of this study is to determine if the supplement, Fisetin, can be used as a treatment option for common variable immunodeficiency (CVID) by comparing its efficacy to placebo.
Although there is evidence in the literature that gammaglobulin replacement therapy can lead to a reduction in the prevalence of pulmonary infection and improved lung function, there is no published study to guide immunologists regarding the use of spirometry in titrating IG therapy to assist in the management of immunodeficiency patients with regards to gammaglobulin replacement therapy. The investigators propose to study the use of spirometry to identify patients that could potentially benefit from an increase in IGRT. The investigators will identify 22 common variable immune deficiency (CVID) study subjects on stable IGRT replacement therapy equivalent to 0.40 to 0.60 gm/kg per 4 weeks who have evidence of mild to moderate obstruction as assessed by an FEF25-75% between 50% and 80% of predicted. Patients who are on Hizentra will be preferentially recruited. Of these 22, 11 will be identified at random and treated for 6 months at their current dose (control population). The remaining 11 study subjects (treatment group) will have their level of IGRT increased by the equivalent of 0.05 gm/kg in dose per 4 weeks, adjusted for bioavailability as per manufacturer's instructions. On average, rounded up to the nearest gram, this will typically increase their dose of Hizentra by 2 gm per week.
There is no standard of care therapy for patients with granulomatous-lymphocytic interstitial lung disease (GLILD) seen in common variable immunodeficiency (CVID). Abatacept has recently looked promising for the treatment of patients with complex CVID. This study is a multi-site, phase II, randomized, blinded/placebo-controlled clinical trial in pediatric and adult subjects to determine the efficacy of abatacept compared to placebo for treatment of subjects with GLILD in the context of CVID. Funding Source - FDA OOPD
This is an observational, case-control study with a single blood draw among two cohorts, patients with antibody deficiency (e.g., CVID) and healthy controls. Samples will be analyzed by mass cytometry (CyTOF) to examine the major signaling pathways of all circulating innate and adaptive immune cell types, as well as whole exome sequencing. The goal is to improve our general understanding of the human immune response to infections and the diagnosis of CVID.
Background: - Some people with Common Variable Immunodeficiency Disease (CVID) have gastrointestinal inflammation. This can cause diarrhea, weight loss, and not being able to absorb nutrition from food. Researchers want to see if the drug ustekinumab can help these problems. This drug blocks some proteins that cause inflammation. Objective: - To test the safety and efficacy of the drug ustekinumab for people with CVID with gastrointestinal inflammation. Eligibility: - Adults ages 18-75 with CVID. They must have chronic diarrhea, have unintentionally lost weight in the last year, and/or need to use nutritional supplements to maintain their weight. Design: Participants will undergo the following screening studies to make sure that this study is a good fit for your medical situation, and to make sure it is safe for you to receive the study medications tests, including tests for HIV and hepatitis . This will be done as an inpatient at the NIH Clinical Center and takes about 5-6 days: * Participants will be screened with: * Medical history * Physical exam * Blood tests, including tests for HIV and hepatitis. * Stool tests, including a timed 48 hour collection for fat malabsorption and a 24 hour collection for protein malabsorption * Urine tests, including a pregnancy test for any women with the ability to have a child * Chest CT scan to look for infection * D-xylose testing, which involves drinking a sugary solution and then having a blood sample drawn to test carbohydrate (sugar) malabsorption * Hydrogen breath testing for test for small intestinal bacterial overgrowth (SIBO) this test also involves drinking a sugary solution and then collecting breath samples * Upper endoscopy (EGD) and/or colonoscopy to look at the lining of the GI tract and take biopsies for testing. This will be done under sedation by a qualified gastroenterologist. Participants who complete screening and meet all criteria will then return to the NIH Clinical Center for the following visits: * First Treatment Visit (1 clinic day): Medical history, physical exam, measurement of vital signs and weight, review of medications, and an assessment of number and consistency of stools each day. A pregnancy test for women of childbearing potential. A nurse will give you three shots of 90 mg ustekinumab (270 mg total dose) by very small needles injected under the skin, and then observe you for 1 hour. * Week 8 Treatment Visit (1 clinic day): Medical history, physical exam, measurement of vital signs and weight, review of medications, and an assessment of number and consistency of stools each day. Blood, urine and stool samples will be collected. A pregnancy test for women of childbearing potential. A nurse will give you one 90 mg dose of ustekinumab by a very small needle injected under the skin, and then observe you for 1 hour. * Week 16 Treatment Visit (1 clinic day): Medical history, physical exam, measurement of vital signs and weight, review of medications, and an assessment of number and consistency of stools each day. Blood, urine and stool samples will be collected. A pregnancy test for women of childbearing potential. A nurse will give you one 90 mg dose of ustekinumab by a very small needle injected under the skin, and then observe you for 1 hour. * Week 24 Treatment and Mid-point Evaluation Visit (4-6 inpatient days): Medical history, physical exam, measurement of vital signs and weight, review of medications, and an assessment of number and consistency of stools each day. Blood, urine and stool samples will be collected, including repeating the d-xylose carbohydrate malabsorption testing, the 24 hour stool collection for protein malabsorption and the 48 hour stool collection for fat malabsorption. A pregnancy test for women of childbearing potential. A nurse will give you one 90 mg dose of ustekinumab by a very small needle injected under the skin, and then observe you for 1 hour. * Week 32 Treatment Visit: Medical history, physical exam, measurement of vital signs and weight, review of medications, and an assessment of number and consistency of stools each day. Blood, urine and stool samples will be collected. A pregnancy test for women of childbearing potential. A nurse will give you one 90 mg dose of ustekinumab by a very small needle injected under the skin, and then observe you for 1 hour. * Week 40 Treatment Visit: Medical history, physical exam, measurement of vital signs and weight, review of medications, and an assessment of number and consistency of stools each day. Blood, urine and stool samples will be collected. A pregnancy test for women of childbearing potential. A nurse will give you one 90 mg dose of ustekinumab by a very small needle injected under the skin, and then observe you for 1 hour. * Week 48 ...
This study will determine whether people with common variable immunodeficiency (CVID) with and without gastrointestinal (GI) symptoms have gut abnormalities (inflammation or loss of function) and changes in immune system cells and chemicals in the blood and gut. People with CVID have decreased levels of serum immunoglobulin IgG and IgA. Patients have sinus, lung and other infections, and many also have stomach and intestinal problems, such as chronic diarrhea, inability to absorb nutrition from food, and intestinal infections caused by bacteria. CVID patients with gastrointestinal symptoms 10 years of age and older may be eligible for this study; CVID patients without gastrointestinal symptoms 18 years of age and older will be enrolled as control subjects. Candidates will be screened with a review of their medical records, a medical history and physical examination, HIV blood test, stool sample, and hydrogen breath test. The breath test measures the amount of hydrogen in the breath after drinking sugar water, showing the digestive effects of bacteria in the upper intestine. Participants will be admitted to the NIH Clinical Center for several days to undergo the following procedures: * Medical history and physical examination * Blood tests * Urine and stool samples * 48-hour stool fat collection measures the amount of undigested fat in the stool to determine the ability of the gut to digest and absorb fat in the diet * D-Xylose absorption test measures the ability of a sugar compound to travel across the lining of the intestine to determine the ability of the gut to absorb nutrients * Upper endoscopy a thin flexible lighted tube is advanced through the mouth to evaluate the esophagus, stomach and beginning of the small intestine * Lower endoscopy a thin lighted tube is advanced through the rectum to evaluate the colon Identification of GI abnormalities associated with changes in immune response in CVID patients will help in developing and testing new treatments for this disease.
Patients receiving intravenous immunoglobulin (IVIG) therapy for primary immunodeficiency and neurologic conditions may experience adverse drug reactions (ADRs). The mechanism of the ADR is unknown. Currently, the standard practice for these patients is to change from IV to subcutaneous IG (SCIG) but because of the need of immunomodulation or patient preference, SCIG may not be an option. Data has shown that some levels of complement decrease from pre- to post-infusion of IVIG. This study is to determine if replacing this complement protein may ameliorate ADRs.
Recommendations concerning the administration of Zostavax® in patients with antibody deficiency are unclear. The investigators plan to assess the immunogenicity and safety of Zostavax® in patients with antibody deficiency as compared with healthy volunteers.
This study was designed to explore CDZ173, a selective PI3Kδ inhibitor, in patients with genetically activated PI3Kδ, i.e., patients with Activated phosphoinositide 3-kinase delta syndrome/ p110δ-activating mutation causing senescent T cells, lymphadenopathy and immunodeficiency (APDS/PASLI). The study consisted of two parts: Part I was the open label part designed to establish the safety and pharmacokinetics of CDZ173 in the target population, as well as to select the optimal dose to be tested in Part II. Part II was designed to assess efficacy and safety of CDZ173 in the target population.
The goal of our study is to assess the cellular immune responses of participants with antibody deficiency disease before and after immunization with SARS-CoV-2 mRNA vaccines.
Background: During a transplant, blood stem cells from one person are given to someone else. The cells grow into the different cells that make up the immune system. This can cure people with certain immunodeficiencies. But transplant has many risks and complications. Objective: To see if stem cell transplant can be successfully performed in people with primary immunodeficiency disease and cure them. Eligibility: People ages 4-69 for whom a primary immunodeficiency (PID) or Primary Immune Regulatory Disorder (PIRD), has caused significant health problems and either standard management has not worked or there are no standard management options, along with their donors Design: Donors will be screened under protocol 01-C-0129. They will donate blood or bone marrow. Participants will be screened with: Medical history Physical exam Blood, urine, and heart tests CT or PET scans Before transplant, participants will have dental and eye exams. They will have a bone marrow biopsy. For this, a needle will be inserted through the skin into the pelvis to remove marrow. Participants will be hospitalized before their transplant. They will have a central catheter put into a vein in their chest or neck. They will get medications through the catheter to prevent complications. Participants will get stem cells through the catheter. They will stay in the hospital for at least 4 weeks. They will give blood, urine, bone marrow, and stool samples. They may need blood transfusions. They may need more scans. They will take more medications. Participants will have visits on days 30, 60, 100, 180, and 360, and 24 months after the transplant. Then they will have visits once a year for about 5 years
Researchers are trying to determine if withdrawal of budesonide therapy in patients with immune-mediated enteropathies doing well on therapy will result in worsening symptoms, histology, quality of life, and micronutrient/nutritional status when compared to continued therapy.
Background: Blood stem cells in the bone marrow make all the cells to normally defend a body against disease. Allogeneic blood or marrow transplant is when these stem cells are transferred from one person to another. Researchers think this treatment can provide a new, healthy immune system to correct T-cell problems in some people. Objective: To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with T-cell problems. Eligibility: Donors: Healthy people ages 4 and older Recipients: People the same age with abnormal T-cell function causing health problems Design: All participants will be screened with: * Medical history * Physical exam * Blood, heart, and urine tests Donors will also have an electrocardiogram and chest x-ray. They may have veins tested or a pre-anesthesia test. Recipients will also have lung tests. Some participants will have scans and/or bone marrow collected by needle in the hip bones. Donors will learn about medicines and activities to avoid and repeat some screening tests. Some donors will stay in the hospital overnight and have bone marrow collected with anesthesia. Other donors will get shots for several days to stimulate cells. They will have blood removed by plastic tube (IV) in an arm vein. A machine will remove stem cells and return the rest of the blood to the other arm. Recipients will have: * More bone marrow and a small fragment of bone removed * Dental, diet, and social worker consultations * Scans * Chemotherapy and antibody therapy for 2 weeks * Catheter inserted in a chest or neck vein to receive donor stem cells * A hospital stay for several weeks with more medicines and procedures * Multiple follow-up visits...
In this study, the investigators test 2 dose levels of thiotepa (5 mg/kg and 10 mg/kg) added to the backbone of targeted reduced dose IV busulfan, fludarabine and rabbit anti-thymocyte globulin (rATG) to determine the minimum effective dose required for reliable engraftment for subjects undergoing hematopoietic stem cell transplantation for non-malignant disease.
This aim of this research project is to determine if low to moderate level exercise can have an impact on stress, fatigue, and quality of life for individuals diagnosed with a primary immunodeficiency disease. This 8-week study will compare participants engaging in a semi-customized, home exercise program (exercise intervention group) to participants performing normal activities (non-exercise control group). This study will track stress, fatigue, and quality of life in individuals with a diagnosis of primary immunodeficiency disease, using standardized questionnaires, journals, and interviews.
Background: People who have certain immune system diseases often need a procedure called allo HSCT. This is short for allogeneic hematopoietic stem cell transplant. This might cure people with these diseases. Many people who need allo HSCT need donors who are relatives with similar genes. But the disease may also affect those in the donor pool. This may mean there are fewer options for people with inherited diseases. Researchers want to collect data on how transplant candidates and their donors are found. Objective: To find out how genetic diseases and the ways they are inherited affect the breadth of options for allo HSCT donors. Eligibility: Records from studies that have already been done. These will be for people ages 4 and older who were evaluated for allo HSCT or to be donors. Design: Participants already signed a consent form for their records to be shared. Researchers will study the participant data. Data will be stored in an electronic system. Researchers will use passwords to protect the data.
Background: Allogeneic blood or marrow transplant is when stem cells are taken from one person s blood or bone marrow and given to another person. Researchers think this may help people with immune system problems. Objective: To see if allogeneic blood or bone marrow transplant is safe and effective in treating people with primary immunodeficiencies. Eligibility: Donors: Healthy people ages 4 or older Recipients: People ages 4-75 with a primary immunodeficiency that may be treated with allogeneic blood or marrow transplant Design: Participants will be screened with medical history, physical exam, and blood tests. Participants will have urine tests, EKG, and chest x-ray. Donors will have: Bone marrow harvest: With anesthesia, marrow is taken by a needle in the hipbone. OR Blood collection: They will have several drug injections over 5-7 days. Blood is taken by IV in one arm, circulates through a machine to remove stem cells, and returned by IV in the other arm. Possible vein assessment or pre-anesthesia evaluation Recipients will have: Lung test, heart tests, radiology scans, CT scans, and dental exam Possible tissue biopsies or lumbar puncture Bone marrow and a small piece of bone removed by needle in the hipbone. Chemotherapy 1-2 weeks before transplant day Donor stem cell donation through a catheter put into a vein in the chest or neck Several-week hospital stay. They will take medications and may need blood transfusions and additional procedures. After discharge, recipients will: Remain near the clinic for about 3 months. They will have weekly visits and may require hospital readmission. Have multiple follow-up visits to the clinic in the first 6 months, and less frequently for at least 5 years.
The primary objective is to demonstrate the bioequivalence of Gammaplex® 10 intravenous immunoglobulin (IGIV) and Gammaplex® 5% IGIV with respect to area under the curve within a 28-day dosing interval (AUC0-28) in a cohort of adult subjects. The secondary objectives are to demonstrate the bioequivalence of Gammaplex® 10 IGIV and Gammaplex® 5% IGIV with respect to area under the curve within a 21-day dosing interval (AUC0-21) in adult subjects; to assess the pharmacokinetics of Gammaplex 10 IGIV and Gammaplex 5% IGIV including Immunoglobulin G (IgG) trough levels and to investigate the safety and tolerability of Gammaplex 10 IGIV and Gammaplex 5% IGIV in adults subjects; to assess the pharmacokinetics of Gammaplex 10 IGIV including IgG trough levels and to investigate the safety and tolerability of Gammaplex 10 IGIV in pediatric subjects.
The main objective of the study is to determine the pharmacokinetics profile of Subgam-VF. The secondary objectives are to assess the safety of Subgam-VF and refine the dose adjustment coefficient for Subgam-VF needed for subjects switching from prior intravenous immunoglobulin (IGIV) therapy.
The purpose of this study is to determine whether bilateral orthotopic lung transplantation (BOLT) followed by cadaveric partially-matched hematopoietic stem cell transplantation (HSCT) is safe and effective for patients aged 5-45 years with primary immunodeficiency (PID) and end-stage lung disease.
This study hypothesizes that a reduced intensity immunosuppressive preparative regimen will establish engraftment of donor hematopoietic cells with acceptable early and delayed toxicity in patients with immune function disorders. A regimen that maximizes host immune suppression is expected to reduce graft rejection and optimize donor cell engraftment.
This is a standard of care treatment guideline for allogeneic hematopoetic stem cell transplant (HSCT) in patients with primary immune deficiencies.
The main objective is to determine the efficacy of Gammaplex by measuring the number of serious acute bacterial infections during treatment with Gammaplex over a 12 month period. The secondary objectives are to assess the safety and tolerability of Gammaplex and to compare the data collected from adult subjects with PID from the GMX01 study
Background: * Bronchiectasis is a disease characterized by airways that are inflamed, abnormally dilated, and chronically infected. Individuals with bronchiectasis have a history of chronic and recurring respiratory infections. Depending on the underlying cause, these infections may involve the entire respiratory tract, resulting in sinus, ear, and lung disease. * Bronchiectasis continues to be a significant problem in developing countries and in specific groups of individuals, particularly in people who have cystic fibrosis. Although treatments are available or under development for bronchiectasis related to cystic fibrosis, many of the disease-specific treatments may not be effective for bronchiectasis not related to cystic fibrosis. Objectives: - To study the natural history of bronchiectasis to identify inherited and immune factors that may explain why certain individuals have chronic recurring infections. Eligibility: * Individuals 5 years of age and older who have an established diagnosis of bronchiectasis or a history of chronic/recurring respiratory infections. * Direct family members (e.g., parents, siblings, children) of patients in the study may also be asked to participate. Design: * Potential participants will be screened with an initial clinic evaluation and full medical history, as well as a general quality of life and respiratory symptom questionnaire. * The following standard procedures may be done as part of the study: air sampling from the nose; imaging studies, which may include an x-ray or computed tomography (CT), lung function tests; and collection of samples of blood, urine, and sputum (phlegm or mucus). Other tests may be performed as required by the researchers, and will be explained to patients as needed. * Both patients and relatives (if asked to participate) will provide the following samples: blood or buccal (cheek swab) cells for genetic testing, sputum, and urine. * To prevent infections and potential disease progression, patients may receive standard medical care and treatment for bronchiectasis and related infections during this protocol.
The objectives of this trial are the assessment of safety and efficacy of IgPro10 in patients with PID, and the assessment of tolerability of high infusion rates. To demonstrate safety, the number of infusions temporally associated with AEs, the rate, severity and relationship of all AEs and the vital sign changes during each infusion will be evaluated.
The main objective of this study is to see if GAMMAPLEX is efficacious with respect to Food and Drug Administration (FDA) minimal requirements (no more than 1 serious, acute, bacterial infection per subject per year) in subjects with Primary Immunodeficiency Diseases (PID). The secondary objectives are to assess the safety and tolerability of GAMMAPLEX and to determine if GAMMAPLEX has a pharmacokinetic (PK) profile comparable with that of intact Immunoglobulin G (IgG) in subjects with PID.