View clinical trials related to Granulomatous Disease, Chronic.
Filter by:"Kineret" (INN: Anakinra) neutralizes the biological activity of interleukin-1α (IL-1α) and interleukin-1β (IL-1β) by the concurrent inhibition of binding to interleukin-1 receptor I (IL-1RI). Interleukin-1 (IL-1) is the main pro-inflammatory cytokine that mediates many cellular responses. Anakinra inhibits the reactions caused by IL-1 in vitro, including the induction of nitric oxide and prostaglandin E2 and / or the formation of collagenase by synovial cells, fibroblasts and chondrocytes. According to published data, patients with the chronic granulomatous disease have an increased secretion of interleukin-1, which contributes to the development of granulomatous inflammation. Blocking interleukin-1 reduces the activity of the main pro-inflammatory complex - the inflammasomes, and also restores the autophagy process impaired in patients with chronic granulomatous disease. In this way, inhibition of the IL-1 receptor prevents the activation of innate immunity cells and prevents the maintenance of pathological pro-inflammatory signaling in conditions of IL-1 overproduction. The efficacy and safety of therapy with the above drug is based on the results of international studies on the using of anakinra in patients with chronic granulomatous disease.
The overall goal of the study is to investigate the functional, biochemical, and gene expression effects of Interferon-gamma 1-b (IFN-γ) on the neutrophils of patients with Chronic Granulomatous Disease (CGD). The investigators hypothesize that the clinical effects demonstrated in patients with CGD treated with IFN-γ (decreased number and severity of infections) are the result of biochemical processes and upregulation of specific genes, which lead to enhanced functionality of this immune cell population.
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.
The investigators hypothesize that neutrophils and monocytes developed under the influence of Interferon- gamma-1b (IFN-γ-1b, Actimmune*) in vivo will display enhanced function across a broad range of activities related in large part to the transcriptional activation effects of this cytokine. The investigators will evaluate the effects of IFN-γ in healthy human subjects in vivo on gene expression, biologic activity markers, and functional activity of myeloid cells in single dose studies and in steady state studies.
Many genetic diseases of lymphohematopoietic cells (such as sickle cell anemia, thalassemia, Diamond-Blackfan anemia, Combined Immune Deficiency (CID), Wiskott-Aldrich syndrome, chronic granulomatous disease, X-linked lymphoproliferative disease, and metabolic diseases affecting hematopoiesis) are sublethal diseases caused by mutations that adversely affect the development or function of different types of blood cells. Although pathophysiologically diverse, these genetic diseases share a similar clinical course of significant progressive morbidity, overall poor quality of life, and ultimate death from complications of the disease or its palliative treatment. Supportive care for these diseases includes chronic transfusion, iron chelation, and surgery (splenectomy or cholecystectomy) for the hemoglobinopathies; prophylactic antibiotics, intravenous immunoglobulin, and immunomodulator therapies for the immune deficiencies; and enzyme replacement injections and dietary restriction for some of the metabolic diseases. The suboptimal results of such supportive care measures have led to efforts to implement more aggressive therapeutic interventions to cure these lymphohematopoietic diseases. The most logical strategies for cure of these diseases have been either replacement of the patient's own hematopoietic stem cells (HSC) with those derived from a normal donor allogeneic bone marrow transplant (BMT) or hematopoietic stem cell transplant (HSCT), or to genetically modify the patient's own stem cells to replace the defective gene (gene therapy).
Background: People who get chronic illnesses as children are living longer. When they turn 18, they switch from pediatric care to adult care. This can be a difficult change. Chronic Granulomatous Disease (CGD) is an inherited disease. It causes long-term, repeated infections. People with CGD are usually diagnosed when they are very young children. Researchers want to find out more about how young people with CGD handle the change to adult care. What they learn may make this easier for people with CGD in the future. Objective: - To identify what helped or hurt young adults with CGD as they went from pediatric to adult care. Eligibility: - Adults with CGD who were 18 24 years old between January 2011 and February 2014. Design: - Participants will already be enrolled in NIH studies. - Eligible people will get materials in the mail. They will get a letter with study information, an interview questionnaire, and an information sheet. - Researchers will call participants 1 week after the packets are sent. They will talk about the study and find out if the person wants to join. - An interview will be completed immediately or scheduled for the future. The interview will take about 45 minutes. The researcher will ask the participant about their disease. They will also ask about travel to NIH, being an outpatient or inpatient there, and legal documents. - Researchers may contact the subjects again by phone if they need more information at any point during the study.
This study is a longitudinal and cross-sectional evaluation of patients with Chronic Granulomatous Disease (CGD) who received or are receiving hematopoietic cell transplantation (HCT) for their disease under a variety of protocols used by participating institutions compared to a control non-HCT group receiving standard care. Investigators at multiple centers caring for patients with CGD in North America and 3 centers in Europe will participate. Patients with CGD will have been treated according to institutional practice and protocols. Investigators will enroll these patients as subjects in this protocol. This study will investigate which patients benefit most from HCT, and what types of transplants are optimal for patients with CGD, in the context of overall outcomes in CGD patients with and without transplant.
HLH, HLH-related disorders, Chronic Granulomatous (CGD), HIGM1, Immune dysregulation, polyendocrinopathy, enteropathy, and X-linked inheritance (IPEX) and severe LAD-I represent primary immune disorders that are typically fatal without Hematopoietic Cell Transplant (HCT). However, transplant is often complicated by inflammation, infection and other co-morbidities. In addition, these disorders have been shown to be cured with partial chimerism, making them an ideal target for the use of reduced intensity approaches, where a portion of patients may not achieve full donor chimerism, but instead achieve stable mixed chimerism. Reduced-intensity conditioning strategies have demonstrated improved survival with decreased Treatment Related Mortality (TRM) in institutional series for patients with HLH (Cooper et al., 2006; Marsh et al., 2010; Marsh et al., 2011). However, graft loss and unstable chimerism remain challenges. An institutional case series from Cincinnati Children's Hospital demonstrated full or high-level chimerism and improved durable engraftment using intermediate (Day -14) timing alemtuzumab (Marsh et al., 2013b). This study aims to test the efficacy of the Intermediate RIC strategy in a prospective multi-center study including HLH as well as other primary immunodeficiencies where allogeneic transplant with RIC has been shown to be feasible and stable chimerism is curative.
This is a single arm, phase I study to assess the tolerability of abatacept when combined with cyclosporine and mycophenolate mofetil as graft versus host disease prophylaxis in children undergoing unrelated hematopoietic stem cell transplant for serious non-malignant diseases as well as to assess the immunological effects of abatacept. Participants will be followed for 2 years.
Background: - Atherosclerosis, the arterial plaques or blockages that cause heart disease, develops in many people by the time they are in their mid-20s. The rate of atherosclerosis in patients with immune system disorders has not been well studied, but it may be very different from the general population. - Patients with chronic granulomatous disease (CGD) produce less of a group of molecules known as free radicals, which help to fight infection and may play a role in the development of atherosclerosis. Patients with CGD may develop atherosclerosis much more slowly than people without CGD. On the other hand, carrier mothers of children with genetically-linked CGD often have problems with autoimmune problems in addition to a problem with making free radicals. Patients with other immune system disorders also have very different responses to infection, and many of them also have autoimmune-like problems that may change the risk of developing atherosclerosis. Objectives: - To study the prevalence of atherosclerosis in patients with immune system disorders, compared with healthy individuals. Eligibility: - Individuals at least 18 years of age who either have been diagnosed with an immune system disorder or are healthy volunteers. Design: - The active part of the study involves one or two visits to the National Institutes of Health Clinical Center for a series of imaging tests and scans. - Participants will have the following tests during the active part of the study: - (1) CAT scan to obtain images of the chest arteries and measure the amount of calcium in the artery walls. - (2) Magnetic resonance imaging scan to obtain images of the coronary and carotid arteries in the chest and neck. - (3) Electrocardiogram to provide data on current heart function. - (4) Blood samples to provide data on heart, kidney, and immune system function. - Participants will be contacted every 2 years in the future for up to 30 years to determine whether they have developed heart disease. Researchers will ask participants to provide contact information for two other people who may likely know how to get in touch with the participant in the future.