View clinical trials related to Chronic Granulomatous Disease.
Filter by:This study is for patients with chronic granulomatous disease (CGD), which is a disorder of the immune system that puts them at risk for severe infections. CGD is caused by a genetic defect that stops or prevents the white blood cells from killing certain bacteria and fungi. This condition cannot presently be cured by standard treatment with drugs or surgery. Medicine including antibiotics, antifungals, and interferon gamma, may help some patients with CGD; however even with continuous treatment, most patients with CGD will have chronic and recurrent infections. Transfusion of white blood cells may help overcome infection, but white cell transfusions lead to allergic reactions and fever and the benefit of transfusion lasts only a matter of hours. Ultimately, chronic infections can damage or injure the body organs. Injury to the lung or liver can lead to lung or liver failure and death. Medicines used to treat infection can damage body organs too. Infections may become resistant to antibiotic or antifungal treatment, and infections not responding to treatment can be deadly. It is now known that under specific conditions and with special treatment, blood stem cells (the cells that make blood) can be transplanted from one person to another. Stem cell transplantation has been done for patients with CGD who have a healthy sibling and who share the same immune type (HLA type) as the patient. Stem cell transplantation allows healthy or normal white cells from the stem cell donor to grow or develop in the patient's bone marrow. These healthy white cells can fight infection and prevent future infections for a patient with CGD. Patients on this study will receive stem cells from a related or unrelated donor. The donor will be closely matched to the patient's immune type but the donor is not a sibling. The reason this treatment is investigational is that we do not know the likelihood of benefit that the patient will receive. It is possible that they will have great benefit, like some of the patients who have been transplanted from a brother or sister. It is possible that the side-effects of treatment may be too severe so that the transplant won't work. The purpose of this research study is to evaluate whether or not patients with CGD treated with a stem cell transplant from a non-matched and/or non-related donor can have a good outcome from the procedure with an acceptable number of side-effects.
Healthy volunteers and patients with diseases that involve problems clearing mucus from the lungs will be examined and tested to better understand the reasons for recurring lung infections in these patients and to try to develop better ways to diagnose and treat them. The study will also try to identify the genes responsible for these diseases. Healthy volunteers 18 years of age and older and patients 2 years of age or older with suspected primary ciliary dyskinesia (PCD), variant cystic fibrosis (CF) or pseudohypoaldosteronism (PHA) may be eligible for this study. Patients enrolled in the Natural History Study of Nontuberculous Mycobacteria at NIH or other NIH natural history protocols may also be enrolled. Participants undergo the following tests and procedures during a 1-day visit at the NIH Clinical Center, as follows: All patients and normal volunteers have the following procedures: - Physical examination and review of medical and genetic history and family genetic history. - Lung function test and measurement of oxygen saturation level. - Nitric oxide measurement to measure the amount of nitric oxide production in the nose: A small tube is placed in the nose while the subject breathes through the mouth into a cardboard tube. All patients have the following additional procedures: - Blood tests for liver and kidney function, blood count, immunoglobulins and pregnancy test (where appropriate). - Blood test or buccal scrape (brushing the inside of the cheek) to obtain DNA to look for gene mutations that cause PCD, CF or PHA. - Scrape biopsy of cell lining the inside of the nose: A small toothpick-sized plastic stick with a tiny cup on the end is used to get nasal lining cells to look at the cilia (hair-like structures that move mucus). - Semen analysis (in some men) to test sperm tail function or structure. Patients suspected of having a variant of CF or PHA, including nontuberculous mycobacterial lung disease, have the following additional procedures: - Sweat chloride test: A medicine is placed on the arm to produce sweat; then, a very low level of electric current is applied for 5 to 12 minutes. Sweat is collected in a plastic tube and tested for salt content. - Blood draw for CF genetic testing, if necessary, and to measure levels of the enzyme trypsin. - Saliva collection to measure sodium and chloride content. - Nasal potential difference to measure the electrical activity of the cells lining the inside of the nose: A soft plastic tube filled with a salt solution is passed into the nasal passage and a sterile needle is placed under the skin of the arm. This test provides information about how the lining of the nose is able to get used to changes in temperature and humidity. (Normal volunteers also have this test.)
This study will compare the health and well being of children treated with a modified stem cell transplantation procedure for chronic granulomatous disease (CGD) with that of children receiving standard of care treatment. CGD is an inherited disorder of neutrophils-a type of infection-fighting white blood cell-that leaves patients vulnerable to life-threatening infections. Standard treatment with antibiotics, and sometimes surgery, is not always successful, and patients with persisting infections have a poor long-term prognosis. Transplantation of donated stem cells (cells produced by the bone marrow that mature into white and red blood cells and platelets) can improve immune function in patients with CGD and possibly cure the disease. However, this procedure carries a significant risk of death, because it requires complete suppression of the immune system with high-dose chemotherapy. In addition, lymphocytes-another type of infection-fighting white blood cell-from the donor may cause what is called graft versus host disease (GvHD), in which the donor cells 'see' patient's cells as foreign and mount an immune response to reject them. To try to reduce these risks, patients in this study will be given low-dose chemotherapy that is easier for the body to tolerate and involves a shorter period of complete immune suppression. Also, the donor's lymphocytes will be removed from the rest of the stem cells to be transplanted, reducing the risk of GvHD. Patients with CGD between 2 and 17 years of age who 1) are currently free of active infection, and 2) have a history of at least one life-threatening infection or a family member with CGD and a history of at least one life-threatening infection, and 3) a family member that is a suitable donor may be eligible for this study. Candidates will have a medical history, physical examination and blood tests, lung and heart function tests, x-rays or CT scans of the body, and dental and eye examinations. They will fill out questionnaires that measure emotional well being, quality of life, and intelligence (ability to learn and understand). Stem cells will be collected from both the patient and donor. To do this, the hormone G-CSF will be injected under the skin for several days to move stem cells from the bone marrow to the bloodstream. Then, the stem cells will be collected by apheresis. In this procedure the blood is drawn through a needle placed in one arm and pumped into a machine where the required cells are separated out and removed. Then, the rest of the blood is returned through a needle in the other arm. Several days before the transplant procedure, patients will start a 'conditioning regimen' of chemotherapy with cyclophosphamide, fludarabine and Campath 1H. When the conditioning therapy is completed, the donor's stem cells will be infused. To help prevent rejection of donor cells, cyclosporine will be given by mouth or by vein starting 1 month after the transplant procedure. The average hospital stay for stem cell transplantation is 21 days. After discharge, patients will return to the NIH clinic for follow-up clinic visits weekly or twice weekly for 2 to 3 months. These visits will include a symptom check, physical examination and blood tests. Subsequent clinic visits will be scheduled 1 to 3 times a year for at least 5 years.
This study will investigate the safety and effectiveness of a new stem cell transplant procedure for treating chronic granulomatous disease (CGD) in patients with active infection. CGD is an inherited disorder of neutrophils-a type of infection-fighting white blood cell-that leaves patients vulnerable to life-threatening infections. Standard treatment with antibiotics, and sometimes surgery, is not always successful, and patients with persisting infections have a poor long-term prognosis. Transplantation of donated stem cells (cells produced by the bone marrow that mature into the different blood components-white cells, red cells and platelets) can cure CGD. However, this procedure carries a significant risk of death, particularly in patients with active infection, because it requires completely suppressing the immune system with high-dose chemotherapy and radiation. In addition, lymphocytes-another type of infection-fighting white blood cell-from the donor may cause what is called graft vs. host disease (GvHD), in which the donor cells "see" patient's cells as "foreign" and mount an immune response to reject them. To try to reduce these risks, patients in this study will be given low-dose chemotherapy and no radiation, a regimen that is easier for the body to tolerate and involves a shorter period of complete immune suppression. Also, the donor's lymphocytes will be removed from the rest of the stem cells to be transplanted, reducing the risk of GvHD. Patients with CGD between the ages of age 1 and 55 years old who have an active non-viral infection may be eligible for this study. They will have a medical history, physical examination and blood tests (including testing for adequacy of the genetic match with the donor). A bone marrow sample will be taken to evaluate disease status. This test, done under a local anesthetic, uses a special needle to draw out bone marrow from the hipbone. A central venous catheter (flexible plastic tube placed in a vein) will be put in place before treatment begins. It will be used to draw and transfuse blood, give medications, and infuse the donated stem cells. Several days before the transplant procedure, patients will start low-dose chemotherapy with cyclophosphamide and fludarabine, two commonly used anti-cancer drugs. They will also be given anti-thymocyte globulin to prevent rejection of the donated cells. When this conditioning therapy is completed, the stem cells will be infused through the central line. Patients will be given cyclosporine 4 days before and 3 months after the stem cell transplant to help prevent rejection. About 3 weeks after the transplant, patients will be discharged from the hospital. They will return for follow-up clinic visits weekly and then twice weekly for 3 months. These visits will include a symptom check, physical examination, and blood tests. Blood transfusions will be given if needed. Subsequent visits will be scheduled at 4, 6, 12, 18, 24, 30 and 36 months after the transplant, or more often if required, and then yearly.
This study will try to determine what causes learning, behavioral and emotional problems in children with chronic granulomatous disease (GCD) and other phagocyte disorders. (Phagocytes are a type of white blood cell.) Children with these disorders have frequent severe infections that require hospitalization, sometimes for long periods of time. Many of them also have problems with school, learning, behavior, anxiety and depression. This study will explore whether these latter problems are a direct result of the illness itself or are a consequence of frequent, long hospitalizations, or are due to other factors. Test findings in these children will be compared with those of children with cystic fibrosis-another disease that causes frequent infections requiring prolonged hospitalization. Patients age 2 or older with GCD or other phagocytic disorders or cystic fibrosis may be eligible for this study. Participants (or a parent or guardian) will complete questionnaires including personal information such as age, gender and marital status, a family medical history, and information on their illness. Patients will be given various psychological and intelligence tests, and they and their parents or guardians will be interviewed by a child psychiatrist. The tests and interviews take a total of about 5 hours and are given in two or three separate sessions. The tests may reveal problems such as learning disorders, attention-deficit hyperactivity disorder, anxiety, or depression. If any of these problems are identified, appropriate referrals will be made for specialized services, such as special school placement, tutoring, or counseling.
This study will investigate the safety and effectiveness of a modified stem cell transplant procedure for treating chronic granulomatous disease (CGD) in patients with active infection. CGD is an inherited disorder of neutrophils-a type of infection-fighting white blood cell-that leaves patients vulnerable to life-threatening infections. Transplantation of donated stem cells (cells produced by the bone marrow that mature into the different blood components-white cells, red cells and platelets) can cure CGD. However, this procedure carries a significant risk of death, particularly in patients with active infection, because it requires completely suppressing the immune system with high-dose chemotherapy and radiation. In addition, lymphocytes-another type of infection-fighting white blood cell-from the donor may cause what is called graft vs. host disease (GvHD), in which the donor cells recognize the patient's cells as foreign and mount an immune response to destroy them. To try to reduce these risks, patients in this study will be given low-dose chemotherapy and no radiation, a regimen that is easier for the body to tolerate and involves a shorter period of complete immune suppression. Also, the donor's lymphocytes will be removed from the rest of the stem cells to be transplanted, reducing the risk of GvHD. Patients with CGD between the ages of age 1 and 55 years old who do not have an active infection and who have a family member that is a well matched donor may be eligible for this study. Candidates will have a medical history, physical examination and blood tests, lung and heart function tests, X-rays of the chest and sinuses, and dental and eye examinations. A bone marrow sample may be taken to evaluate disease status. This test, done under a local anesthetic, uses a special needle to draw bone marrow from the hipbone. Stem cells will be collected from both the patient and donor. To do this, the hormone G-CSF will be injected under the skin for several days to increase stem cell production. Then, the stem cells will be collected by apheresis. In this procedure the blood is drawn through a needle placed in one arm, pumped into a machine where the desired cells are separated out and removed, and then the rest of the blood is returned through a needle in the other arm. A large plastic tube (central venous line) is placed into a major vein. It can stay in the body and be used the entire treatment period to deliver the donated stem cells, give chemotherapy or other medications, including antibiotics and blood transfusions, if needed, and withdraw blood samples. Several days before the transplant procedure, patients will start low-dose chemotherapy with cyclophosphamide and fludarabine, two commonly used anti-cancer drugs. They will also be given anti-thymocyte globulin to prevent rejection of the donated cells. When this conditioning therapy is completed, the stem cells will be infused through the central line. Patients will be given cyclosporine by mouth or by vein from 4 days before until 3 months after the stem cell transplant to help prevent rejection. The average hospital stay for stem cell transplant is 30 days. After discharge, patients will return for follow-up clinic visits weekly or twice weekly for 4 months. These visits will include a symptom check, physical examination, and blood tests. Blood transfusions will be given if needed. Subsequent visits will be scheduled at 4, 6, 12, 18, 24, 30 and 36 months after the transplant or more often if required, and then yearly.
This study will evaluate a new technique for examining the air passages of the lungs called "virtual bronchoscopy." It involves using computed tomography (CT) images of the chest to generate a 3-dimensional model of the walls of the trachea and bronchi (airway passages). This non-invasive method lets doctors see small masses and areas of narrowing in the passages without having to do surgery or pass a tube through them. Patients with diseases of the air passages who are enrolled in an NIH clinical trial may participate in this study, which requires having a CT scan. The patient lies on a table that slowly slides into a hole in a donut-shaped X-ray machine (the scanner). Patients may have to hold their breath several times during the procedure. Some patients may be given an injection of a contrast agent through a catheter (thin tube) placed in an arm vein to improve visibility of abnormalities. Patients may also be asked to breathe oxygen through nasal prongs to allow them to hold their breath longer. The procedure usually takes 15 to 20 minutes.
This protocol will follow patients who participated in NIAID's study Gene Therapy Approach for Chronic Granulomatous Diseases (95-I-0134). No further gene therapy treatments will be given under this protocol. However, because gene therapy is a new technology and involves a permanent change in the genetic code of some cells, patients who have had this treatment require long-term health monitoring. Participants will be asked to provide updated address and telephone information and the names of two contact persons, such as siblings or friends. Patients will be seen about once a year at the NIH Clinical Center to provide an update on their health status and donate a small blood sample (about 2 teaspoons), which will be frozen and stored. If a patient acquires a serious illness, such as cancer, his or her stored blood will be tested; another of blood or tissue sample may also be requested for further study. If a patient develops a medical problem that is thought possibly to be related to gene therapy, the illness will be investigated. The annual follow-up visits will continue indefinitely or until the patient declines to continue participation. Participants may also agree to store some of their blood future research on chronic granulomatous diseases and other medical conditions. Stored samples may be labeled with a code, such as a number, that only the study team can link with the patient. Any identifying information about the patient will be kept confidential as is permitted by law.
In a recent double-blinded, placebo-controlled multi-center international study, subcutaneous injections of interferon-gamma administered three times weekly reduced the frequency of serious infections in patients with chronic granulomatous disease. Patients receiving interferon-gamma had fewer hospital stays, shorter in length, than the placebo group. Children less than 10 years of age benefitted most from treatment and had fewer side effects. Based on these data, the FDA licensed interferon-gamma for prophylaxis in CGD patients. We wish to monitor our patients who participated in the original study for possible long-term side effects. Any new patients referred to us who are either on interferon-gamma or considered to be candidates for interferon-gamma will be considered for this protocol. In addition, our patients who were originally accepted under Genentech's compassionate plea protocol will also be monitored under this new protocol. The patients will be evaluated every six months, with blood work and interim medical histories taken.