View clinical trials related to Wegener's Granulomatosis.
Filter by:Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis is the most common type of small blood vessel inflammation in adults. ANCA-associated vasculitis includes Wegener's granulomatosis (WG) and microscopic polyangiitis (MPA). Rituximab is a man-made antibody used to treat certain types of cancer. The purpose of this study is to determine the effectiveness of rituximab in treating patients with WG and MPA. Study hypothesis: Rituximab is not inferior to conventional therapy in its ability to induce disease remission by Month 6.
This study will examine the use of rituximab in patients with Wegener's granulomatosis (WG) who have experienced a relapse of the disease through standard therapies. Rituximab is an antibody directed against the human protein called CD20, found on the surface of normal and abnormal B lymphocytes. Rituximab decreases the number of B lymphocytes. This study will examine the safety of rituximab in WG and rituximab's ability to reduce the level of circulating antineutrophil cytoplasmic antibodies (ANCA), which are antibodies that react to substances found in white blood cells. ANCA have been found to be strongly associated with WG. The study will also explore whether rituximab can reduce the occurrence of disease relapse. WG is a disease marked by inflammation of blood vessels. It can involve many different parts of the body, including the sinuses, lungs, kidneys, brain, nerves, eyes, intestinal tract, skin, joint, heart, and others. Before the use of cytotoxic drug therapy, WG was almost always fatal if untreated, with a mortality rate of 93% within 2 years. Patients 18 to 75 years of age who have a history of at least one relapse of the disease despite standard treatments, who have had active WG within the previous 12 months and are in remission, who are receiving either methotrexate or azathioprine for remission maintenance, and who have circulating ANCA, may be eligible for this study. A minimum of 22 visits to the clinic will be required to complete the entire study. Patients will undergo a comprehensive medical evaluation, with laboratory studies and x-rays. There may also be consultations and possible biopsies of affected organs only if medically indicated for diagnosis and treatment of the disease. In the 4-week period that patients will receive rituximab infusions, the methotrexate or azathioprine will be continued at the same dosage unless there are side effects that requite the medication to be temporarily stopped or the dosage reduced. Patients will receive four doses of rituximab, at 375 mg per meter squared of body surface area, once a week. It will be infused into a vein, through an intravenous catheter. For the first dose, patients will be admitted as inpatients for at least 24 hours, for monitoring during the infusion and for any reactions associated with it. The second, third, and fourth rituximab infusions may be given either on an inpatient or outpatient basis to be decided on how the patient tolerates the first infusion. Following the four infusions, there will be blood tests to monitor the safety of the medication and the status of the disease, to be done at home every week for 4 weeks. Results will be sent to the researchers by fax. Patients will be asked to return to the clinic 1 month after the fourth infusion and every 1 to 3 months afterward. If there are no side effects or a relapse of the disease, the methotrexate or azathioprine will be continued for 2 years past remission. If by then the disease then remains in remission, the dose of either medication will be gradually decreased and eventually stopped. The usual schedule is to reduce methotrexate by 2.5 mg per month and to reduce azathioprine by 25 mg per month. If at that point there are no signs of active disease, the patients' illness will be considered to be in continued remission and no further treatment will be necessary. If relapse does occur, treatment would be different than previously. In most cases, treatment would involve prednisone and cyclophosphamide or methotrexate If the ANCA finding is negative after rituximab treatment and again becomes positive, and there is evidence of a return of B lymphocytes, patients may receive a second course of four rituximab infusions.
This study will examine the safety and effectiveness of daclizumab (also called Zenapax or anti-CD25) in patients with Wegener's granulomatosis, a type of vasculitis (blood vessel inflammation). Wegener's granulomatosis can affect many parts of the body, including the brain, nerves, eyes, sinuses, lungs, kidneys, intestinal tract, skin, joints, heart, and other sites. Standard treatment is a combination of prednisone and a cytotoxic agent (a drug that interferes with cell growth), usually cyclophosphamide or methotrexate. However, many patients treated with this regimen have a disease relapse, and others cannot take these drugs because of severe side effects. This study will focus on the effectiveness of daclizumab in preventing disease relapse. The Food and Drug Administration approved daclizumab in 1997 for preventing kidney transplant rejection, and the drug has also been studied in people with an eye infection called uveitis. The drug works by binding to a protein on T lymphocytes (white blood cells of the immune system) called CD25. This prevents another protein, called interleukin-2, from binding to this site, thereby preventing a series of events that normally results in inflammation. Patients between 10 and 75 years of age with Wegener's granulomatosis may be eligible for this study. Participants will have a medical history review and physical examination, including laboratory studies. If medically indicated, x-rays, consultations and biopsies (surgical removal of a small tissue sample) of affected organs will also be conducted. All patients will begin treatment with prednisone and cyclophosphamide daily. Those who improve on this regimen will reduce the prednisone gradually and continue with cyclophosphamide until their disease is in remission. While taking cyclophosphamide, patients must have blood and urine tests done every 1 to 2 weeks. Those who achieve disease remission will stop cyclophosphamide and start taking methotrexate once a week, usually by mouth but possibly by injection into the muscle or skin. Blood and urine tests will be conducted once a week for 4 weeks while the dosage is being adjusted and then once a month for the duration of treatment. Patients on methotrexate whose prednisone dose is reduced to 10 to 30 mg every other day will be randomly assigned either to receive or not receive daclizumab in addition to the methotrexate. Daclizumab is given intravenously (through a plastic tube inserted into a vein) the day after the randomization, then again in 2 weeks, 4 weeks, and once a month for 18 months. All patients will continue to taper their prednisone dose until it is stopped. Methotrexate will continue for 2 years. Patients whose disease remains in remission at this time will decrease the methotrexate dose. If there is no active disease when both prednisone and methotrexate have been stopped, no further treatment will be given. If disease recurs at a later time, treatment will be reinstituted. The treatment will be determined by the severity of disease, other medical conditions, and history of side effects. Patients not randomized to daclizumab who relapse while still taking methotrexate may be offered re-treatment with daclizumab. Patients will be evaluated in the outpatient clinic every 4 to 8 weeks until randomization. Patients not taking daclizumab will be followed every 4 to 12 weeks; those taking the drug will be seen every 2 weeks for the first month, every month after that during the 18-month treatment period, and every 4 to 12 weeks until all medications stop. Follow-up evaluations include a physical examination, blood draws and, if medically indicated, X-rays. The total study duration is 60 to 70 months.
This study will determine if the drug etanercept, also called Enbrel, is effective in producing and maintaining remission (reduction of disease symptoms) of Wegener's granulomatosis (WG). Etanercept blocks the action of tumor necrosis factor-alpha, a substance that may be involved in inflammatory conditions such as WG. Eight clinical centers around the United States will enroll 181 people who have WG. Patients will have an equal chance to receive either etanercept or placebo (inactive treatment). We will treat patients with standard medications for WG in addition to either etanercept or placebo. We will treat all patients with tapering doses of corticosteroids. After the patients' disease is controlled (in remission), we will reduce the dosages of the standard medications to lower the risk of side effects associated with these drugs. During the study, we will collect and save blood and tissues samples from patients and use the samples to address other medical questions, such as the cause of WG and factors that lead to disease progression.
This study will compare the safety and effectiveness of two drugs-methotrexate and mycophenolate mofetil (MPM)-in preventing disease recurrence in patients with Wegener's granulomatosis and related inflammatory blood vessel disorders. The standard treatment for these conditions is combination drug therapy with prednisone plus cyclophosphamide. However, although most patients improve on this therapy and achieve disease remission, many experience a relapse (return of the disease) some time after therapy is stopped. Also, these drugs can produce serious side effects during treatment. This study will test a new treatment regimen to try to maintain disease remission in these patients with minimal side effects. Patients with Wegener's granulomatosis or other related blood vessel disorders between 10 and 80 years old will be considered for this study. All participants will start therapy with daily doses of prednisone and cyclophosphamide. Prednisone will be reduced gradually and then stopped after symptoms improve significantly. Cyclophosphamide will continue until the disease is in remission. Patients in remission will then be randomly assigned to continue treatment with either MPM or methotrexate. MPM is taken twice a day by mouth. Methotrexate is taken once a week, usually by mouth, but in some cases, by injection into a muscle or under the skin. Patients who do well and have no side effects will continue treatment for 2 years. Then, the drug will gradually be reduced (usually at monthly intervals) and finally stopped. No further treatment will be given unless a relapse occurs. At that time, the type of treatment will depend on various medical factors, including the severity of the recurrence and the patient's history of drug side effects. Physical examinations and various tests, including blood and urine analyses, and X-rays, will be done periodically to evaluate the response to treatment and monitor drug side effects. The total duration of the study-from the screening evaluation through a 2-year follow up after all medications have been stopped-is about 5 to 6 years.
This study will examine the use of etanercept (also called Enbrel or TNFR:Fc) in patients with Wegener's granulomatosis, a type of vasculitis (blood vessel inflammation). Wegener's granulomatosis may affect many parts of the body, including the brain, nerves, eyes, sinuses, lungs, kidneys, intestinal tract, skin, joints, heart, and other sites. Generally, the greater the disease involvement, the more life-threatening it is. Standard treatment is a combination of prednisone and a cytotoxic agent-usually cyclophosphamide or methotrexate. However, many patients treated with this regimen have a disease relapse, and others cannot take these drugs because of severe side effects. This study will evaluate etanercept's safety and effectiveness, and particularly its value in reducing the need for prednisone and preventing disease relapse. The Food and Drug Administration has approved etanercept for treating rheumatoid arthritis, another inflammatory disease. The drug works by blocking the activity of TNF-a protein made by white blood cells that is involved in the inflammatory process. Since prednisone also affects inflammatory proteins and lowers TNF production, the use of etanercept may reduce the need for prednisone in patients with Wegener's granulomatosis, and thus the risk of its side effects. Patients between 10 and 70 years of age with Wegener's granulomatosis who have never taken prednisone, methotrexate or cyclophosphamide, or have taken these drugs for less than 3 weeks may be eligible for this study. Participants will have a medical history review and physical examination, including laboratory studies. If medically indicated, X-rays, consultations and biopsies (surgical removal of a small tissue sample) of affected organs will also be done. All patients will begin treatment with prednisone, methotrexate and etanercept. Those who improve on this regimen will stop prednisone gradually over 3 months. Those who achieve disease remission at the end of another 3 months will be randomly assigned to either continue taking etanercept and methotrexate for another 12 months or to stop etanercept and continue only methotrexate for the next 12 months (after which methotrexate will gradually be stopped). Patients who are not in remission by the 6-month point will continue taking etanercept until they go into remission, when they will be assigned to stop or not stop etanercept, as described above. Patients who do not achieve remission within 12 months of beginning treatment will be taken off the study. Patients who have a disease relapse while on the study will likely be switched to treatment with prednisone and either methotrexate or cyclophosphamide. Patients randomized to stop etanercept and who have a relapse within a year of stopping the drug may be offered re-treatment on this protocol, but with continuing etanercept for a full year after remission. Patients will be evaluated in the outpatient clinic every 2 to 4 weeks for the first 4 months and every 1 to 3 months after that. Patients whose disease is in remission and who stop all medications will be followed every 3 to 6 months for 2 years. Follow-up evaluations include a physical examination, blood draws and, if medically indicated, X-rays. The total study duration is 60 to 70 months.
This study will examine the safety and effectiveness of the drug mycophenolate mofetil (MPM) in treating Wegener's granulomatosis and related inflammatory vessel diseases. Blood vessel inflammation in these patients may involve different parts of the body, including the brain, nerves, eyes, sinuses, lungs, kidneys, intestinal tract, skin, joints, heart, and other sites. The more severe the involvement, the more likely the disease will be life-threatening. Standard treatment consists of combination drug therapy with prednisone and a cytotoxic agent-usually cyclophosphamide or methotrexate. However, some patients in whom this treatment is initially successful have a disease relapse; other patients cannot take the medications because of other health problems or because of severe side effects of the drugs. MPM is approved by the Food and Drug Administration to prevent kidney transplant rejection. It is chemically similar to another cytotoxic drug called azathioprine, which has been beneficial in maintaining remission in patients with Wegener's granulomatosis who have been treated successfully with cyclophosphamide. Because MPM is more effective than azathioprine in preventing organ rejection, it may also prove beneficial as a second-line treatment for Wegener's granulomatosis. Patients with Wegener's granulomatosis or related inflammatory vessel diseases who have had a relapse following treatment with cyclophosphamide and methotrexate or who cannot take one or both of these drugs may be eligible for this study. Only patients who have been treated at NIH in the methotrexate protocol or the cyclophosphamide switching to methotrexate protocol, or who have received the exact same treatment from their own physician may participate. Participants will have a complete medical evaluation including laboratory studies. Consultations, X-rays and biopsies of affected organs may also be done if indicated for diagnosis or treatment. Patients with active disease will be given MPM and prednisone, both in tablet form. Patients with inactive disease will receive only prednisone if they are already taking it. In both cases, the prednisone will be reduced gradually and discontinued if the disease improves significantly. MPM therapy will continue for at least 2 years. If after 2 years the disease remains in remission, the MPM dose will be gradually reduced and then stopped. If active disease recurs while on MPM therapy, the treatment plan will likely be changed. The new regimen will be determined by the severity of disease, other medical conditions, and history of side effects to previous medications. Patients will be followed at the NIH clinic every month for the first 3 months on MPM and then every 3 months for another 18 months. Those whose disease has remained in remission and have stopped all medications will then be followed every 6 months for 4 visits. The follow-up visits will include a physical examination, blood draws, and, if needed, X-rays. Visits may be scheduled more frequently if medically indicated.
The purpose of this study is to assess the safety, tolerance, and immunologic effects of interleukin-10 (IL-10), in patients with Wegener's granulomatosis. A secondary objective is to determine if IL-10 demonstrates sufficient anti-inflammatory activity in the treatment of Wegener's granulomatosis to warrant further study in a larger trial. In this study, IL-10 will be given either alone or in combination with standard therapeutic agents, usually consisting of cyclophosphamide, methotrexate, and/or prednisone. Patients will be eligible to receive IL-10 when there is evidence of active disease. IL-10 will be administered by subcutaneous injection at a dose of 4 µ (Micro)g/kg/day for 28 days.
Asthma is a chronic inflammatory disease. We propose to study inflammatory changes in the lungs of subjects with atopic asthma of different severity in vivo using positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose (FDG). It has been shown that the uptake of FDG as detected by PET scanning correlates with inflammation in animal models as well as in human disease processes such as sarcoidosis, tuberculosis and abscess formation. In addition, it has been shown that the inflammation associated with allergen challenge in patients with atopic asthma can be visualized using PET scanning with FDG. We hypothesize that the degree of FDG-uptake as a measure of inflammation correlates with the severity of asthma as determined by pulmonary function tests and clinical signs and symptoms. In addition, information about the spatial distribution of the inflammatory changes will be obtained. To compare the characteristics of the inflammation in asthma with non-asthmatic inflammation of the lung, the images obtained in asthmatic subjects will be compared with images from subjects who have inflammatory changes of the lung caused by Wegener's granulomatosis. Subjects with atopic asthma and non-atopic control subjects will be selected from the community and, if eligible for the study, undergo skin testing against common allergens and pulmonary function testing. Subjects with Wegener's granulomatosis will be selected from a large group of subjects followed with this disease at NIAID. PET scanning with FDG will be used to measure inflammation in the PET scanning facility at the Clinical Center of the NIH and the results of the scanning will be correlated with the severity of the disease. We expect that for the first time this methodology will permit an objective measure of the basic pathogenic process, the allergic inflammation, in patients with atopic asthma. Using this methodology it will be possible to study the efficacy of currently available therapies for allergic inflammation. In addition, this methodology will provide an extremely useful tool for the development of new therapeutic approaches to the treatment of asthma.
This study will collect fluid and tissue samples from the bronchi (air passages to the lungs) of patients with Wegener's granulomatosis for laboratory examination. Wegener's granulomatosis is a type of vasculitis (blood vessel inflammation) that can affect many parts of the body, including the brain, nerves, eyes, skin, sinuses, kidneys, intestinal tract, joints, heart, lungs and other sites. About 85 percent of patients have lung involvement. The lining of the bronchi (bronchial mucosa) is composed of cells that produce mucus, inflammatory cells, and inflammatory mediators (chemicals produced in response to inflammation). Analysis of these various substances may provide insight into what causes different types of lung problems in Wegener's granulomatosis. Patients between 18 and 75 years of age with Wegener's granulomatosis who require bronchoscopy to evaluate the cause of their lung problem may be eligible for this study. Participants will undergo a bronchoscopy in the hospital intensive care unit (ICU). For this procedure, the mouth and throat are numbed with lidocaine jelly and spray. If needed, a sedative is given for comfort. A small plastic tube (intravenous catheter) is placed in a vein to give medications. A pencil-thin tube is then placed through the nose or mouth into the lung airways to examine the airways carefully. At the time of the bronchoscopy, patients in this study will undergo the following additional procedures: - Bronchoalveolar lavage - Saline (salt water) is injected through the bronchoscope into the air passage, acting as a rinse. A sample of the fluid is then withdrawn and examined for infection, inflammatory cells and inflammatory chemicals. (This may be done as part of the standard medical care procedure.) - Bronchial lavage - This procedure is similar to bronchoalveolar lavage, but less fluid is used to rinse larger airways. - Bronchial mucosal biopsies - A small wire is inserted through the bronchoscope next to the bronchial lining. Forceps at the end of the wire pinch off a small piece of tissue for withdrawal and examination. The patient's heart rhythm and rate and oxygen levels are monitored during the procedure. When the procedures are finished, the patient is monitored in the ICU until the numbing effect of the anesthetic has worn off and then moves to a regular hospital bed for overnight. Patients whose test results show an isolated infection or isolated Wegener's lung tissue involvement and who are being treated or are eligible for treatment under another NIH protocol will be followed by X-ray for improvement of their infection or other lung involvement with treatment. Patients whose infection or lung tissue involvement improves may be asked to undergo a second bronchoscopy as described above, but for research purposes only.