8 Clinical Trials for Various Conditions
The aim of this project is to develop a disease specific patient reported outcome measure (PROM) for patients with AAV (the AAV-PRO). Investigators are developing and validating a questionnaire to assess quality of life in patients with ANCA-associated vasculitis (AAV). Patients with AAV have inflammation in the small blood vessels leading to involvement of a range of organs and can suffer from ongoing disease activity or treatment side effects. Quality of life can be measured by patient reported outcome measures (PROMs).
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 is a randomized controlled trial in patients with a diagnosis of granulomatosis with polyangiitis (GPA; Wegener's)that are in remission to evaluate the effects of using low-dose glucocorticoids ( 5 mg/day of prednisone) as compared to stopping glucocorticoid treatment entirely (0 mg/day of prednisone)on rates of disease relapse/disease flares. This study is a novel approach to conducting a randomized clinical trial in the community setting. This study is being conducted in parallel with a similar study at established vasculitis institutions. This study will have a patient centric approach to research in that subjects will be recruited online and through social media and vasculitis support networks. Participants will be consented online and will receive care through their regular treating physician so no travel or additional doctor visits are required. Study participants will consent to the study and complete online questionnaires about their prednisone dose and about how they are feeling.
This study is a multi-center randomized controlled trial to evaluate the effects of using low-dose prednisone as compared to stopping prednisone treatment entirely. Participants will be randomized 1:1 to taper their prednisone dose down to 5 mg/day or to 0 mg/day for the duration of the study (approximately six months) or until a study endpoint.
The purpose of this study is to evaluate the efficacy and safety of belimumab, in combination with azathioprine, for the maintenance of remission following a standard induction regimen in patients with Wegener's granulomatosis or microscopic polyangiitis. The random assignment in this study is "1 to 1" which means that participants have an equal chance of receiving belimumab or placebo.
Granulomatosis with polyangiitis (Wegener's) (GPA) and microscopic polyangiitis (MPA) are two rare immune system disorders that cause the inflammation of blood vessels, or vasculitis. In order to properly treat these diseases, it is critical that the level of disease activity can be determined over the course of the disease. The purpose of this study is to determine new biological markers, or biomarkers, that may be used to assess the severity of disease in people with GPA or MPA.
The purpose of this study is to identify genes that increase the risk of developing vasculitis, a group of severe diseases that feature inflammation of blood vessels. Results of these studies will provide vasculitis researchers with insight into the causes of these diseases and generate new ideas for diagnostic tests and therapies, and will be of great interest to the larger communities of researchers investigating vasculitis and other autoimmune, inflammatory, and vascular diseases.