Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
- Conditions
- Nephrotic SyndromeProteinuriaAutoimmune DiseaseGlomerular DiseaseMembranous Glomerulonephritis
- Interventions
- Registration Number
- NCT00977977
- Brief Summary
Background:
* Membranous nephropathy is associated with damage to the walls of the glomeruli, the small blood vessels in the kidneys that filter waste products from the blood. This damage causes leakage of blood proteins into the urine and is associated with low blood protein levels, high blood cholesterol values, and swelling of the legs. These problems can decrease or go away without treatment in about 25 percent of patients, but if they persist, some patients may experience impaired (or loss of) kidney function, blood vessel and heart disease, and a risk of forming blood clots in veins.
* Kidney biopsies that show that antibodies have been deposited along the glomeruli suggest that specialized cells of the immune system, called B and T cells, are causing damage to the kidneys through their increased activity. To suppress the action of B and T cells and to decrease the harmful deposits in the kidneys, drug treatments are required.
* Patients with membranous nephropathy are often treated with immunosuppressive drugs such as cyclosporine or cytoxan plus steroids that attempt to reduce or suppress the activity of the immune system, decrease antibody production, and reduce antibody deposits in the kidney. However, not everyone responds to these medications and the kidney disease can return in some patients when the drugs are stopped. Also, there are side effects associated with long term usage of these medications. Rituximab, a different immunosuppressant, has also been used for this purpose. Although cyclosporine and Rituximab have been used separately, they have not been tried in combination as a possible treatment for membranous nephropathy.
Objectives:
- To determine the safety and effectiveness of combining rituximab and cyclosporine to treat membranous nephropathy.
Eligibility:
- Individuals 18 years of age and older who have been diagnosed with membranous nephropathy based on a kidney biopsy done within the preceding 24 months, and who have had excess levels of protein in the urine for at least 6 months based on urine and blood tests.
Design:
* Potential participants will be screened with an initial clinic evaluation and full medical history.
* Before the treatment, there will be a run-in period that will last up to 2 months. During this time, participants will be placed on a blood pressure lowering medication and will not take any other immunosuppressant medications.
* Participants will visit the NIH clinical center for a baseline evaluation, four intravenous infusions of rituximab, and also at 1- to 6-month intervals throughout the study.
* Active treatment period will involve a 6-month course of cyclosporine and a total of four doses of rituximab. Participants will take cyclosporine tablets twice daily, and have two infusions of rituximab given 2 weeks apart, After 6 months, the cyclosporine dose will slowly be decreased over several weeks and then completely discontinued. Participants will then receive another course (two doses 2 weeks apart) of rituximab, depending on results of blood work.
* Participants will have frequent blood and urine tests performed to monitor the results of treatment and reduce the chance of side effects.
- Detailed Description
Study Description:
Subjects with idiopathic membranous nephropathy will be treated with a combination of rituximab and cyclosporine. The study hypothesis of combining Rituximab and cyclosporine provides more effective immunosuppression than either agent alone by targeting both arms of the immune system which are believed to be involved in the pathogenesis of MN. The combination of Rituximab and cyclosporine may achieve greater reductions in proteinuria, increase the number of remissions (especially complete) of the nephrotic syndrome, decrease the number of relapses and perhaps reset the immune system, thereby obviating the need for long term immunosuppression. The prolonged effects of Rituximab on the immune system may allow for withdrawal of cyclosporine. Although each of these medications has been used separately in membranous nephropathy, the potential benefits and risks of this combination have not yet been formally explored.
Objectives:
Primary objective:
To determine the safety and effectiveness of combining rituximab and cyclosporine to treat membranous nephropathy by evaluating the acceptable safety profile and efficacy to reduce proteinuria.
Secondary objective:
To evaluate the efficacy to maintain durable remission.
Endpoints:
Primary endpoint:
Incidence of adverse events (AEs) will be assessed using the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE).
Number of subjects who achieve complete remission (CR), partial remission (PR) at 6, 12, and 18 months.
Secondary endpoint:
1. Time to remission
2. Time to relapse (in those who achieved a remission)
3. Change in proteinuria from baseline to 12 months
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 30
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Combination of Rituximab plus cyclosporine Rituximab Infusion 2 infusions (each 1000 mg) separated by 2 weeks; repeated after 6 months. Daily therapy for 6 months (3-5 mg/kg), then tapered and discontinued. Combination of Rituximab plus cyclosporine Oral Cyclosporine 2 infusions (each 1000 mg) separated by 2 weeks; repeated after 6 months. Daily therapy for 6 months (3-5 mg/kg), then tapered and discontinued.
- Primary Outcome Measures
Name Time Method Safety 24 months Safety 24 months We will assess using the National Cancer Institute common Terminology Criteria for Adverse Events (CTCAE)
Percentage of complete and partial remissions (CR and PR) 12 months Proteinuria; complete remission (CR) defined as less than 300 mg/24 proteinuria and partial remission (PR) \<3.5 grams/day and \>=50%reduction of proteinuria
- Secondary Outcome Measures
Name Time Method Change in proteinuria from baseline to 12 months Baseline to 12 months Time to remission Baseline to 24 months Baseline to 24 months Time to relapse (in those who achieved a remission) Baseline to 24 months
Trial Locations
- Locations (2)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
National Naval Medical Center
🇺🇸Bethesda, Maryland, United States