Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
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|ClinicalTrials.gov Identifier: NCT00977977|
Recruitment Status : Recruiting
First Posted : September 16, 2009
Last Update Posted : August 6, 2020
- 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.
- To determine the safety and effectiveness of combining rituximab and cyclosporine to treat membranous nephropathy.
- 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.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Nephrotic Syndrome Proteinuria Autoimmune Disease Glomerular Disease Membranous Glomerulonephritis||Drug: Rituximab Infusion Drug: Oral Cyclosporine||Phase 2|
This is a pilot intervention study to evaluate preliminary evidence of the safety and effectiveness of a novel combination immunosuppressive regimen, Rituximab plus cyclosporine, in the treatment of idiopathic membranous nephropathy. Membranous nephropathy is a condition that affects the kidney and involves damage to the walls of tiny blood vessels filters in the kidneys called glomeruli. This damage allows blood proteins to leak into the urine (proteinuria). As a result, patients have low protein levels in the blood, high blood cholesterol levels and often develop leg swelling. This combination of symptoms and signs is called the nephrotic syndrome. Some patients with membranous nephropathy develop impaired kidney function and a proportion of these patients may develop kidney failure. The immunosuppressive drugs that are most often used to treat membranous nephropathy include cyclophosphamide plus steroids or cyclosporine. These vary in their effectiveness among patients and there are side effects with each treatment. Rituximab alone has been used experimentally to treat membranous nephropathy in small clinical trials. It has been associated with decreased proteinuria of variable degrees in some patients.
The purpose of this pilot study is to evaluate whether the combination of Rituximab plus cyclosporine, two drugs with different effects on the immune system, results in a greater number of remissions of the nephrotic syndrome and more sustained remissions than is expected with cyclosporine alone. 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.
Patients age 18 years and older with idiopathic membranous nephropathy will be eligible to participate in this study. Pregnant and nursing women may not participate. Candidates must have persistent nephrotic syndrome despite a 6 month observation period and treatment with angiotensin converting enzyme inhibitors or angiotensin receptor blocker. Candidates will be screened with a medical history, physical examination, blood and urine tests, review of the medical records and kidney biopsy results.
Participants will come to NIH in Bethesda, Maryland for evaluation and to receive intravenous infusions of Rituximab. Two doses of Rituximab will be given (2 weeks apart). Participants will also take cyclosporine pills twice a day. After 6 months, the dose of cyclosporine will be tapered over several weeks and then discontinued. Patients will be re-treated with a second course of Rituximab (two infusions given two weeks apart) after a minimum of 6 months has passed since completing the first course of Rituximab. The exact timing of the second course of Rituximab will depend on the results of blood tests. All patients will be followed for a minimum of 24 months from the time that therapy is initiated.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy|
|Actual Study Start Date :||December 2, 2010|
|Estimated Primary Completion Date :||January 1, 2021|
|Estimated Study Completion Date :||January 1, 2021|
Experimental: Combination of Rituximab plus 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.
Drug: Rituximab Infusion
Drug Rituximab Infusion 2 infusions (each 1000 mg) separated by 2 weeks; repeated after 6 months
Drug: Oral Cyclosporine
Daily therapy for 6 months (3-5 mg /kg), then tapered and discontinued
- Safety [ Time Frame: 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) [ Time Frame: 6 months ]Proteinuria; complete remission (CR) defined as less than 300 mg/24proteinuria and partial remission (PR) <3.5 grams /day and >=50%reduction of proteinuria
- Percentage of complete and partial remissions (CR and PR) [ Time Frame: 12 months ]Proteinuria; complete remission (CR) defined as less than 300 mg/24proteinuria and partial remission (PR) <3.5 grams /day and >=50%reduction of proteinuria
- Percentage of complete and partial remissions (CR and PR) [ Time Frame: 18 months ]Proteinuria; complete remission (CR) defined as less than 300 mg/24proteinuria and partial remission (PR) <3.5 grams /day and >=50%reduction of proteinuria
- Percentage of complete and partial remissions (CR and PR) [ Time Frame: 24 months ]
- Time to remission Baseline to 24 months [ Time Frame: Baseline to 24 months ]
- Change in proteinuria from baseline to 12 months [ Time Frame: Baseline to 12 months ]
- Time to relapse (in those who achieved a remission) [ Time Frame: Baseline to 24 months ]
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00977977
|Contact: Lilian V Howard, C.R.N.P.||(301) email@example.com|
|Contact: Meryl A Waldman, M.D.||(301) firstname.lastname@example.org|
|United States, Maryland|
|National Naval Medical Center||Recruiting|
|Bethesda, Maryland, United States, 20889|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR) 800-411-1222 ext TTY8664111010 email@example.com|
|Principal Investigator:||Meryl A Waldman, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|