Sirolimus Therapy for Idiopathic and Lupus Membranous Nephropathy
This study will evaluate the safety and effectiveness of a new immunosuppressive drug, sirolimus, in reducing the amount of protein in the urine in patients with membranous nephropathy. This condition involves damage to the walls of tiny blood vessel filters in the kidneys called glomeruli, which allows blood proteins to leak into the urine. Patients have low blood protein levels and high blood cholesterol. Some patients may have leg swelling, impaired kidney function, blood vessel and heart disease, and a risk of emboli (blood clots that travel to the lungs). Drugs currently used to treat membranous nephropathy vary in their effectiveness among patients and can cause severe side effects.
The Food and Drug Administration has approved sirolimus for suppressing the immune system of patients who have had a kidney transplant to reduce the risk of organ rejection. The drug does not have certain side effects that have caused problems for patients treated with other immunosuppressants, such as: prednisone (weight gain, round face, diabetes, weak and fractured bones, and cataracts); cyclophosphamide (fertility problems, bladder injury and bladder cancer, and other cancers); chlorambucil (fertility problems, seizures, acute leukemia, and other cancers); and cyclosporine (kidney toxicity, increased facial hair, and seizures).
Patients 13 years of age or older with idiopathic membranous nephropathy or lupus membranous nephropathy may be eligible for this study. Candidates must have completed at least one month of treatment with a stable dose of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs). They will be screened with a medical history, physical examination, blood tests, skin test for exposure to tuberculosis, and an examination for infection, cancers, and other conditions that can cause membranous nephropathy.
Participants will take sirolimus once a day for 1 year, except for the first day of treatment, when they will take three doses to quickly bring their blood levels of the drug up to a therapeutic level. They will undergo evaluations at the NIH in Bethesda, Maryland, at baseline (before starting treatment) and again at 1- to 4-month intervals during the study. In addition, they will have blood tests every week for the first month and every 2 weeks for the second month; then blood and urine tests once a month for the next 10 months of treatment and then every 4 months for a 12-month period after treatment stops. These tests will evaluate drug side effects and the response to therapy, and will determine if the therapeutic benefits persist long-term when treatment stops.
Patients will also be asked to have optional kidney function tests during the baseline evaluation and at the end of the follow-up period to measure kidney filtration and blood flow rates. Those who participate will be given fluids and other substances by vein to accurately measure kidney function. They will then have blood and urine samples collected about four times over a 1-hour period after drinking fluids to increase urine output.
Patients who experience a substantial increase in proteinuria or substantial decrease in kidney function during the course of treatment will stop taking sirolimus and be taken off the study.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Sirolimus Therapy in Idiopathic and Lupus Membranous Nephropathy|
- The number of patients who are in 1) complete remission or 2) complete or partial remission. [ Time Frame: 12 months after starting sirolimus ] [ Designated as safety issue: No ]
- The number of patients who are in Complete or Partial Remission or Limited Response. [ Time Frame: 12 months after starting sirolimus ] [ Designated as safety issue: No ]
|Study Start Date:||December 2002|
|Study Completion Date:||August 2007|
|Primary Completion Date:||August 2007 (Final data collection date for primary outcome measure)|
This is a phase 2 trial to evaluate the safety and effectiveness of a new immunosuppressive drug, sirolimus, in patients with idiopathic and lupus membranous nephropathy. Patients (age greater than or equal to 13 years) will be invited to participate if they have persistent nephritic range proteinuria despite standard treatment with an angiotensin converting enzyme inhibitor or an angiotensin receptor blocker for at least one month, unless intolerant. These individuals are at risk for renal function deterioration as well as cardiovascular and thrombo-embolic complications of the nephrotic syndrome. Renal function, the degree of proteinuria and side effects will be monitored closely throughout the study. Physiologic measures of glomerular function will be examined at study entry and at the conclusion of the trial.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Howard A Austin, M.D.||National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)|