Sirolimus for Focal Segmental Glomerulosclerosis

Focal Glomerulosclerosis Clinical Trial

Official title: Sirolimus for Focal Segmental Glomerulosclerosis

Status Completed

Clinical Trial Summary

This study will determine the safety and effectiveness of sirolimus (Rapamune® (Registered Trademark)) in treating focal segmental glomerulosclerosis (FSGS), a disease involving kidney scarring and increased protein in the urine. About one-half of patients with FSGS go on to develop end-stage kidney disease within 6 years, requiring dialysis or kidney transplant. Therapies to reduce urine protein are likely to stop the progression of renal scarring and reduce the chance of developing kidney failure. However, current treatments for FSGS, such as prednisone, cyclophosphamide, and cyclosporine, are not effective in many patients and can cause serious side effects. This study will see if sirolimus, a drug with both anti-scarring and immune suppressing properties, can lower the amount of protein in the urine and slow or stop the kidney disease.

Patients 13 years of age and older with FSGS who have had at least one standard treatment for FSGS may be eligible for this 24-month study. Pregnant and nursing women may not participate. Candidates will be screened with a medical history and physical examination, review of medical records and kidney biopsy, 24-hour urine collection, and blood tests.

Participants will take sirolimus tablets once a day for 1 year. Three 24-hour urine collections will be done before starting treatment. Blood will be drawn to measure drug levels every week for the first month after starting treatment, then every other week for 1 month, and then every 2 months until treatment stops. Patients who do not have a complete response to the drug at low levels will have their dose increased. Patients will be seen at the NIH clinic in Bethesda, Md., for the screening visit and then at 1, 4, 8, 12, and 15 months for blood and urine tests. Additional urine collections and blood tests will be done periodically throughout the 24-month study period by the patient's local physician.

Patients whose urine protein decreases on therapy will be asked to wait 3 months before starting another treatment and will monitored during that time to determine if the response is sustained. Patients whose urine protein levels do not decrease with sirolimus will not be asked to wait 3 months before starting another therapy. Follow-up with the local physician will continue at 18 and 24 months after starting the study.

Patients whose urine protein levels increase with sirolimus treatment will be taken off the study and may seek other treatment at any time.

Clinical Trial Description

Sirolimus is an immunosuppressive agent that was recently approved for use in organ transplantation. We propose to carry out a pilot study whose objectives are to determine the safety and efficacy profile of sirolimus in focal segmental glomerulosclerosis (FSGS). Current therapy for FSGS has limited efficacy. Sirolimus was selected for the following reasons: 1) sirolimus reduces proliferation of mesangial cells and endothelial cells, 2) sirolimus reduces fibrosis in experimental models of liver and kidney disease, 3) sirolimus is a potent immunosuppressive, and other immunosuppressives including glucocorticoids and cyclosporine have shown some efficacy in FSGS, and 4) sirolimus may have a direct anti-proteinuric effect, as suggested by in vitro studies. We will recruit up to 30 patients, including adults and children greater than or equal to 13.0 years of age. The study design is open label, with therapy for one year using doses adjusted to achieve trough levels of 5-15 ng/mL during the first 4 months and if a complete remission is not achieved and sustained, 10-20 ng/mL during the remainder of the study. The primary outcome will be reduction in proteinuria, categorized as complete remission and partial remission, comparing baseline values and 12 month values. The study will recruit patients in two groups: 1) a drug washout group, for patients who can tolerate receiving no immunosuppressive therapy for 4 weeks prior to initiating sirolimus therapy, and 2) a drug overlap group, for patients who cannot tolerate cessation of immunosuppressive therapy due to severe edema or other complications of nephrotic syndrome; these patients will receive prednisone for up to 6 months while taking sirolimus (with a target of prednisone less than 20 mg QOD by month 3) or will receive cyclosporine, tacrolimus, or mycophenolate mofetil for up to 4 weeks while initiating sirolimus therapy. ;

Study Design

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Focal Glomerulosclerosis
• Glomerulosclerosis, Focal Segmental

• NCT number: NCT00040508
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Status: Completed
• Phase: Phase 2
• Start date: June 2002
• Completion date: January 2005