Membranous Glomerulonephritis Clinical Trial
Official title:
Sirolimus Therapy in 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.
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 nephrotic 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. ;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT00977977 -
Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
|
Phase 2 |