Rituximab Plus Cyclosporine in Idiopathic Membranous Nephropathy
Status:
Recruiting
Trial end date:
2023-01-01
Target enrollment:
Participant gender:
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.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)