NIH Clinical Research Studies

Protocol Number: 00-DK-0042

Active Accrual, Protocols Recruiting New Patients

Title:
Pirfenidone in Focal Segmental Glomerulosclerosis Phase II Study
Number:
00-DK-0042
Summary:
This study will examine the effectiveness of the drug pirfenidone in treating focal segmental glomerulosclerosis (FSGS). Patients with this disease have kidney fibrosis (scarring) and proteinuria (excessive excretion of protein in the urine). About half of patients with FSGS eventually require kidney dialysis or transplant. Steroids, which are currently used to treat the disease, are effective in only a minority of patients. Other drugs, such as cyclosporin and cyclophosphamide, improve proteinuria in a very small percentage of patients and have serious side effects.

Patients with FSGS who wish to participate in this study will undergo pre-study evaluation with blood and urine tests. Patients must be on a stable dose of an ACE inhibitor (a drug that lowers blood pressure and reduces proteinuria) for at list 6 months before starting pirfenidone therapy. (Patients who are not already taking an ACE inhibitor will be started on the drug; those who cannot tolerate ACE inhibitors will be given a different drug.) Patients with elevated cholesterol will take a cholesterol-lowering drug. A diet containing approximately 1 gram of protein per kilogram of body weight per day will be recommended.

Patients will take pirfenidone by mouth 3 times a day for 12 months. Blood and urine will be tested once a month, either at NIH or by the patient's local kidney specialist. They will collect two 24-hour urine samples at the beginning of the treatment period, at 2-month intervals throughout the study, and at a 6-month follow-up. Patients will also be asked to give three to five tubes of blood and urine samples for analysis during the study.

In animal studies, pirfenidone improved kidney function and proteinuria and reduced kidney scarring in rats with a disease similar to FSGS. In human studies, pirfenidone improved breathing and survival in patients with lung fibrosis.

Sponsoring Institute:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): None

Eligibility Criteria:
INCLUSION CRITERIA:

Adults greater than or equal to 18 years of age.

Patients will provide informed consent.

Biopsy proven FSGS.

Glomerular filtration rate of at least 25 and no more than 80 ml/minute as assessed by the 4 variable MDRD equation.

At least 6 months of renal function data must be available prior to the patient's receiving pirfenidone, and renal function must show a rate of decline of greater than or equal to 0.4 ml/min/month during this baseline period.

Patients must have received no glucocorticoids, cyclophosphamide, mycophenolate or other immunosuppressive drugs for at least 2 months prior to the study period.

Patients must have received no cyclosporin for at least 6 months prior to the study period.

Patients must have been taking an angiotensin converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at a stable dose for at least 6 months, unless intolerant of both classes of medication.

Patients who are HIV seropositive will receive standard care for HIV disease (patients receiving immune-modulating therapy will be excluded).

Women with child-bearing potential must maintain an effective birth control regimen (oral contraceptive, intrauterine device, barrier plus spermicide).

Men will be advised that although Ames testing has been negative for any evidence of mutagenicity, they should consider use of contraceptives during the study period as well.

EXCLUSION CRITERIA:

Inability to give informed consent of cooperate with study.

Known intolerance to pirfenidone.

Evidence of FSGS associated with an additional primary or secondary glomerular disease (e.g. diabetes, membranous nephropathy, IgA nephropathy).

Recent (within 6 months) history of myocardial infarction.

History of peptic ulcer within 6 months.

History of cerebrovascular disease manifested by transient ischemic attack or cerebrovascular accident within 6 months.

Pregnancy, breast feeding or inadequate birth control.

History of photosensitivity dermatitis.

Concurrent drug treatment with gemfibrozil, cyclosporin or erythromycin, potassium-sparing diuretics and other drugs which may potentiate hyperkalemia, or concurrent immunosuppresive medications.

Requirement for NSAID therapy.

Requirement for interleukin-2 therapy or other immune-modulating medication.

Existence of any other condition which would complicate the implementation or interpretation of the study.

Renal transplant.

Evidence of significant hepatic disease, as indicated by serum transaminases greater than 3 times upper limit of normal, protime greater than 2 seconds prolonged.

Special Instructions: Currently Not Provided
Keywords:
Fibrosis
Nephrotic Syndrome
Proteinuria
Renal Failure
TGF-Beta
Recruitment Keywords:
Focal Segmental Glomerulosclerosis
FSGS
Conditions:
Fibrosis
Focal Glomerulosclerosis
Kidney Failure
Nephrotic Syndrome
Proteinuria
Investigational Drug(s):
Pirfenidone
Investigational Device(s):
None

Contacts:
Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citations:
Antiproteinuric therapy while preventing the abnormal protein traffic in proximal tubule abrogates protein- and complement-dependent interstitial inflammation in experimental renal disease

Renal TGF-beta in HIV-associated kidney diseases

Transforming growth factor beta in tissue fibrosis

Active Accrual, Protocols Recruiting New Patients

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