Clinical trial NCT00063583: Pirfenidone: A New Drug to Treat Kidney Disease in Patients With Diabetes
Official title: Pirfenidone: A Novel Anti-Scarring Therapy for Diabetic Nephropathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Diabetes Mellitus
Diabetic Nephropathy
Keywords: Kidney disease
Lead sponsor: Sharma, Kumar, M.D.
Sponsor class: INDIV
Collaborators: name: National Institutes of Health (NIH)
name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2003-07-02
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether a new investigational drug, pirfenidone, will be an effective therapy for diabetic patients with kidney dysfunction. Our hypothesis is that administration of pirfenidone to type 1 and type 2 diabetic patients with advanced kidney disease will lead to preservation of kidney function.

Detailed description: Diabetic kidney disease is the leading cause of new cases of kidney failure in the United States. In the kidneys of diabetic patients, there is accumulation of protein that leads to the formation of scar tissue and poor kidney function. Because of this many patients eventually require dialysis or kidney transplantation. A new investigational drug, pirfenidone, has been shown to be beneficial in a number of diseases in which scar formation leads to disease progression. It is our goal to examine whether pirfenidone is effective at stabilizing or reducing progressive diabetic kidney dysfunction.

Eligibility criteria: Inclusion

* Type 1 or type 2 diabetes
* Males and females greater than or equal to 18 years.
* Abnormal kidney function determined by glomerular filtration rate
* History of proteinuria
* Blood pressure controlled to \<140/90 on anti-hypertensive medication

Exclusion

* Cancer, liver disease, hepatitis, HIV+
* History of heart attack, unstable angina, stroke or peptic ulcer in the past 6 months
* Pregnant or planning to become pregnant during the study period
* Other known kidney disease besides diabetic nephropathy
* Expect to begin dialysis or receive a kidney transplant within 1 year of study enrollment

Primary outcomes:
measure: The primary endpoint will be the change in renal function from baseline to the end of the study period (12 months).
timeFrame: 12 months
Secondary outcomes:
measure: % change in urine albumin excretion from baseline to end of study period.
timeFrame: 12 months
measure: % change in levels of TGF-b1 in urine, plasma and serum from baseline to end of study period.
timeFrame: 12 months
measure: • Determine the relationship between % change in TGF-b1 levels and the change in GFR
timeFrame: 12 months
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
state: Maryland
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Philadelphia
country: United States
facility: The Center for Diabetic Kidney Disease at Thomas Jefferson University
state: Pennsylvania
Study officials:
affiliation: UCSD
name: Kumar Sharma, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sharma K, Ziyadeh FN, Alzahabi B, McGowan TA, Kapoor S, Kurnik BR, Kurnik PB, Weisberg LS. Increased renal production of transforming growth factor-beta1 in patients with type II diabetes. Diabetes. 1997 May;46(5):854-9. doi: 10.2337/diab.46.5.854.
citation: Shimizu F, Fukagawa M, Yamauchi S, Taniyama M, Komemushi S, Margolin SB, Kurokawa K: Pirfenidone prevents the progression of irreversible glomerular sclerotic lesions in rats. Nephrology 3:315-322, 1997
citation: Shimizu T, Fukagawa M, Kuroda T, Hata S, Iwasaki Y, Nemoto M, Shirai K, Yamauchi S, Margolin SB, Shimizu F, Kurokawa K. Pirfenidone prevents collagen accumulation in the remnant kidney in rats with partial nephrectomy. Kidney Int Suppl. 1997 Dec;63:S239-43.
citation: Iyer SN, Gurujeyalakshmi G, Giri SN. Effects of pirfenidone on transforming growth factor-beta gene expression at the transcriptional level in bleomycin hamster model of lung fibrosis. J Pharmacol Exp Ther. 1999 Oct;291(1):367-73.
citation: McGowan T, Dunn SR, Sharma K: Treatment of db/db mice with pirfenidone leads to improved histology and serum creatinine. J Am Soc Nephrology 11:A2814, 2000
citation: Raghu G, Johnson WC, Lockhart D, Mageto Y. Treatment of idiopathic pulmonary fibrosis with a new antifibrotic agent, pirfenidone: results of a prospective, open-label Phase II study. Am J Respir Crit Care Med. 1999 Apr;159(4 Pt 1):1061-9. doi: 10.1164/ajrccm.159.4.9805017.