Pirfenidone: A New Drug to Treat Kidney Disease in Patients With Diabetes

Diabetes Mellitus Clinical Trial

Official title:

Pirfenidone: A Novel Anti-Scarring Therapy for Diabetic Nephropathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00063583
• Other study ID #: 1-RO1-DK63017-01
• Secondary ID: R01DK063017
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: June 30, 2003
• Last updated: November 3, 2009
• Start date: June 2003
• Est. completion date: March 2009

Study information

• Verified date: November 2009
• Source: Sharma, Kumar, M.D.
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00105391

Recruitment information / eligibility

• Status: Completed
• Enrollment: 77
• Est. completion date: March 2009
• Est. primary completion date: November 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetic Nephropathies
• Diabetic Nephropathy
• Kidney Diseases

Intervention

Drug:
• Pirfenidone
Pirfenidone will be administered orally at 1200 or 2400 mg day in divided doses

Locations

Country	Name	City	State
United States	National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)	Bethesda	Maryland
United States	The Center for Diabetic Kidney Disease at Thomas Jefferson University	Philadelphia	Pennsylvania
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (3)

Lead Sponsor	Collaborator
Sharma, Kumar, M.D.	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

References & Publications (6)

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. — View 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

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. — View 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. — View 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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary endpoint will be the change in renal function from baseline to the end of the study period (12 months).		12 months	No
Secondary	% change in urine albumin excretion from baseline to end of study period.		12 months	No
Secondary	% change in levels of TGF-b1 in urine, plasma and serum from baseline to end of study period.		12 months	No
Secondary	• Determine the relationship between % change in TGF-b1 levels and the change in GFR		12 months	No