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

Pirfenidone: A Novel Anti-Scarring Therapy for Diabetic Nephropathy

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus; Diabetic Nephropathy
• Intervention / Treatment: Drug: Pirfenidone

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.

• Study Type: Interventional
• Enrollment (Actual): 77
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institute of Diabetes and Digestive and Kidney Disease (NIDDK)
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • The Center for Diabetic Kidney Disease at Thomas Jefferson University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo	Drug: Pirfenidone; Pirfenidone will be administered orally at 1200 or 2400 mg day in divided doses
EXPERIMENTAL: Pirfenidone 1200 mg/day; Pirfenidone will be administered at a dose of 1200 mg/day	Drug: Pirfenidone; Pirfenidone will be administered orally at 1200 or 2400 mg day in divided doses
EXPERIMENTAL: Pirfenidone 2400 mg/day; Pirfenidone will be administered at 2400 mg/day	Drug: Pirfenidone; Pirfenidone will be administered orally at 1200 or 2400 mg day in divided doses

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The primary endpoint will be the change in renal function from baseline to the end of the study period (12 months).	12 months

Secondary Outcome Measures

Outcome Measure	Time Frame
% change in urine albumin excretion from baseline to end of study period.	12 months
% change in levels of TGF-b1 in urine, plasma and serum from baseline to end of study period.	12 months
• Determine the relationship between % change in TGF-b1 levels and the change in GFR	12 months

Collaborators and Investigators

• Sponsor: Sharma, Kumar, M.D.
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH)
• Investigators: Principal Investigator: Kumar Sharma, M.D., UCSD

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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. doi: 10.1164/ajrccm.159.4.9805017.

Study record dates

Study Major Dates

• Study Start: June 1, 2003
• Primary Completion (ACTUAL): November 1, 2007
• Study Completion (ACTUAL): March 1, 2009

Study Registration Dates

• First Submitted: June 30, 2003
• First Submitted That Met QC Criteria: July 1, 2003
• First Posted (ESTIMATE): July 2, 2003

Study Record Updates

• Last Update Posted (ESTIMATE): November 4, 2009
• Last Update Submitted That Met QC Criteria: November 3, 2009
• Last Verified: November 1, 2009

More Information

Terms related to this study

• Keywords: Kidney disease
• Additional Relevant MeSH Terms: Urologic Diseases; Endocrine System Diseases; Diabetes Complications; Diabetes Mellitus; Kidney Diseases; Diabetic Nephropathies; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Pirfenidone
• Other Study ID Numbers: 1R01DK063017-01 (NIH); R01DK063017 (NIH)