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Pioglitazone vs Vitamin E vs Placebo for Treatment of Non-Diabetic Patients With Nonalcoholic Steatohepatitis (PIVENS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00063622
First received: July 1, 2003
Last updated: August 27, 2012
Last verified: August 2012
  Purpose

The purpose of this study is to determine if therapy with pioglitazone or vitamin E will lead to an improvement in liver histology in non-diabetic adult patients with non-alcoholic steatohepatitis (NASH).


Condition Intervention Phase
Liver Diseases
Drug: Pioglitazone
Dietary Supplement: Vitamin E
Drug: Matching placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Clinical Research Network in Nonalcoholic Steatohepatitis: Pioglitazone vs. Vitamin E vs. Placebo for the Treatment of Non-Diabetic Patients With Nonalcoholic Steatohepatitis (PIVENS)

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Number of Participants With Improvement in Non-alcoholic Fatty Liver Disease (NAFLD) Activity Defined by Change in Standardized Scoring of Liver Biopsies at Baseline and After 96 Weeks of Treatment. [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Total nonalcoholic fatty liver disease (NAFLD) activity was assessed on a scale of 0 to 8, with higher scores indicating more severe disease; the components of this measure include steatosis (assessed on a scale of 0 to 3), lobular inflammation (assessed on a scale of 0 to 3), and hepatocellular ballooning (assessed on a scale of 0 to 2). The primary outcome was an improvement in histological findings from baseline to 96 weeks, which required an improvement by 1 or more points in the hepatocellular ballooning score; no increase in the fibrosis score; and either a decrease in the activity score for nonalcoholic fatty liver disease to a score of 3 or less or a decrease in the activity score of at least 2 points, with at least a 1-point decrease in either the lobular inflammation or steatosis score.


Secondary Outcome Measures:
  • Number of Participants With Improvement in Steatosis [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Steatosis is assessed on a scale of 0 to 3 with higher scores indicating more severe steatosis. This secondary outcome measure is the number of participants that experienced a decrease in steatosis score, which indicates improvement in steatosis.

  • Number of Participants With Improvement in Lobular Inflammation [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Lobular inflammation is assessed on a scale of 0 to 3 with higher scores indicating more severe lobular inflammation. This secondary outcome measure is the number of participants that experienced a decrease in lobular inflammation score, which indicates improvement in lobular inflammation.

  • Number of Participants With Improvement in Hepatocellular Ballooning [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Hepatocellular ballooning is assessed on a scale of 0 to 2 with higher scores indicating more severe hepatocellular ballooning. This secondary outcome measure is the number of participants that experienced a decrease in hepatocellular ballooning score, which indicates improvement in hepatocellular ballooning.

  • Number of Participants With Improvement in Fibrosis [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Fibrosis is assessed on a scale of 0 to 4 with higher scores indicating more severe fibrosis. This secondary outcome measure is the number of participants that experienced a decrease in fibrosis score, which indicates improvement in fibrosis.

  • Number of Participants With Resolution of Definite Nonalcoholic Steatohepatitis [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    The criteria for nonalcoholic steatohepatitis was definite or possible steatohepatitis (assessed by a pathologist) with an activity score of 5 or more, or definite steatohepatitis (confirmed by two pathologists) with an activity score of 4. This secondary outcome measure is the number of participants who met this definition at baseline and did not meet this definition after 96 weeks of treatment and thus had a resolution of steatohepatitis.


Enrollment: 247
Study Start Date: January 2005
Study Completion Date: September 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Pioglitazone
Drug: Pioglitazone
30 mg daily
Other Name: Actos
Active Comparator: 2
Vitamin E
Dietary Supplement: Vitamin E
800 IU daily
Other Name: Nature Made
Placebo Comparator: 3
Placebo Pioglitazone or Placebo Vitamin E
Drug: Matching placebo
Daily

Detailed Description:

The purpose of this study is to determine if therapy with pioglitazone or vitamin E will lead to an improvement in liver histology in non-diabetic adult patients with non-alcoholic steatohepatitis (NASH).

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • Histologic evidence of NASH based on a liver biopsy obtained within 6 months of randomization.
  • Age 18 years or older
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00063622

Locations
United States, California
University of California, San Diego
San Diego, California, United States, 92103
University of California, San Francisco
San Francisco, California, United States, 94143
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Missouri
St. Louis University
St. Louis, Missouri, United States, 63110
United States, North Carolina
Duke University Medical Center
Durham, North Carolina, United States, 27710
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44109
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
  More Information

Additional Information:
No publications provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00063622     History of Changes
Other Study ID Numbers: NASH - ADULT (IND)
Study First Received: July 1, 2003
Results First Received: June 14, 2012
Last Updated: August 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Non alcoholic steatohepatitis
Steatohepatitis

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Alpha-Tocopherol
Pioglitazone
Tocopherols
Tocotrienols
Vitamin E
Vitamins
Antioxidants
Growth Substances
Hypoglycemic Agents
Micronutrients
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents

ClinicalTrials.gov processed this record on November 25, 2014