NCT00063622

Brief Summary

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).

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
247

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jan 2005

Longer than P75 for phase_3

Geographic Reach
1 country

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 1, 2003

Completed
2 days until next milestone

First Posted

Study publicly available on registry

July 3, 2003

Completed
1.5 years until next milestone

Study Start

First participant enrolled

January 1, 2005

Completed
4.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2009

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2009

Completed
2.9 years until next milestone

Results Posted

Study results publicly available

August 1, 2012

Completed
Last Updated

April 6, 2018

Status Verified

August 1, 2012

Enrollment Period

4.4 years

First QC Date

July 1, 2003

Results QC Date

June 14, 2012

Last Update Submit

March 12, 2018

Conditions

Liver Diseases

Keywords

Non alcoholic steatohepatitisSteatohepatitis

Outcome Measures

Primary Outcomes (1)

  • 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.

    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.

    baseline and 96 weeks

Secondary Outcomes (5)

  • Number of Participants With Improvement in Steatosis

    baseline and 96 weeks

  • Number of Participants With Improvement in Lobular Inflammation

    baseline and 96 weeks

  • Number of Participants With Improvement in Hepatocellular Ballooning

    baseline and 96 weeks

  • Number of Participants With Improvement in Fibrosis

    baseline and 96 weeks

  • Number of Participants With Resolution of Definite Nonalcoholic Steatohepatitis

    baseline and 96 weeks

Study Arms (3)

1

ACTIVE COMPARATOR

Pioglitazone

Drug: Pioglitazone

2

ACTIVE COMPARATOR

Vitamin E

Dietary Supplement: Vitamin E

3

PLACEBO COMPARATOR

Placebo Pioglitazone or Placebo Vitamin E

Drug: Matching placebo

Interventions

PioglitazoneDRUG

30 mg daily

Also known as: Actos
1
Vitamin EDIETARY_SUPPLEMENT

800 IU daily

Also known as: Nature Made
2
Matching placeboDRUG

Daily

3

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
* Histologic evidence of NASH based on a liver biopsy obtained within 6 months of randomization. * Age 18 years or older

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (8)

University of California, San Diego

San Diego, California, 92103, United States

Location

University of California, San Francisco

San Francisco, California, 94143, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

St. Louis University

St Louis, Missouri, 63110, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Case Western Reserve University

Cleveland, Ohio, 44109, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23298, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

Related Publications (10)

  • Shinde S, Nelson DR, Mitroi J, Heaton PC, Hincapie AL, Brouwers B. The roles of type 2 diabetes and obesity in disease activity and progression of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis. Curr Med Res Opin. 2024 Jan;40(1):59-68. doi: 10.1080/03007995.2023.2279676. Epub 2024 Jan 3.

    PMID: 37933187DERIVED

  • Vilar-Gomez E, Gawrieh S, Liang T, McIntyre AD, Hegele RA, Chalasani N. Interrogation of selected genes influencing serum LDL-Cholesterol levels in patients with well characterized NAFLD. J Clin Lipidol. 2021 Mar-Apr;15(2):275-291. doi: 10.1016/j.jacl.2020.12.010. Epub 2020 Dec 27.

    PMID: 33454241DERIVED

  • Maev IV, Samsonov AA, Palgova LK, Pavlov CS, Shirokova EN, Vovk EI, Starostin KM. Effectiveness of phosphatidylcholine as adjunctive therapy in improving liver function tests in patients with non-alcoholic fatty liver disease and metabolic comorbidities: real-life observational study from Russia. BMJ Open Gastroenterol. 2020 Mar 26;7(1):e000368. doi: 10.1136/bmjgast-2019-000368. eCollection 2020.

    PMID: 32337059DERIVED

  • Kanwar P, Nelson JE, Yates K, Kleiner DE, Unalp-Arida A, Kowdley KV. Association between metabolic syndrome and liver histology among NAFLD patients without diabetes. BMJ Open Gastroenterol. 2016 Nov 9;3(1):e000114. doi: 10.1136/bmjgast-2016-000114. eCollection 2016.

    PMID: 27933201DERIVED

  • Corey KE, Vuppalanchi R, Wilson LA, Cummings OW, Chalasani N; NASH CRN. NASH resolution is associated with improvements in HDL and triglyceride levels but not improvement in LDL or non-HDL-C levels. Aliment Pharmacol Ther. 2015 Feb;41(3):301-9. doi: 10.1111/apt.13035. Epub 2014 Nov 28.

    PMID: 25429853DERIVED

  • Guy CD, Suzuki A, Abdelmalek MF, Burchette JL, Diehl AM; NASH CRN. Treatment response in the PIVENS trial is associated with decreased Hedgehog pathway activity. Hepatology. 2015 Jan;61(1):98-107. doi: 10.1002/hep.27235. Epub 2014 Aug 25.

    PMID: 24849310DERIVED

  • Hoofnagle JH, Van Natta ML, Kleiner DE, Clark JM, Kowdley KV, Loomba R, Neuschwander-Tetri BA, Sanyal AJ, Tonascia J; Non-alcoholic Steatohepatitis Clinical Research Network (NASH CRN). Vitamin E and changes in serum alanine aminotransferase levels in patients with non-alcoholic steatohepatitis. Aliment Pharmacol Ther. 2013 Jul;38(2):134-43. doi: 10.1111/apt.12352. Epub 2013 May 29.

    PMID: 23718573DERIVED

  • Guerrerio AL, Colvin RM, Schwartz AK, Molleston JP, Murray KF, Diehl A, Mohan P, Schwimmer JB, Lavine JE, Torbenson MS, Scheimann AO. Choline intake in a large cohort of patients with nonalcoholic fatty liver disease. Am J Clin Nutr. 2012 Apr;95(4):892-900. doi: 10.3945/ajcn.111.020156. Epub 2012 Feb 15.

    PMID: 22338037DERIVED

  • Sanyal AJ, Chalasani N, Kowdley KV, McCullough A, Diehl AM, Bass NM, Neuschwander-Tetri BA, Lavine JE, Tonascia J, Unalp A, Van Natta M, Clark J, Brunt EM, Kleiner DE, Hoofnagle JH, Robuck PR; NASH CRN. Pioglitazone, vitamin E, or placebo for nonalcoholic steatohepatitis. N Engl J Med. 2010 May 6;362(18):1675-85. doi: 10.1056/NEJMoa0907929. Epub 2010 Apr 28.

    PMID: 20427778DERIVED

  • Chalasani NP, Sanyal AJ, Kowdley KV, Robuck PR, Hoofnagle J, Kleiner DE, Unalp A, Tonascia J; NASH CRN Research Group. Pioglitazone versus vitamin E versus placebo for the treatment of non-diabetic patients with non-alcoholic steatohepatitis: PIVENS trial design. Contemp Clin Trials. 2009 Jan;30(1):88-96. doi: 10.1016/j.cct.2008.09.003. Epub 2008 Sep 10.

    PMID: 18804555DERIVED

Related Links

MeSH Terms

Conditions

Liver DiseasesNon-alcoholic Fatty Liver DiseaseFatty Liver

Interventions

PioglitazoneVitamin E

Condition Hierarchy (Ancestors)

Digestive System Diseases

Intervention Hierarchy (Ancestors)

ThiazolidinedionesThiazolesSulfur CompoundsOrganic ChemicalsAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsBenzopyransPyransHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-Ring

Results Point of Contact

Title
Arun J. Sanyal
Organization
Virginia Commonwealth University
asanyal@mcvh-vcu.edu

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 1, 2003

First Posted

July 3, 2003

Study Start

January 1, 2005

Primary Completion

June 1, 2009

Study Completion

September 1, 2009

Last Updated

April 6, 2018

Results First Posted

August 1, 2012

Record last verified: 2012-08

Locations

US(8)