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Liver DiseasesPhase 3PIVENSNCT00063622

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

A Phase 3 study testing Pioglitazone and Vitamin E in people with Liver Diseases, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 8 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Liver Diseases
What is being tested?
Pioglitazone and Vitamin E
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
247 participants
Where
8 sitesUnited States
Study dates
Jan 2005to Sep 2009
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult
  • Histologic evidence of NASH based on a liver biopsy obtained within 6 months of randomization.
  • Age 18 years or older

Trial locations and contacts

8 sites in 1 country.

8 sites in 1 country

United States8 sites

  • Case Western Reserve University

    Cleveland, Ohio, 44109

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Indiana University

    Indianapolis, Indiana, 46202

  • Virginia Commonwealth University

    Richmond, Virginia, 23298

  • University of California, San Diego

    San Diego, California, 92103

  • University of California, San Francisco

    San Francisco, California, 94143

  • University of Washington

    Seattle, Washington, 98195

  • St. Louis University

    St Louis, Missouri, 63110

Other trials in United States

About this study

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)

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).

Read the 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).

Conditions
Liver Diseases
Being tested
Pioglitazone, Vitamin E, Matching placebo
Keywords
Non alcoholic steatohepatitis, Steatohepatitis
Medical subject headings
Liver Diseases, Non-alcoholic Fatty Liver Disease, Fatty Liver

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PioglitazoneDrug

    Also called Actos

    30 mg daily

  • Vitamin EDietary supplement

    Also called Nature Made

    800 IU daily

  • Matching placeboDrug

    Daily

Study groups in NCT00063622
Study groupRoleWhat they receive
1Active comparatorPioglitazone
Receives: Drug: Pioglitazone
2Active comparatorVitamin E
Receives: Dietary Supplement: Vitamin E
3Placebo comparatorPlacebo Pioglitazone or Placebo Vitamin E
Receives: Drug: Matching placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: baseline and 96 weeks

Secondary outcomes (5)

  1. Number of Participants With Improvement in Steatosis

    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.

    Measured: baseline and 96 weeks

  2. Number of Participants With Improvement in Lobular Inflammation

    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.

    Measured: baseline and 96 weeks

  3. Number of Participants With Improvement in Hepatocellular Ballooning

    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.

    Measured: baseline and 96 weeks

  4. Number of Participants With Improvement in Fibrosis

    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.

    Measured: baseline and 96 weeks

  5. Number of Participants With Resolution of Definite Nonalcoholic Steatohepatitis

    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.

    Measured: baseline and 96 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Jul 2003 (estimated)
  2. Study startJan 2005
  3. Primary completionJun 2009
  4. Study completionSep 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
247 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00063622
Sponsor's protocol ID
NASH - ADULT (IND)
Other IDs
U01DK061730
Acronym
PIVENS
Status last verified
Aug 2012
First submitted
1 Jul 2003
Last updated
6 Apr 2018
Data monitoring committee
Yes

Publications

  • Hakim A, Lin KH, Schwantes-An TH, Abreu M, Tan J, Guo X, Yates KP, Lotta L, Verweij N, Loomba R, Kleiner DE, Schwimmer JB, Rotter JI, Chalasani NP. A comprehensive evaluation of candidate genetic polymorphisms in a large histologically characterized MASLD cohort using a novel framework. Hepatol Commun. 2025 May 29;9(6):e0728. doi: 10.1097/HC9.0000000000000728. eCollection 2025 Jun 1.

    PubMed 40434633

  • 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.

    PubMed 37933187

  • 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.

    PubMed 33454241

  • 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.

    PubMed 32337059

  • 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.

    PubMed 27933201

  • 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.

    PubMed 25429853

  • 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.

    PubMed 24849310

  • 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.

    PubMed 23718573

  • 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.

    PubMed 22338037

  • 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.

    PubMed 20427778

  • 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.

    PubMed 18804555

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Pioglitazone and Vitamin E in people with Liver Diseases, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 8 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Apr 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00063622, which also lists 11 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Apr 2018.

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