Clinical trial NCT00063622: Pioglitazone vs Vitamin E vs Placebo for Treatment of Non-Diabetic Patients With Nonalcoholic Steatohepatitis (PIVENS)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Liver Diseases
Keywords: Non alcoholic steatohepatitis
Steatohepatitis
Lead sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Sponsor class: NIH
First posted: 2003-07-03
Enrollment: 247
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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 criteria: * Histologic evidence of NASH based on a liver biopsy obtained within 6 months of randomization.
* Age 18 years or older

Primary outcomes:
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.
timeFrame: baseline and 96 weeks
Secondary outcomes:
measure: Number of Participants With Improvement in Steatosis
timeFrame: baseline and 96 weeks
measure: Number of Participants With Improvement in Lobular Inflammation
timeFrame: baseline and 96 weeks
measure: Number of Participants With Improvement in Hepatocellular Ballooning
timeFrame: baseline and 96 weeks
measure: Number of Participants With Improvement in Fibrosis
timeFrame: baseline and 96 weeks
measure: Number of Participants With Resolution of Definite Nonalcoholic Steatohepatitis
timeFrame: baseline and 96 weeks
Other outcomes:
Locations:
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Saint Louis
country: United States
facility: St. Louis University
state: Missouri
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve University
state: Ohio
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.