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| ID | Type | Description | Link |
|---|---|---|---|
| U01DK061730 | U.S. NIH Grant/Contract | View source |
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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).
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).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | Pioglitazone |
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| 2 | Active Comparator | Vitamin E |
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| 3 | Placebo Comparator | Placebo Pioglitazone or Placebo Vitamin E |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Pioglitazone | Drug | 30 mg daily |
|
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| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | baseline and 96 weeks |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California, San Diego | San Diego | California | 92103 | United States | ||
| University of California, San Francisco |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37933187 | Derived | 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. | |
| 33454241 | Derived | 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. |
| Label | URL |
|---|---|
| National Institute of Diabetes and Digestive and Kidney Diseases | View source |
Not provided
A total of 339 patients were registered and screened for PIVENS trial, 92 of whom (27%) were found ineligible. The failure to meet histological entry criteria and fasting blood glucose >125 mg/dL were the most frequent reasons for ineligibility.
PIVENS enrollment started in January 2005 and ended in January 2007.
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| ID | Title | Description |
|---|---|---|
| FG000 | Pioglitazone | Pioglitazone at a dose of 30 mg daily |
| FG001 | Vitamin E | Vitamin E at a dose of 800 IU daily |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Vitamin E |
| Dietary Supplement |
800 IU daily |
|
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| Matching placebo | Drug | Daily |
|
| 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. |
| baseline and 96 weeks |
| 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. | baseline and 96 weeks |
| 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. | baseline and 96 weeks |
| 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. | baseline and 96 weeks |
| San Francisco |
| California |
| 94143 |
| United States |
| Indiana University | Indianapolis | Indiana | 46202 | United States |
| St. Louis University | St Louis | Missouri | 63110 | United States |
| Duke University Medical Center | Durham | North Carolina | 27710 | United States |
| Case Western Reserve University | Cleveland | Ohio | 44109 | United States |
| Virginia Commonwealth University | Richmond | Virginia | 23298 | United States |
| University of Washington | Seattle | Washington | 98195 | United States |
| 32337059 | Derived | 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. |
| 27933201 | Derived | 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. |
| 25429853 | Derived | 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. |
| 24849310 | Derived | 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. |
| 23718573 | Derived | 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. |
| 22338037 | Derived | 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. |
| 20427778 | Derived | 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. |
| 18804555 | Derived | 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. |
| FG002 |
| Placebo |
Placebo Pioglitazone and Placebo Vitamin E |
| COMPLETED |
|
| NOT COMPLETED |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Pioglitazone | Pioglitazone at a dose of 30 mg daily |
| BG001 | Vitamin E | Vitamin E at a dose of 800 IU daily |
| BG002 | Placebo | Placebo Pioglitazone and Placebo Vitamin E |
| BG003 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Number | participants |
| ||||||||||||||||
| Total nonalcoholic fatty liver disease (NAFLD) activity score | 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). | Mean | Standard Deviation | scores on a scale |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | All randomized participants were included in the analysis of the primary outcome. | Posted | Number | participants | baseline and 96 weeks |
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| Secondary | 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. | Number of subjects with biopsy specimens at baseline and 96 weeks | Posted | Number | participants | baseline and 96 weeks |
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| Secondary | 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. | Number of subjects with biopsy specimens at baseline and 96 weeks | Posted | Number | participants | baseline and 96 weeks |
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| Secondary | 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. | Number of subjects with biopsy specimens at baseline and 96 weeks | Posted | Number | participants | baseline and 96 weeks |
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| Secondary | 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. | Number of subjects with biopsy specimens at baseline and 96 weeks | Posted | Number | participants | baseline and 96 weeks |
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| Secondary | 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. | Number of subjects with biopsy specimens at baseline and 96 weeks | Posted | Number | participants | baseline and 96 weeks |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Pioglitazone | Pioglitazone at a dose of 30 mg daily | 2 | 80 | 41 | 80 | ||
| EG001 | Vitamin E | Vitamin E at a dose of 800 IU daily | 7 | 84 | 46 | 84 | ||
| EG002 | Placebo | Placebo Pioglitazone and Placebo Vitamin E | 10 | 83 | 40 | 83 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Severe adverse event | General disorders |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiovascular Event | Cardiac disorders |
| |||
| Bone fracture | Musculoskeletal and connective tissue disorders |
| |||
| Diabetes | Endocrine disorders |
| |||
| Cirrhosis | Hepatobiliary disorders |
| |||
| Other mild and moderate adverse event | General disorders |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Arun J. Sanyal | Virginia Commonwealth University | asanyal@mcvh-vcu.edu |
| ID | Term |
|---|---|
| D008107 | Liver Diseases |
| D065626 | Non-alcoholic Fatty Liver Disease |
| D005234 | Fatty Liver |
| ID | Term |
|---|---|
| D004066 | Digestive System Diseases |
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| ID | Term |
|---|---|
| D000077205 | Pioglitazone |
| D014810 | Vitamin E |
| ID | Term |
|---|---|
| D045162 | Thiazolidinediones |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D001578 | Benzopyrans |
| D011714 | Pyrans |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
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| Male |
|
| The proportions in each active-treatment group (pioglitazone and vitamin E) in whom there was improvement in non-alcoholic steatohepatitis were compared with the proportion of subjects in the placebo group in whom there was improvement. | Mantel Haenszel | 0.04 | Given the fact that there were two planned primary comparisons, Bonferroni-adjusted P values of less than 0.025 were considered to indicate statistical significance. | Superiority or Other |
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