TY - JOUR
T1 - Role of Vitamin E for nonalcoholic steatohepatitis in patients with type 2 diabetes
T2 - A randomized controlled trial
AU - Bril, Fernando
AU - Biernacki, Diane M.
AU - Kalavalapalli, Srilaxmi
AU - Lomonaco, Romina
AU - Subbarayan, Sreevidya K.
AU - Lai, Jinping
AU - Tio, Fermin
AU - Suman, Amitabh
AU - Orsak, Beverly K.
AU - Hecht, Joan
AU - Cusi, Kenneth
N1 - Funding Information:
This was an investigator-initiated, mul ticenter, parallel-group, double-blind, randomized (1:1:1 allocation), placebo- controlled trial conducted between June 2010 and September 2016 in a U.S. De partment of Veterans Affairs (VA) pop ulation. The institutional review boards of the University of Florida and the University of Texas Health Science Center at San Antonio approved the study, and all subjects provided written informed consent before participation. The study always included three arms as described in the original protocol. This was supported by procurement of study medication and independent randomization schedule by the VA research pharmacy, as well as supervision by an external and independent committee (VA Clinical Science Research and Development Data Monitoring Committee), which convened quarterly to assess patient recruitment and adverse event reports and ensure the safety of study participants. However, this was not clear in the original ClinicalTrials.gov registration because of clerical errors, which led to inaccurate study registration in 2009–2010 regarding the three arms of the study.
Funding Information:
Funding. This work was supported by a U.S. Department of Veterans Affairs Merit Award (1 I01 CX000167-01 to K.C.).
Publisher Copyright:
© 2019 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.
PY - 2019/8/1
Y1 - 2019/8/1
N2 - OBJECTIVE While vitamin E has shown to improve nonalcoholic steatohepatitis (NASH) in patients without diabetes, information on patients with type 2 diabetes mellitus (T2DM) is lacking. The aim of this study was to determine whether vitamin E, alone or combined with pioglitazone, improves histology in patients with T2DM and NASH. RESEARCH DESIGN AND METHODS This was a proof-of-concept, randomized, double-blind, placebo-controlled trial conducted from 2010 to 2016. Patients with T2DM and biopsy-proven NASH (n = 105) were randomized to vitamin E 400 IU b.i.d., vitamin E 400 IU b.i.d. plus pioglitazone 45 mg/day, or placebo. Eighty-six patients completed the 18-month study. The primary end point was a two-point reduction in the nonalcoholic fatty liver disease activity score from two different parameters, without worsening of fibrosis. Secondary outcomes were resolution of NASH without worsening of fibrosis, individual histological scores, and metabolic parameters. RESULTS More patients on combination therapy achieved the primary outcome versus placebo (54% vs. 19%, P = 0.003) but not with vitamin E alone (31% vs. 19%, P = 0.26). Both groups showed improvements in resolution of NASH compared with placebo (combination group: 43% vs. 12%, P = 0.005; vitamin E alone: 33% vs. 12%, P = 0.04). While steatosis assessed by histology improved with combination therapy (P < 0.001) and vitamin E alone (P = 0.018), inflammation (P = 0.018) and ballooning (P = 0.022) only improved with combination therapy. No improvement in fibrosis was observed in any group. CONCLUSIONS In this proof-of-concept study, combination therapy was better than placebo in improving liver histology in patients with NASH and T2DM. Vitamin E alone did not significantly change the primary histological outcome.
AB - OBJECTIVE While vitamin E has shown to improve nonalcoholic steatohepatitis (NASH) in patients without diabetes, information on patients with type 2 diabetes mellitus (T2DM) is lacking. The aim of this study was to determine whether vitamin E, alone or combined with pioglitazone, improves histology in patients with T2DM and NASH. RESEARCH DESIGN AND METHODS This was a proof-of-concept, randomized, double-blind, placebo-controlled trial conducted from 2010 to 2016. Patients with T2DM and biopsy-proven NASH (n = 105) were randomized to vitamin E 400 IU b.i.d., vitamin E 400 IU b.i.d. plus pioglitazone 45 mg/day, or placebo. Eighty-six patients completed the 18-month study. The primary end point was a two-point reduction in the nonalcoholic fatty liver disease activity score from two different parameters, without worsening of fibrosis. Secondary outcomes were resolution of NASH without worsening of fibrosis, individual histological scores, and metabolic parameters. RESULTS More patients on combination therapy achieved the primary outcome versus placebo (54% vs. 19%, P = 0.003) but not with vitamin E alone (31% vs. 19%, P = 0.26). Both groups showed improvements in resolution of NASH compared with placebo (combination group: 43% vs. 12%, P = 0.005; vitamin E alone: 33% vs. 12%, P = 0.04). While steatosis assessed by histology improved with combination therapy (P < 0.001) and vitamin E alone (P = 0.018), inflammation (P = 0.018) and ballooning (P = 0.022) only improved with combination therapy. No improvement in fibrosis was observed in any group. CONCLUSIONS In this proof-of-concept study, combination therapy was better than placebo in improving liver histology in patients with NASH and T2DM. Vitamin E alone did not significantly change the primary histological outcome.
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U2 - 10.2337/dc19-0167
DO - 10.2337/dc19-0167
M3 - Article
C2 - 31332029
AN - SCOPUS:85068741317
VL - 42
SP - 1481
EP - 1488
JO - Diabetes Care
JF - Diabetes Care
SN - 1935-5548
IS - 8
ER -