Randomised clinical trial

the efficacy and safety of oltipraz, a liver X receptor alpha-inhibitory dithiolethione in patients with non-alcoholic fatty liver disease

W. Kim, B. G. Kim, J. S. Lee, C. K. Lee, Jong Eun Yeon, M. S. Chang, J. H. Kim, H. Kim, S. Yi, J. Lee, J. Y. Cho, S. G. Kim, J. H. Lee, Y. J. Kim

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Background: Oltipraz is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of liver X receptor alpha (LXR-α). Recent studies demonstrated the disruptive role of oltipraz on LXR-α-dependent lipogenesis in hepatocytes and a high-fat diet mouse model. Aim: To evaluate the efficacy and safety of oltipraz for reducing liver fat in subjects with non-alcoholic fatty liver disease (NAFLD). Methods: We performed a multicentre, double-blind, placebo-controlled, phase II study. Subjects with a liver fat >20% and hypertransaminasemia were randomised to the three groups: placebo (n = 22), 30 mg of oltipraz (n = 22) or 60 mg of oltipraz (n = 24) twice daily for 24 weeks. Changes in the liver fat from baseline to 24 weeks quantified using magnetic resonance spectroscopy were the primary outcome. Results: Compared with the placebo group (−3.2 ± 11.1%), absolute changes in the liver fat content increased in a dose-dependent manner: −7.7 ± 7.0% and −13.9 ± 10.7% for the low-dose and high-dose groups (P = 0.13 and P < 0.01). Per cent reduction in the liver fat content was also significantly greater in the high-dose group than in the placebo group (−34.6 ± 29.4% vs. −0.6 ± 62.9%, P = 0.046). Body mass indices (−1.0 ± 0.9% vs. −0.5 ± 1.4%, P = 0.04) significantly decreased in the high-dose group compared to the placebo group. However, absolute changes in insulin resistance, liver enzymes, lipids and cytokines were not significantly different among groups. The incidence of adverse events was comparable among groups. Conclusions: Twenty-four-week oltipraz treatment significantly reduced the liver fat content in patients with NAFLD. Clinicaltrials.gov (NCT01373554).

Original languageEnglish
Pages (from-to)1073-1083
Number of pages11
JournalAlimentary Pharmacology and Therapeutics
Volume45
Issue number8
DOIs
Publication statusPublished - 2017 Apr 1
Externally publishedYes

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Randomized Controlled Trials
Safety
Fats
Liver
Placebos
Lipogenesis
High Fat Diet
Liver X Receptors
Non-alcoholic Fatty Liver Disease
oltipraz
Insulin Resistance
Hepatocytes
Body Mass Index
Magnetic Resonance Spectroscopy
Cytokines
Lipids
Incidence
Enzymes

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Randomised clinical trial : the efficacy and safety of oltipraz, a liver X receptor alpha-inhibitory dithiolethione in patients with non-alcoholic fatty liver disease. / Kim, W.; Kim, B. G.; Lee, J. S.; Lee, C. K.; Yeon, Jong Eun; Chang, M. S.; Kim, J. H.; Kim, H.; Yi, S.; Lee, J.; Cho, J. Y.; Kim, S. G.; Lee, J. H.; Kim, Y. J.

In: Alimentary Pharmacology and Therapeutics, Vol. 45, No. 8, 01.04.2017, p. 1073-1083.

Research output: Contribution to journalArticle

Kim, W. ; Kim, B. G. ; Lee, J. S. ; Lee, C. K. ; Yeon, Jong Eun ; Chang, M. S. ; Kim, J. H. ; Kim, H. ; Yi, S. ; Lee, J. ; Cho, J. Y. ; Kim, S. G. ; Lee, J. H. ; Kim, Y. J. / Randomised clinical trial : the efficacy and safety of oltipraz, a liver X receptor alpha-inhibitory dithiolethione in patients with non-alcoholic fatty liver disease. In: Alimentary Pharmacology and Therapeutics. 2017 ; Vol. 45, No. 8. pp. 1073-1083.
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abstract = "Background: Oltipraz is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of liver X receptor alpha (LXR-α). Recent studies demonstrated the disruptive role of oltipraz on LXR-α-dependent lipogenesis in hepatocytes and a high-fat diet mouse model. Aim: To evaluate the efficacy and safety of oltipraz for reducing liver fat in subjects with non-alcoholic fatty liver disease (NAFLD). Methods: We performed a multicentre, double-blind, placebo-controlled, phase II study. Subjects with a liver fat >20{\%} and hypertransaminasemia were randomised to the three groups: placebo (n = 22), 30 mg of oltipraz (n = 22) or 60 mg of oltipraz (n = 24) twice daily for 24 weeks. Changes in the liver fat from baseline to 24 weeks quantified using magnetic resonance spectroscopy were the primary outcome. Results: Compared with the placebo group (−3.2 ± 11.1{\%}), absolute changes in the liver fat content increased in a dose-dependent manner: −7.7 ± 7.0{\%} and −13.9 ± 10.7{\%} for the low-dose and high-dose groups (P = 0.13 and P < 0.01). Per cent reduction in the liver fat content was also significantly greater in the high-dose group than in the placebo group (−34.6 ± 29.4{\%} vs. −0.6 ± 62.9{\%}, P = 0.046). Body mass indices (−1.0 ± 0.9{\%} vs. −0.5 ± 1.4{\%}, P = 0.04) significantly decreased in the high-dose group compared to the placebo group. However, absolute changes in insulin resistance, liver enzymes, lipids and cytokines were not significantly different among groups. The incidence of adverse events was comparable among groups. Conclusions: Twenty-four-week oltipraz treatment significantly reduced the liver fat content in patients with NAFLD. Clinicaltrials.gov (NCT01373554).",
author = "W. Kim and Kim, {B. G.} and Lee, {J. S.} and Lee, {C. K.} and Yeon, {Jong Eun} and Chang, {M. S.} and Kim, {J. H.} and H. Kim and S. Yi and J. Lee and Cho, {J. Y.} and Kim, {S. G.} and Lee, {J. H.} and Kim, {Y. J.}",
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AU - Kim, W.

AU - Kim, B. G.

AU - Lee, J. S.

AU - Lee, C. K.

AU - Yeon, Jong Eun

AU - Chang, M. S.

AU - Kim, J. H.

AU - Kim, H.

AU - Yi, S.

AU - Lee, J.

AU - Cho, J. Y.

AU - Kim, S. G.

AU - Lee, J. H.

AU - Kim, Y. J.

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AB - Background: Oltipraz is a synthetic dithiolethione with an antisteatotic effect by inhibiting the activity of liver X receptor alpha (LXR-α). Recent studies demonstrated the disruptive role of oltipraz on LXR-α-dependent lipogenesis in hepatocytes and a high-fat diet mouse model. Aim: To evaluate the efficacy and safety of oltipraz for reducing liver fat in subjects with non-alcoholic fatty liver disease (NAFLD). Methods: We performed a multicentre, double-blind, placebo-controlled, phase II study. Subjects with a liver fat >20% and hypertransaminasemia were randomised to the three groups: placebo (n = 22), 30 mg of oltipraz (n = 22) or 60 mg of oltipraz (n = 24) twice daily for 24 weeks. Changes in the liver fat from baseline to 24 weeks quantified using magnetic resonance spectroscopy were the primary outcome. Results: Compared with the placebo group (−3.2 ± 11.1%), absolute changes in the liver fat content increased in a dose-dependent manner: −7.7 ± 7.0% and −13.9 ± 10.7% for the low-dose and high-dose groups (P = 0.13 and P < 0.01). Per cent reduction in the liver fat content was also significantly greater in the high-dose group than in the placebo group (−34.6 ± 29.4% vs. −0.6 ± 62.9%, P = 0.046). Body mass indices (−1.0 ± 0.9% vs. −0.5 ± 1.4%, P = 0.04) significantly decreased in the high-dose group compared to the placebo group. However, absolute changes in insulin resistance, liver enzymes, lipids and cytokines were not significantly different among groups. The incidence of adverse events was comparable among groups. Conclusions: Twenty-four-week oltipraz treatment significantly reduced the liver fat content in patients with NAFLD. Clinicaltrials.gov (NCT01373554).

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