Efficacy and Safety of Oltipraz for Liver Fat Reduction in Patients With Non-Alcoholic Fatty Liver Disease Except for Liver Cirrhosis

Study Overview
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Brief Summary
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Dithiolethiones, a novel class of adenosine monophosphate-activated protein kinase (AMPK) activators, prevent insulin resistance through AMPK-dependent p70 ribosomal S6 kinase-1 (S6K1) inhibition. And it is well known that the modulation of S6K1 by oltipraz inhibited the development of insulin resistance and hyperglycemia through the AMPK-S6K1 pathway.Also some research reported that LXRg (a member of the nuclear hormone receptor)-mediated increases in SREBP-1c (the sterol regulatory element-binding protein-1c gene) promote the expression of lipogenic genes and enhance fatty acid synthesis and oltipraz inhibits LXRg and SREBP-c. Therefore, Oltipraz inhibits fatty acid synthesis through AMPK-S6K1 pathway and LXRg-SREBP-1c pathway in liver.

Official Title
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A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of Oltipraz for Liver Fat Reduction in Patients With Non-Alcoholic Fatty Liver Disease Except for Liver Cirrhosis

Conditions
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Non-alcholic Fatty Liver Disease

Intervention / Treatment
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* Drug: Oltipraz 1 (90mg)
* Drug: Placebo
* Drug: Oltipraz 2 (120mg)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 19 under 75 years of age Patients with non-alcoholic fatty liver disease except for cirrhosis Patients who have abnormal ALT, AST Patients who are satisfied with laboratory test Patients who agree to contraception Patients who can keet the diet Exclusion Criteria: Over 2 ratio of AST to ALT Type 1 diabetes mellitus (insulin-dependent diabetes mellitus) or Type 2 diabetes mellitus(not controlled) Disorder in liver function with an exception of non-alcoholic fatty liver Patients with malignant tumors Patients who have been taken drugs induced fatty liver within 8 weeks of participation in this study Patients who has been taken any medications that could affect the treatment for NAFLD within 4 weeks Patients who have been taken Vitamin E (≥ 800 IU/day), thiazolidinediones, orlistat within 12 weeks Patients who had a Bariatric surgery less than 6 month prior to the participation in the study Patients who are judged by investigator that participation of the study is difficult due to disease as follow; Any history of immune disorder Patients who have received treatment that may affect liver function within 1 month prior to the participation in the study Patient who has been administered other investigational product within 1 month prior to the participation in the study Patient who is not allowed to get MRS test: pacemaker, shunt and etc Pregnant or nursing women anti-HIV antibody (+) Patient who considered ineligible for participation in the study as Investigator's judgment

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo Comparator / Tid (total 0mg) | Drug: Placebo<br> <br> |
| Experimental: Oltipraz 1<br>Total 90mg, by mouth, tid | Drug: Oltipraz 1 (90mg)<br> <br> |
| Experimental: Oltipraz 2<br>Total 120mg, by mouth, tid | Drug: Oltipraz 2 (120mg)<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRS(magnetic resonance spectroscopy) | To evaluate the efficacy of the Oltipraz on change in quantity of liver fat (% change) assessed by MRS from baseline to 24 weeks in patients. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in liver fat concentration |  | 24 weeks | 
| change in BMI |  | 8, 16, 24 weeks | 
| change in NAFLD Fibrosis score (NFS) |  | 24 weeks | 
| change in ALT, AST, γ-GT |  | 8, 16, 24 weeks | 
| change in Cholesterol (total, LDL, HDL, VLDL), Triglyceride (TG) |  | 8, 16, 24 weeks | 
| change in HOMA-IR |  | 8, 16, 24 weeks | 
| change in waist circumference |  | 24 weeks |