Efficacy and Safety of Oltipraz in the Patients With Non-alcoholic Fatty Liver Disease

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, A Multicenter, Randomized, Double-blind, Placebo-controlled, 3 Parallel Groups, Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Oltipraz in Patients With Non-alcoholic Fatty Liver Disease (Except Liver Cirrhosis)

Conditions
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Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: Placebo
* Drug: Oltipraz


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients over 18, under 75 years of age Patients with non-alcoholic fatty liver disease Exclusion Criteria: Over 2 ratio of AST to ALT Type 1 diabetes mellitus (insulin-dependent diabetes mellitus) Disorder in liver function with an exception of non-alcoholic fatty liver (e.g. Virus infection, biliary atresia, autoimmune hepatitis and etc.) Patients who have been taken drugs induced fatty liver for over 3 month within 1 year of participation in this study; amiodarone, tamoxifen, methotrexate, tetracyclines, glucocorticoids, anabolic steroids, over usual dose of estrogen for hormone replacement therapy and valproate Patients who has been taken any medications that could affect the treatment for non-alcoholic steatohepatitis: insulin, insulin sensitizer(metformin, thiazolidinedione), high dose of vitamin E, high dose of UDCA, pentoxifylline, SAM-e, Betaine, types of Statin, types of fibrate and orlistat 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; hepatic cirrhosis, Wilson's disease, malignant tumor, serious metabolic disease, severe renal disease, severe pulmonary disease, severe cardiovascular disease, severe nervous disease/psychiatric disorder, muscle disease and etc Any history of immune disorder which affect the changes in cytokine: inflammatory bowel disease, autoimmune thrombocytopenic purpura, system lupus erythematosus, autoimmune hemolytic anemia, severe psoriasis, rheumatic arthritis and etc 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 Patient who considered ineligible for participation in the study as Investigator's judgment

Ages Eligible for Study
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Minimum Age: 18 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* 30mig/bid or 60mg/bid P.O<br>|
| Experimental: Oltipraz<br> | Drug: Oltipraz<br>* 30mig/bid or 60mg/bid P.O<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MRS | To evaluate the efficacy of the Oltipraz on change in quantity of liver fat concentration assessed by MRS from baseline to 24 weeks in patients with non-alcoholic fatty liver disease | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in ALT, AST and total bilirubin |  | 24 weeks | 
| change in Cholesterol, Triglyceride |  | 24 weeks | 
| change in HOMA-IR |  | 24 weeks | 
| change in BMI |  | 24 weeks | 
| changes in NAS | Subjects with liver biopsy: | 24 weeks |