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

Phase 2

Completed

• Conditions: Non-alcoholic Fatty Liver Disease
• Interventions: Drug: Placebo; Drug: Oltipraz

• Registration Number: NCT01373554
• Lead Sponsor: PharmaKing

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-05
• Study First Submitted: 2011-06-03
• Study First Submitted QC: 2011-06-13
• Study First Posted: 2011-06-15
• Primary Completion: 2013-06
• Study Completion: 2013-10
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-08
• Last Update Posted: 2013-12-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	-
Oltipraz	Oltipraz	-

Primary Outcome Measures

Name	Time	Method
MRS	24 weeks	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

Secondary Outcome Measures

Name	Time	Method
change in Cholesterol, Triglyceride	24 weeks
change in BMI	24 weeks
changes in NAS	24 weeks	Subjects with liver biopsy:
change in HOMA-IR	24 weeks
change in ALT, AST and total bilirubin	24 weeks

Trial Locations

Locations (5)

Seoul National University Hospital; 🇰🇷 Daehak-ro Jongno-gu, Seoul, Korea, Republic of

Inje University Ilsan Paik Hospital; 🇰🇷 Dahwa-dong, Ilsanseo-gu, Goyang-si, Gyeonggi-do, Korea, Republic of

Korea University Guro hospital; 🇰🇷 Gurodong-ro, Seoul, Korea, Republic of

Boramae Hospital; 🇰🇷 Sindaebang-dong Dongjak-gu, Seoul, Korea, Republic of

NHUS Ilsan Hospital; 🇰🇷 Ilsan-ro Ilsan-donggu, Goyang-si, Korea, Republic of