Efficacy and Safety of Oltipraz in the Patients With Non-alcoholic Fatty Liver Disease (PMK-N01GI1)

PharmaKing

Status and phase

Completed

Phase 2

Conditions

Non-alcoholic Fatty Liver Disease

Treatments

Drug: Oltipraz

Drug: Placebo

Study type

Interventional

Funder types

Industry

Identifiers

NCT01373554

PMK-N01GI1

Details and patient eligibility

About

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.

Enrollment

60 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

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