Non-alcoholic Fatty Liver Disease
Conditions
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.
Interventions
DRUGPlacebo
30mig/bid or 60mg/bid P.O
DRUGOltipraz
30mig/bid or 60mg/bid P.O
Sponsors
PharmaKing
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 | — |
| change in Cholesterol, Triglyceride | 24 weeks | — |
Countries
South Korea
Outcome results
None listed