Non-alcholic 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
DRUGOltipraz 1 (90mg)
DRUGPlacebo
DRUGOltipraz 2 (120mg)
Sponsors
PharmaKing
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
19 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| MRS(magnetic resonance spectroscopy) | 24 weeks | 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. |
Secondary
| Measure | 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 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 |
| change in ALT, AST, γ-GT | 8, 16, 24 weeks |
Other
| Measure | Time frame |
|---|---|
| change in Adipokine, CK-18 | 8, 16, 24 weeks |
Countries
South Korea
Outcome results
None listed