Clinical trial NCT02068339: Efficacy and Safety of Oltipraz for Liver Fat Reduction in Patients With Non-Alcoholic Fatty Liver Disease Except for Liver Cirrhosis
Official title: A Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Phase 3 Clinical Trial to Evaluate the Efficacy and Safety of Oltipraz for Liver Fat Reduction in Patients With Non-Alcoholic Fatty Liver Disease Except for Liver Cirrhosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-alcholic Fatty Liver Disease
Lead sponsor: PharmaKing
Sponsor class: INDUSTRY
First posted: 2014-02-21
Enrollment: 283
Sex: ALL
Minimum age (years): 19
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: MRS(magnetic resonance spectroscopy)
timeFrame: 24 weeks
Secondary outcomes:
measure: change in liver fat concentration
timeFrame: 24 weeks
measure: change in BMI
timeFrame: 8, 16, 24 weeks
measure: change in NAFLD Fibrosis score (NFS)
timeFrame: 24 weeks
measure: change in ALT, AST, γ-GT
timeFrame: 8, 16, 24 weeks
measure: change in Cholesterol (total, LDL, HDL, VLDL), Triglyceride (TG)
timeFrame: 8, 16, 24 weeks
measure: change in HOMA-IR
timeFrame: 8, 16, 24 weeks
measure: change in waist circumference
timeFrame: 24 weeks
Other outcomes:
measure: change in Adipokine, CK-18
timeFrame: 8, 16, 24 weeks
Locations:
city: Ilsan-ro Ilsan-donggu
country: Korea, Republic of
facility: NHUS Ilsan Hospital
state: Goyang-si
city: Dahwa-dong, Ilsanseo-gu, Goyang-si
country: Korea, Republic of
facility: Inje University Ilsan Paik Hospital
state: Gyeonggi-do
city: Daehak-ro Jongno-gu
country: Korea, Republic of
facility: Seoul National University Hospital
state: Seoul
city: Gurodong-ro
country: Korea, Republic of
facility: Korea University Guro hospital
state: Seoul
city: Sindaebang-dong Dongjak-gu
country: Korea, Republic of
facility: Boramae Hospital
state: Seoul
Study officials:
References: