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

NCT ID: NCT01373554

Last Updated: 2013-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-05-31

Study Completion Date

2013-10-31

Brief Summary

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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

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Conditions

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Non-alcoholic Fatty Liver Disease

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

30mig/bid or 60mg/bid P.O

Oltipraz

Group Type EXPERIMENTAL

Oltipraz

Intervention Type DRUG

30mig/bid or 60mg/bid P.O

Interventions

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Placebo

30mig/bid or 60mg/bid P.O

Intervention Type DRUG

Oltipraz

30mig/bid or 60mg/bid P.O

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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PharmaKing

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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YoonJun Kim, MD.PhD

Role: PRINCIPAL_INVESTIGATOR

Seoul National University Hospital

Locations

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Inje University Ilsan Paik Hospital

Dahwa-dong, Ilsanseo-gu, Goyang-si, Gyeonggi-do, South Korea

Site Status

NHUS Ilsan Hospital

Ilsan-ro Ilsan-donggu, Goyang-si, South Korea

Site Status

Seoul National University Hospital

Daehak-ro Jongno-gu, Seoul, South Korea

Site Status

Korea University Guro hospital

Gurodong-ro, Seoul, South Korea

Site Status

Boramae Hospital

Sindaebang-dong Dongjak-gu, Seoul, South Korea

Site Status

Countries

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South Korea

References

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Kim SG, Kim YM, Choi YH, Lee MG, Choi JY, Han JY, Cho SH, Jang JW, Um SH, Chon CY, Lee DH, Jang JJ, Yu ES, Lee YS. Pharmacokinetics of oltipraz and its major metabolite (RM) in patients with liver fibrosis or cirrhosis: relationship with suppression of circulating TGF-beta1. Clin Pharmacol Ther. 2010 Sep;88(3):360-8. doi: 10.1038/clpt.2010.89. Epub 2010 Jul 21.

Reference Type BACKGROUND
PMID: 20664537 (View on PubMed)

Kim W, Kim BG, Lee JS, Lee CK, Yeon JE, Chang MS, Kim JH, Kim H, Yi S, Lee J, Cho JY, Kim SG, Lee JH, Kim YJ. Randomised clinical trial: the efficacy and safety of oltipraz, a liver X receptor alpha-inhibitory dithiolethione in patients with non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2017 Apr;45(8):1073-1083. doi: 10.1111/apt.13981. Epub 2017 Feb 22.

Reference Type DERIVED
PMID: 28225186 (View on PubMed)

Other Identifiers

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PMK-N01GI1

Identifier Type: -

Identifier Source: org_study_id