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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01373554
Recruitment Status : Completed
First Posted : June 15, 2011
Last Update Posted : December 10, 2013
Information provided by (Responsible Party):

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.

Condition or disease Intervention/treatment Phase
Non-alcoholic Fatty Liver Disease Drug: Placebo Drug: Oltipraz Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Multicenter, Randomized, Double-blind, Placebo-controlled, A Multicenter, Randomized, Double-blind, Placebo-controlled, 3 Parallel Groups, Phase 2 Study to Evaluate the Efficacy, Safety and Pharmacokinetics of Oltipraz in Patients With Non-alcoholic Fatty Liver Disease (Except Liver Cirrhosis)
Study Start Date : May 2011
Actual Primary Completion Date : June 2013
Actual Study Completion Date : October 2013

Arm Intervention/treatment
Placebo Comparator: Placebo Drug: Placebo
30mig/bid or 60mg/bid P.O

Experimental: Oltipraz Drug: Oltipraz
30mig/bid or 60mg/bid P.O

Primary Outcome Measures :
  1. MRS [ Time Frame: 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 Outcome Measures :
  1. change in ALT, AST and total bilirubin [ Time Frame: 24 weeks ]
  2. change in Cholesterol, Triglyceride [ Time Frame: 24 weeks ]
  3. change in HOMA-IR [ Time Frame: 24 weeks ]
  4. change in BMI [ Time Frame: 24 weeks ]
  5. changes in NAS [ Time Frame: 24 weeks ]
    Subjects with liver biopsy:

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01373554

Korea, Republic of
Inje University Ilsan Paik Hospital
Dahwa-dong, Ilsanseo-gu, Goyang-si, Gyeonggi-do, Korea, Republic of, 411-706
NHUS Ilsan Hospital
Ilsan-ro Ilsan-donggu, Goyang-si, Korea, Republic of, 410-719
Seoul National University Hospital
Daehak-ro Jongno-gu, Seoul, Korea, Republic of, 110-744
Korea University Guro hospital
Gurodong-ro, Seoul, Korea, Republic of, 152-703
Boramae Hospital
Sindaebang-dong Dongjak-gu, Seoul, Korea, Republic of, 156-707
Sponsors and Collaborators
Principal Investigator: YoonJun Kim, MD.PhD Seoul National University Hospital

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: PharmaKing Identifier: NCT01373554     History of Changes
Other Study ID Numbers: PMK-N01GI1
First Posted: June 15, 2011    Key Record Dates
Last Update Posted: December 10, 2013
Last Verified: December 2013

Additional relevant MeSH terms:
Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases
Antiviral Agents
Anti-Infective Agents
Antiplatyhelmintic Agents
Antiparasitic Agents
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Antineoplastic Agents
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Retroviral Agents