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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
PharmaKing
ClinicalTrials.gov Identifier:
NCT01373554
First received: June 3, 2011
Last updated: December 8, 2013
Last verified: December 2013
  Purpose

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 Intervention Phase
Non-alcoholic Fatty Liver Disease
Drug: Placebo
Drug: Oltipraz
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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)

Resource links provided by NLM:


Further study details as provided by PharmaKing:

Primary Outcome Measures:
  • MRS [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    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:
  • change in ALT, AST and total bilirubin [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • change in Cholesterol, Triglyceride [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • change in HOMA-IR [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • change in BMI [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  • changes in NAS [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
    Subjects with liver biopsy:


Enrollment: 60
Study Start Date: May 2011
Study Completion Date: October 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
30mig/bid or 60mg/bid P.O
Experimental: Oltipraz Drug: Oltipraz
30mig/bid or 60mg/bid P.O

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01373554

Locations
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
PharmaKing
Investigators
Principal Investigator: YoonJun Kim, MD.PhD Seoul National University Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: PharmaKing
ClinicalTrials.gov Identifier: NCT01373554     History of Changes
Other Study ID Numbers: PMK-N01GI1
Study First Received: June 3, 2011
Last Updated: December 8, 2013
Health Authority: Korea: Food and Drug Administration

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Oltipraz
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Schistosomicides
Antiplatyhelmintic Agents
Anthelmintics
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

ClinicalTrials.gov processed this record on August 18, 2014