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

NCT01373554 | Completed Phase 2 DMC

• 1 other identifier: PMK-N01GI1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 5

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.

Conditions

Non-alcoholic Fatty Liver Disease

Outcome Measures

Primary Outcomes (1)

• MRS

  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

  24 weeks

Secondary Outcomes (5)

• change in ALT, AST and total bilirubin

  24 weeks

• change in Cholesterol, Triglyceride

  24 weeks

• change in HOMA-IR

  24 weeks

• change in BMI

  24 weeks

• changes in NAS

  24 weeks

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Oltipraz

EXPERIMENTAL

Drug: Oltipraz

Interventions

Placebo DRUG

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

Placebo

Oltipraz DRUG

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

Oltipraz

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients over 18, under 75 years of age
• Patients with non-alcoholic fatty liver disease

You may not qualify if:

• 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

Sponsors & Collaborators

• PharmaKing: lead

Study Sites (5)

Inje University Ilsan Paik Hospital

Dahwa-dong, Ilsanseo-gu, Goyang-si, Gyeonggi-do, 411-706, South Korea

Location

NHUS Ilsan Hospital

Ilsan-ro Ilsan-donggu, Goyang-si, 410-719, South Korea

Location

Seoul National University Hospital

Daehak-ro Jongno-gu, Seoul, 110-744, South Korea

Location

Korea University Guro hospital

Gurodong-ro, Seoul, 152-703, South Korea

Location

Boramae Hospital

Sindaebang-dong Dongjak-gu, Seoul, 156-707, South Korea

Location

Related Publications (2)

• 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.

  PMID: 20664537 BACKGROUND

• 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.

  PMID: 28225186 DERIVED

Related Links

• Oltipraz

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease

Interventions

oltipraz

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases

Study Officials

• YoonJun Kim, MD.PhD

  Seoul National University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2011
• First Posted: June 15, 2011
• Study Start: May 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: October 1, 2013
• Last Updated: December 10, 2013

Record last verified: 2013-12

Locations

KR (5)