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

Non-alcoholic Fatty Liver Disease Clinical Trial

— PMK-N01GI1  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01373554
• Other study ID #: PMK-N01GI1
• Status: Completed
• Phase: Phase 2
• First received: June 3, 2011
• Last updated: December 8, 2013
• Start date: May 2011
• Est. completion date: October 2013

Study information

• Verified date: December 2013
• Source: PharmaKing
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: October 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease

Intervention

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

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Hospital	Daehak-ro Jongno-gu	Seoul
Korea, Republic of	Inje University Ilsan Paik Hospital	Dahwa-dong, Ilsanseo-gu	Goyang-si, Gyeonggi-do
Korea, Republic of	Korea University Guro hospital	Gurodong-ro	Seoul
Korea, Republic of	NHUS Ilsan Hospital	Ilsan-ro Ilsan-donggu	Goyang-si
Korea, Republic of	Boramae Hospital	Sindaebang-dong Dongjak-gu	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
PharmaKing

Country where clinical trial is conducted

Korea, Republic of, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	change in ALT, AST and total bilirubin		24 weeks	No
Secondary	change in Cholesterol, Triglyceride		24 weeks	No
Secondary	change in HOMA-IR		24 weeks	No
Secondary	change in BMI		24 weeks	No
Secondary	changes in NAS	Subjects with liver biopsy:	24 weeks	No

External Links

•   Oltipraz