Study of Aramchol in Patients With Fatty Liver Disease or Nonalcoholic Steatohepatitis

Metabolic Syndrome Clinical Trial

— Aramchol003  

Official title:

A Phase II Placebo Controlled Randomised Study of Aramchol on Liver Triglyceride in Patients With Steatosis Due to NAFLD or NASH

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01094158
• Other study ID #: Aramchol NAFLD Phase-II
• Status: Completed
• Phase: Phase 2
• First received: February 17, 2010
• Last updated: January 30, 2012
• Start date: November 2010
• Est. completion date: January 2012

Study information

• Verified date: January 2012
• Source: Galmed Medical Reserch
• Contact: n/a
• Is FDA regulated: No
• Health authority: Israel: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

Primary purpose: Compare the changes in liver triglycerides concentration in the Aramchol versus the placebo arm following three month treatment.

Secondary purpose: Comparing liver enzymes, markers of endothelial dysfunction, insulin resistance, SCD1 activity and cholesterol synthesis and lipid levels, between the Aramchol and the placebo arms.

Description:

A Phase II, multicenter, double blind, randomized, placebo controlled study on the effect of Aramchol on liver triglycerides concentration in patients with steatosis due to NAFLD or NASH

The purpose of the study is to test whether Aramchol will reduce safely and effectively liver fat concentration in patients with NAFLD and NASH.

Aramchol inhibits the liver enzyme Stearoyl Coenzyme A Desaturase (SCD). It reduces fatty acid synthesis while increasing fatty acid oxidation. It was shown to reduce liver fat in animal models with diet induced Fatty Liver. It has also marked hypocholesterolemic effects, mainly via upregulation of theABCA1 cholesterol transporter. It thus causes(incomplete) SCD inhibition while being antiatherogenic

Primary purpose: Compare the changes in liver triglycerides concentration in the Aramchol versus the placebo arm following three month treatment.

Secondary purpose: Comparing liver enzymes, markers of endothelial dysfunction, insulin resistance, SCD1 activity and cholesterol synthesis and lipid levels, between the Aramchol and the placebo arms.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: January 2012
• Est. primary completion date: November 2011
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Patients with histologically proven NAFLD or NASH based on a biopsy performed during the preceding 18 months fulfilling the following criteria:

• At least 15% of hepatocytes showing steatosis,with Fibrosis of not more than stage 3, with at most bridging fibrosis.

Patients with a NAFLD activity score 0-2 will be considered to have NAFLD. Biopsies with an activity score of 3 or more will be considered NASH.

• Triglycerides concentration in the liver of 6% or more as measured by NMRS.

• At least two elevated serum ALT levels in the previous six months, with latest test within 2 months of trial.

• Normal or only slightly impaired synthetic liver function (serum albumin >3.5gm%, INR 0.8-1.3)

• Male or female aged 18-75 years.

• Negative pregnancy test at study entry for females of child bearing potential.

• Females of child bearing potential practicing reliable contraception throughout the study period.

• Signature of the written informed consent

Exclusion Criteria:

• Evidence of cirrhosis on liver biopsy.

• Evidence of fibrosis of more than stage 3 on liver biopsy.

• Patient with liver disease due to acute or chronic hepatitis A, B,C, HIV, and all other liver diseases affecting liver function. Patients with cysts, hemangiomas, or similar abnormalities, are accepted.

• BMI > 35 or >130 kg body weight

• Any other concomitant, significant: metabolic, infectious, inflammatory, neoplastic, or other non-liver disease.

• Various concomitant diseases requiring chronic steroid administration.

• Use of warfarin, metformin, thiaglitazones, insulin or current steroid therapy of more than 3 days.

• Use of other investigational agents < 30 days prior to the study.

• Pregnancy

• Daily alcohol intake > 10gm/day.

• Patients with symptoms of significant mental illness. Inability to cooperate or communicate with the investigator, who are unlikely to comply with the study requirements, or who are unable to give informed consent.

• Performance status: WHO performance status =4.

Study Design

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

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Metabolic Syndrome
• Metabolic Syndrome X
• Non-Alcoholic Fatty Liver Disease
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• Aramchol
100mg/d tablets packaged in bottles given orally once a day in the morning within 10 minutes after breakfast for a total period time of 3 months
• Aramchol
300 mg/d tablets packaged in bottles given orally once a day in the morning within 10 minutes after breakfast for a total period time of 3 months
• Placebo
tablets packaged in bottles given orally once a day in the morning within approximately 10 minutes after breakfast

Locations

Country	Name	City	State
Israel	Soroka Medical Center	Beer Sheva
Israel	Hillel Yaffe Medical Center	Hadera
Israel	Rambam	Haifa
Israel	The Lady Davis Carmel Medical Center	Haifa
Israel	Hadassah Ein Kerem M.C	Jerusalem
Israel	Meir Medical Center	Kfar Saba
Israel	Holy Family HOSPITAL	Nazareth
Israel	Belinson,Rabin Medical Center	Petah Tikva
Israel	Kaplan M.C	Rehovot
Israel	Safed Ziv Hospital	Safed
Israel	The Tel Aviv Sourasky Medical Center	Tel Aviv

Sponsors (12)

Lead Sponsor	Collaborator
Galmed Medical Reserch	Beilinson Hospital, Petach Tikva,Israel, Hadassah Medical Organization, Hillel Yaffe Medical Center, Holy Family Hospital, Nazareth, Israel, Kaplan Hospital ,Rehovot,Israel, Meir Medical Center, Rambam Hospital, Haifa, Israel, Soroka Hospital,Beer Sheva,Israel, Tel-Aviv Sourasky Medical Center, The Lady Davis Carmel Medical Center, Ziv Hospital

Country where clinical trial is conducted

Israel, 

References & Publications (2)

Gilat T, Leikin-Frenkel A, Goldiner I, Juhel C, Lafont H, Gobbi D, Konikoff FM. Prevention of diet-induced fatty liver in experimental animals by the oral administration of a fatty acid bile acid conjugate (FABAC). Hepatology. 2003 Aug;38(2):436-42. — View Citation

Leikin-Frenkel A, Goldiner I, Leikin-Gobbi D, Rosenberg R, Bonen H, Litvak A, Bernheim J, Konikoff FM, Gilat T. Treatment of preestablished diet-induced fatty liver by oral fatty acid-bile acid conjugates in rodents. Eur J Gastroenterol Hepatol. 2008 Dec;20(12):1205-13. doi: 10.1097/MEG.0b013e3282fc9743. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The difference between initial and final liver triglyceride concentration (measured by NMRS) comparing the Aramchol and placebo treated patients.		3 months	Yes
Secondary	Comparing secondary variables of liver, metabolic and endothelial functions between the Aramchol and the placebo arms.	Comparing liver enzymes, markers of endothelial dysfunction, insulin resistance, SCD1 activity and cholesterol synthesis and lipid levels, between the Aramchol and the placebo arms	3 months	Yes