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Study of Aramchol in Patients With Fatty Liver Disease or Nonalcoholic Steatohepatitis (Aramchol003)

Primary Purpose

Non-Alcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, Metabolic Syndrome

Status
Completed
Phase
Phase 2
Locations
Israel
Study Type
Interventional
Intervention
Aramchol
Aramchol
Placebo
Sponsored by
Galmed Medical Reserch
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Alcoholic Fatty Liver Disease focused on measuring NAFLD, NASH, Fatty Liver, Metabolic Syndrome, Endothelial Dysfunction, Insulin Resistance, Liver Fat

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Soroka Medical Center
  • Hillel Yaffe Medical Center
  • Rambam
  • The Lady Davis Carmel Medical Center
  • Hadassah Ein Kerem M.C
  • Meir Medical Center
  • Holy Family HOSPITAL
  • Belinson,Rabin Medical Center
  • Kaplan M.C
  • Safed Ziv Hospital
  • The Tel Aviv Sourasky Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

high dose

low dose

Placebo

Arm Description

Aramchol 300 mg daily (high dose)

100 mg daily (low dose)

Placebo and two doses will be compared. The Aramchol: placebo ratio is of 2:1.

Outcomes

Primary Outcome Measures

The difference between initial and final liver triglyceride concentration (measured by NMRS) comparing the Aramchol and placebo treated patients.

Secondary Outcome Measures

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

Full Information

First Posted
February 17, 2010
Last Updated
January 30, 2012
Sponsor
Galmed Medical Reserch
Collaborators
Tel-Aviv Sourasky Medical Center, Beilinson Hospital, Petach Tikva,Israel, Meir Medical Center, Kaplan Hospital ,Rehovot,Israel, Soroka Hospital,Beer Sheva,Israel, Hadassah Medical Organization, Hillel Yaffe Medical Center, Rambam Hospital, Haifa, Israel, The Lady Davis Carmel Medical Center, Holy Family Hospital, Nazareth, Israel, Ziv Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT01094158
Brief Title
Study of Aramchol in Patients With Fatty Liver Disease or Nonalcoholic Steatohepatitis
Acronym
Aramchol003
Official Title
A Phase II Placebo Controlled Randomised Study of Aramchol on Liver Triglyceride in Patients With Steatosis Due to NAFLD or NASH
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Completed
Study Start Date
November 2010 (undefined)
Primary Completion Date
November 2011 (Actual)
Study Completion Date
January 2012 (Actual)

3. Sponsor/Collaborators

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

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Alcoholic Fatty Liver Disease, Nonalcoholic Steatohepatitis, Metabolic Syndrome
Keywords
NAFLD, NASH, Fatty Liver, Metabolic Syndrome, Endothelial Dysfunction, Insulin Resistance, Liver Fat

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
high dose
Arm Type
Experimental
Arm Description
Aramchol 300 mg daily (high dose)
Arm Title
low dose
Arm Type
Experimental
Arm Description
100 mg daily (low dose)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo and two doses will be compared. The Aramchol: placebo ratio is of 2:1.
Intervention Type
Drug
Intervention Name(s)
Aramchol
Other Intervention Name(s)
Arachidyl amido cholanoic acid
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Aramchol
Other Intervention Name(s)
Arachidyl amido cholanoic acid
Intervention Description
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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
tablets packaged in bottles given orally once a day in the morning within approximately 10 minutes after breakfast
Primary Outcome Measure Information:
Title
The difference between initial and final liver triglyceride concentration (measured by NMRS) comparing the Aramchol and placebo treated patients.
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Comparing secondary variables of liver, metabolic and endothelial functions between the Aramchol and the placebo arms.
Description
Comparing liver enzymes, markers of endothelial dysfunction, insulin resistance, SCD1 activity and cholesterol synthesis and lipid levels, between the Aramchol and the placebo arms
Time Frame
3 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ran Oren, Doctor
Organizational Affiliation
Liver & Gastroenterology Department,The Tel Aviv Sourasky Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Soroka Medical Center
City
Beer Sheva
ZIP/Postal Code
84101
Country
Israel
Facility Name
Hillel Yaffe Medical Center
City
Hadera
ZIP/Postal Code
38100
Country
Israel
Facility Name
Rambam
City
Haifa
ZIP/Postal Code
31096
Country
Israel
Facility Name
The Lady Davis Carmel Medical Center
City
Haifa
ZIP/Postal Code
34362
Country
Israel
Facility Name
Hadassah Ein Kerem M.C
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Meir Medical Center
City
Kfar Saba
ZIP/Postal Code
44281
Country
Israel
Facility Name
Holy Family HOSPITAL
City
Nazareth
Country
Israel
Facility Name
Belinson,Rabin Medical Center
City
Petah Tikva
ZIP/Postal Code
49100
Country
Israel
Facility Name
Kaplan M.C
City
Rehovot
ZIP/Postal Code
76100
Country
Israel
Facility Name
Safed Ziv Hospital
City
Safed
ZIP/Postal Code
13100
Country
Israel
Facility Name
The Tel Aviv Sourasky Medical Center
City
Tel Aviv
ZIP/Postal Code
64239
Country
Israel

12. IPD Sharing Statement

Citations:
PubMed Identifier
18989145
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.
Results Reference
background
PubMed Identifier
12883488
Citation
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. doi: 10.1053/jhep.2003.50348.
Results Reference
background
PubMed Identifier
24815326
Citation
Safadi R, Konikoff FM, Mahamid M, Zelber-Sagi S, Halpern M, Gilat T, Oren R; FLORA Group. The fatty acid-bile acid conjugate Aramchol reduces liver fat content in patients with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. 2014 Dec;12(12):2085-91.e1. doi: 10.1016/j.cgh.2014.04.038. Epub 2014 May 9.
Results Reference
derived

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

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