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

NCT ID: NCT01094158

Last Updated: 2012-01-31

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2010-11-30

Study Completion Date

2012-01-31

Brief Summary

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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

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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.

Conditions

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Non-Alcoholic Fatty Liver Disease Nonalcoholic Steatohepatitis Metabolic Syndrome

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Caregivers Investigators

Study Groups

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high dose

Aramchol 300 mg daily (high dose)

Group Type EXPERIMENTAL

Aramchol

Intervention Type DRUG

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

low dose

100 mg daily (low dose)

Group Type EXPERIMENTAL

Aramchol

Intervention Type DRUG

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

Placebo

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

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

tablets packaged in bottles given orally once a day in the morning within approximately 10 minutes after breakfast

Interventions

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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

Intervention Type DRUG

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

Intervention Type DRUG

Placebo

tablets packaged in bottles given orally once a day in the morning within approximately 10 minutes after breakfast

Intervention Type DRUG

Other Intervention Names

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Arachidyl amido cholanoic acid Arachidyl amido cholanoic acid

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Tel-Aviv Sourasky Medical Center

OTHER_GOV

Sponsor Role collaborator

Beilinson Hospital, Petach Tikva,Israel

UNKNOWN

Sponsor Role collaborator

Meir Medical Center

OTHER

Sponsor Role collaborator

Kaplan Hospital ,Rehovot,Israel

UNKNOWN

Sponsor Role collaborator

Soroka Hospital,Beer Sheva,Israel

UNKNOWN

Sponsor Role collaborator

Hadassah Medical Organization

OTHER

Sponsor Role collaborator

Hillel Yaffe Medical Center

OTHER_GOV

Sponsor Role collaborator

Rambam Hospital, Haifa, Israel

UNKNOWN

Sponsor Role collaborator

The Lady Davis Carmel Medical Center

UNKNOWN

Sponsor Role collaborator

Holy Family Hospital, Nazareth, Israel

OTHER

Sponsor Role collaborator

Ziv Hospital

OTHER_GOV

Sponsor Role collaborator

Galmed Medical Reserch

INDUSTRY

Sponsor Role lead

Responsible Party

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Liver unit, Department of Gastroenterology and Hepatology, Sourasky Medical Center. Tel Aviv.

Principal Investigators

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Ran Oren, Doctor

Role: PRINCIPAL_INVESTIGATOR

Liver & Gastroenterology Department,The Tel Aviv Sourasky Medical Center

Locations

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Soroka Medical Center

Beersheba, , Israel

Site Status

Hillel Yaffe Medical Center

Hadera, , Israel

Site Status

Rambam

Haifa, , Israel

Site Status

The Lady Davis Carmel Medical Center

Haifa, , Israel

Site Status

Hadassah Ein Kerem M.C

Jerusalem, , Israel

Site Status

Meir Medical Center

Kfar Saba, , Israel

Site Status

Holy Family HOSPITAL

Nazareth, , Israel

Site Status

Belinson,Rabin Medical Center

Petah Tikva, , Israel

Site Status

Kaplan M.C

Rehovot, , Israel

Site Status

Safed Ziv Hospital

Safed, , Israel

Site Status

The Tel Aviv Sourasky Medical Center

Tel Aviv, , Israel

Site Status

Countries

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Israel

References

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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.

Reference Type BACKGROUND
PMID: 18989145 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 12883488 (View on PubMed)

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.

Reference Type DERIVED
PMID: 24815326 (View on PubMed)

Other Identifiers

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Aramchol NAFLD Phase-II

Identifier Type: -

Identifier Source: org_study_id

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