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Effect of Fish-oil on Non-alcoholic Steatohepatitis (NASH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01056133
Recruitment Status : Completed
First Posted : January 26, 2010
Last Update Posted : May 12, 2016
Canadian Institutes of Health Research (CIHR)
American College of Gastroenterology
Information provided by (Responsible Party):
Johane Allard, University Health Network, Toronto

Brief Summary:
The purpose of this study is to determine the effect of Omega-3 Fish oil supplementation on hepatic gene expression in patients with Non Alcoholic Steatohepatitis (NASH). In addition, effects of fish oil on intestinal microbiota will be assessed.

Condition or disease Intervention/treatment Phase
Non-alcoholic Fatty Liver Disease Non-alcoholic Steatohepatitis Other: Omega-3 capsules-Fish Oil Phase 2

Detailed Description:

Changes in fatty acid (FA) composition within the liver may influence lipid metabolism and inflammation. This is poorly understood in humans.

Especially omega-3 FA are important: They promote FA oxidation over storage and are important for export of lipids from the liver. Omega-3 FA have also anti-inflammatory properties.

Changes in liver FA composition may be influenced by dietary intake, high rate of lipid peroxidation (LP) or low delta-6 desaturase enzyme activity. We and others recently showed that NASH patients had lower hepatic n-3 and n-6 polyunsaturated FA (PUFA) with increased lipid peroxidation and low antioxidant status when compared to patients with minimal findings on liver biopsy. The dietary intake of FA was similar among the 3 groups suggesting that the difference in hepatic FA composition may be related to high lipid peroxidation or low delta-6 desaturase activity. This difference in hepatic FA composition may be of significance in the pathogenesis of NASH since it may change gene expressions in regard to lipid metabolism.

This pilot study in NASH to assess the effect of n-3 PUFA supplementation on FA composition (liver and red blood cells), hepatic gene expression, and histology. We will also assess the ratio of phosphatidylcholine (PC) to phosphatidylethanolamine (PE) in liver and red blood cells (RBC). Oxidative stress, insulin resistance and nutritional measurements will be performed to further characterize these patients.

New research suggests that the composition of the gut flora (intestinal microbiota) may play a role in the development of NASH. The effect of fish oil on the intestinal microbiota has not been examined in humans. Therefore, intestinal microbiota is also measured before and after intervention and associations between changes in microbiota and changes in liver histology will be examined. In addition, bacterial products (short chain fatty acids in stool, lipopolysaccharide in plasma, bacterial DNA in plasma), and plasma choline will be measured. An environmental questionnaire will capture factors that can influence the intestinal microbiota.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 20 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Pilot Study to Determine the Effect of Omega-3 Polyunsaturated Fatty Acids From Fish Oil on Patients With Non-Alcoholic Steatohepatitis (NASH)
Study Start Date : October 2009
Actual Primary Completion Date : January 2015
Actual Study Completion Date : August 2015

Arm Intervention/treatment
Experimental: Omega-3 capsules-Fish Oil
Omega-3 fatty acids in the form of fish oil capsules (2g/d)
Other: Omega-3 capsules-Fish Oil
Patients will take 2 capsules (1.0 g each) of n-3 PUFA (0.82/0.44 g of EPA/DHA) daily x 12 months. Since n-3 PUFA supplementation can be a potential treatment for NASH and since BMI will be< 30 kg/m2 for all subjects, patients will be told to keep their lifestyle, diet and medication stable (unless medically necessary) for the study duration in order to minimize environmental effect on gene expression.
Other Names:
  • Product Name: Amber 40/20 Ethyl ester (EE)
  • 1000 mg capsules (lemon-lime flavor)
  • Product Code: 4020PB1000CT

Primary Outcome Measures :
  1. Liver histology [ Time Frame: Baseline, 12 months ]
    Liver histology will be assessed for diagnosis of NASH (steatosis, inflammation, ballooning, fibrosis, mallory bodies, Non-alcoholic fatty liver disease activity score (NAS)

Secondary Outcome Measures :
  1. Plasma and RBC fatty acid composition and PC:PE ratio [ Time Frame: At 3,6,12 months ]
  2. Blood biochemistry (blood sugar control, lipid profile, liver enzymes) [ Time Frame: Baseline, 6, 12 months ]
  3. Intestinal microbiota [ Time Frame: Baseline, 6, 12 months ]
    Composition of intestinal microbiota will be measured in stool samples using Ion Torrent technology and quantitative reverse transcription polymerase chain reaction

  4. Plasma endotoxin [ Time Frame: Baseline, 6, 12 months ]
  5. Plasma free choline [ Time Frame: Baseline, 6, 12 months ]
  6. Bacterial DNA in plasma [ Time Frame: Baseline, 6, 12 months ]

Other Outcome Measures:
  1. Environmental questionnaire [ Time Frame: Baseline, 6, 12 months ]
    To assess factors that influence intestinal microbiota

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with biopsy-proven NASH; male and female; age 18-65 years; BMI ≤ 40 kg/m2, alcohol consumption <20g/d; non-smokers; if known to have hyperlipidemia or diabetes, need to be stable drug regimen.

Exclusion Criteria:

  • Liver disease of other etiology; documented HIV infection, anticipated need for liver transplantation in one year or complications such as recurrent variceal bleeding, spontaneous portosystemic encephalopathy, ascites or jaundice; concurrent medical illnesses, abnormal coagulation or other reasons judged by the hepatologist to contraindicate a liver biopsy; chronic gastrointestinal diseases, previous gastrointestinal surgery modifying the anatomy, patients with diabetes requiring insulin; medications known to precipitate steatohepatitis in the 6 months prior to entry; regular intake of non-steroidal anti-inflammatory drugs, regular intake of antioxidant vitamin or omega-3/fish oil supplements, prebiotics, probiotics, antibiotics, or laxatives; ursodeoxycholic acid or any experimental drug in the 6 months prior to study entry; smokers; pregnancy or lactating; female subjects who are not surgically sterile or postmenopausal and who are not using medically acceptable methods of birth control during the trial and for 30 days after the treatment period.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01056133

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Canada, Ontario
University Health Network, Toronto General Hospital
Toronto, Ontario, Canada, M5G 1Z5
Sponsors and Collaborators
Johane Allard
Canadian Institutes of Health Research (CIHR)
American College of Gastroenterology
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Principal Investigator: Johane P Allard, MD, FRCPC University Health Network, Toronto
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Responsible Party: Johane Allard, Professor, Gastroenterologist, University Health Network, Toronto Identifier: NCT01056133    
Other Study ID Numbers: 08-0874-A
CIHR Grant#89705 ( Other Grant/Funding Number: Canadian Institutes of Health Research )
MOP-123459 ( Other Grant/Funding Number: Canadian Institutes of Health Research )
First Posted: January 26, 2010    Key Record Dates
Last Update Posted: May 12, 2016
Last Verified: May 2016
Keywords provided by Johane Allard, University Health Network, Toronto:
non-alcoholic fatty liver disease
non-alcoholic steatohepatitis
Additional relevant MeSH terms:
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Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases