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

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ClinicalTrials.gov Identifier: NCT01056133
Recruitment Status : Completed
First Posted : January 26, 2010
Last Update Posted : May 12, 2016
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
American College of Gastroenterology
Information provided by (Responsible Party):
Johane Allard, University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE January 22, 2010
First Posted Date  ICMJE January 26, 2010
Last Update Posted Date May 12, 2016
Study Start Date  ICMJE October 2009
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 17, 2013)
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)
Original Primary Outcome Measures  ICMJE
 (submitted: January 25, 2010)
In NASH patients who consent to take Omega-3 over 12 months and have a second liver biopsy, the effect of Omega-3 supplementation on gene expression(main variable) will be assessed along with fatty acid composition, oxidative stress and histology [ Time Frame: At 12 months ]
Change History Complete list of historical versions of study NCT01056133 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 23, 2014)
  • Plasma and RBC fatty acid composition and PC:PE ratio [ Time Frame: At 3,6,12 months ]
  • Blood biochemistry (blood sugar control, lipid profile, liver enzymes) [ Time Frame: Baseline, 6, 12 months ]
  • 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
  • Plasma endotoxin [ Time Frame: Baseline, 6, 12 months ]
  • Plasma free choline [ Time Frame: Baseline, 6, 12 months ]
  • Bacterial DNA in plasma [ Time Frame: Baseline, 6, 12 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 25, 2010)
  • Plasma and RBC fatty acid composition and PC:PE ratio [ Time Frame: At 3,6,12 months ]
  • Blood biochemistry (blood sugar control, lipid profile, liver enzymes) [ Time Frame: At 3,6,12 months ]
Current Other Pre-specified Outcome Measures
 (submitted: July 17, 2013)
Environmental questionnaire [ Time Frame: Baseline, 6, 12 months ]
To assess factors that influence intestinal microbiota
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Effect of Fish-oil on Non-alcoholic Steatohepatitis (NASH)
Official Title  ICMJE A Pilot Study to Determine the Effect of Omega-3 Polyunsaturated Fatty Acids From Fish Oil on Patients With Non-Alcoholic Steatohepatitis (NASH)
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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Non-alcoholic Fatty Liver Disease
  • Non-alcoholic Steatohepatitis
Intervention  ICMJE 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
Study Arms  ICMJE Experimental: Omega-3 capsules-Fish Oil
Omega-3 fatty acids in the form of fish oil capsules (2g/d)
Intervention: Other: Omega-3 capsules-Fish Oil
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 10, 2016)
20
Original Estimated Enrollment  ICMJE
 (submitted: January 25, 2010)
40
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date January 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01056133
Other Study ID Numbers  ICMJE 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 )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Johane Allard, University Health Network, Toronto
Study Sponsor  ICMJE Johane Allard
Collaborators  ICMJE
  • Canadian Institutes of Health Research (CIHR)
  • American College of Gastroenterology
Investigators  ICMJE
Principal Investigator: Johane P Allard, MD, FRCPC University Health Network, Toronto
PRS Account University Health Network, Toronto
Verification Date May 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP