Trial record 3 of 151 for:    Non-Alcoholic Steatohepatitis

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

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2014 by University Health Network, Toronto
Sponsor:
Collaborators:
Canadian Institutes of Health Research (CIHR)
American College of Gastroenterology
Information provided by (Responsible Party):
Johane Allard, University Health Network, Toronto
ClinicalTrials.gov Identifier:
NCT01056133
First received: January 22, 2010
Last updated: May 23, 2014
Last verified: May 2014
  Purpose

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 Intervention Phase
Non-alcoholic Fatty Liver Disease
Non-alcoholic Steatohepatitis
Other: Omega-3 capsules-Fish Oil
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University Health Network, Toronto:

Primary Outcome Measures:
  • Liver histology [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    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:
  • Plasma and RBC fatty acid composition and PC:PE ratio [ Time Frame: At 3,6,12 months ] [ Designated as safety issue: Yes ]
  • Blood biochemistry (blood sugar control, lipid profile, liver enzymes) [ Time Frame: Baseline, 6, 12 months ] [ Designated as safety issue: Yes ]
  • Intestinal microbiota [ Time Frame: Baseline, 6, 12 months ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • Plasma free choline [ Time Frame: Baseline, 6, 12 months ] [ Designated as safety issue: No ]
  • Bacterial DNA in plasma [ Time Frame: Baseline, 6, 12 months ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Environmental questionnaire [ Time Frame: Baseline, 6, 12 months ] [ Designated as safety issue: No ]
    To assess factors that influence intestinal microbiota


Estimated Enrollment: 40
Study Start Date: October 2009
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01056133

Contacts
Contact: Bianca M Arendt, Ph D 416-340-4104 barendt@uhnresearch.ca
Contact: Hannah R Da Silva, RD 416-340-4104 hdasilva@uhnresearch.ca

Locations
Canada, Ontario
University Health Network, Toronto General Hospital Recruiting
Toronto, Ontario, Canada, M5G 1Z5
Contact: Bianca M Arendt, PhD    416-340-4104    barendt@uhnresearch.ca   
Principal Investigator: Johane P Allard, MD, FRCPC         
Sponsors and Collaborators
Johane Allard
Canadian Institutes of Health Research (CIHR)
American College of Gastroenterology
Investigators
Principal Investigator: Johane P Allard, MD, FRCPC University Health Network, Toronto
  More Information

No publications provided

Responsible Party: Johane Allard, Professor, Gastroenterologist, University Health Network, Toronto
ClinicalTrials.gov Identifier: NCT01056133     History of Changes
Other Study ID Numbers: 08-0874-A, CIHR Grant#89705, MOP-123459
Study First Received: January 22, 2010
Last Updated: May 23, 2014
Health Authority: Canada: Health Canada

Keywords provided by University Health Network, Toronto:
non-alcoholic fatty liver disease
non-alcoholic steatohepatitis

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on July 26, 2014