Effect of Fish-oil on Non-alcoholic Steatohepatitis (NASH)
|Non-alcoholic Fatty Liver Disease Non-alcoholic Steatohepatitis||Other: Omega-3 capsules-Fish Oil||Phase 2|
|Study Design:||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)|
- 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)
- 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 ]
- Environmental questionnaire [ Time Frame: Baseline, 6, 12 months ]To assess factors that influence intestinal microbiota
|Study Start Date:||October 2009|
|Study Completion Date:||August 2015|
|Primary Completion Date:||January 2015 (Final data collection date for primary outcome measure)|
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01056133
|University Health Network, Toronto General Hospital|
|Toronto, Ontario, Canada, M5G 1Z5|
|Principal Investigator:||Johane P Allard, MD, FRCPC||University Health Network, Toronto|