Genetic Effect on Omega 3 Fatty Acids for the Treatment of Fatty Liver Disease
To explore whether there is a different response to the omega-3 fatty acid supplementation vs omega-3 fatty acid rich diet with respect to the hepatic fat fraction % (HFF), triglyceride, and ALT levels between the rs738409 minor allele (GG) and the common allele homozygous (CC) of PNPLA3.
Hypothesis: We expect that subjects homozygous for the minor allele of the rs73049 SNP will lower their triglyceride, hepatic fat content, and ALT levels more with either intervention than the common allele homozygous supplementation. Moreover, it is hypothesized the group under omega 3 fatty acid (n-3) supplement will have greater improvements over the diet group.
Non Alcoholic Fatty Liver Disease
Alanine Aminotransferase, Plasma Level of, Quantitative Trait Locus 1
Dietary Supplement: Lovaza
Other: Omega diet
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||The Genetic Effect on Omega 3 Fatty Acid Supplementation for the Treatment of Non Alcoholic Fatty Liver Disease in Obese Children and Adolescents|
- reduction in hepatic fat fraction [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||March 2012|
|Estimated Study Completion Date:||March 2018|
|Estimated Primary Completion Date:||March 2018 (Final data collection date for primary outcome measure)|
We expect that subjects homozygous for the minor allele of the rs73049 SNP will lower their triglyceride, hepatic fat content, and ALT levels more with lovaza intervention (4 grams/day for 12 weeks) than the common allele homozygous supplementation. Subjects will have study visits every week during study period to assess compliance and adverse events.
Dietary Supplement: Lovaza
eligible subjects will receive 4 grams/day of lovaza (pills)for 12 weeks. Subjects will attend weekly visits to measure compliance, draw serum samples and replenish supplement supply.
Other Name: omega 3 ethyl ester
Active Comparator: omega diet
We expect that subjects homozygous for the minor allele of the rs73049 SNP will lower their triglyceride, hepatic fat content, and ALT levels more with omega diet intervention than the common allele homozygous supplementation. Subjects entering the diet arm of the intervention will be provided food by the researchers for 12 weeks. (Meal plan provided in Appendix A.) The meal plan is an ω6/ω3 ratio will range between 4:1 to 3:1. Each subject will be instructed by an RD monthly to assist with adherence. Subjects will meet with the RD, or other study personnel, every 3-4 days for replenishment of food, anthropometric measurements, and compliance concerns.
Other: Omega diet
eligible subjects will receive omega rich diet for 12 weeks with weekly appointments to obtain food records, draw serum samples and provide meals.
Nonalcoholic fatty liver disease (NAFLD) is emerging as one of the most common complications of childhood obesity. It is associated with and predicts the metabolic syndrome, independent of overall obesity. Increased ALT levels are associated with deterioration in insulin sensitivity and glucose tolerance, as well as with increasing free fatty acid (FFA) and triglyceride levels. The prevalence of metabolic syndrome and prediabetes increases with the increases in hepatic fat content in a cohort of obese adolescents.
Fatty liver, independent of visceral and intramyocellular lipid content plays a central role in the impairment of liver, muscle and adipose insulin sensitivity in obese adolescents. Thus, fatty liver disease may be the hepatic component of the metabolic syndrome.
Omega 3 fatty acids lower plasma triglyceride concentrations. Doses between 3-4grams of fish oil are required for significant triglyceride lowering effects. This requires the use of commercially available concentrates of omega 3 fatty acids such as Lovaza which are effective as 4 capsules per day compared to 14 capsules per day of ordinary omega 3 fatty acids.
Lovaza arm subjects will receive 4mg/day of the dietary supplement for 12 weeks.
The subjects entering the diet arm of the study will be consuming an omega rich diet that is tailored to their caloric needs. This calculation is based on the patient's weight, age, and gender with the purpose of not modifying their weight at all. Weight maintenance is a very important factor in this arm of the study. They will be on the diet for 12 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01556113
|Contact: Bridget Pierpont, M.A.||firstname.lastname@example.org|
|United States, Connecticut|
|Yale School of Medicine||Recruiting|
|New Haven, Connecticut, United States, 06510|
|Contact: Bridget Pierpont, M.A. 203-785-2942 email@example.com|
|Contact: Grace Kim, M.D. firstname.lastname@example.org|
|Principal Investigator: Grace Kim, M.A./M.D.|
|Principal Investigator:||Grace Kim, M.D.||Yale University, attending|
|Principal Investigator:||Nicola Santoro, MD/PhD||Yale University|