Genetic Effect on Omega 3 Fatty Acids for the Treatment of Fatty Liver Disease

Sponsor

Yale University (Other)

Overall Status

Completed

CT.gov ID

NCT01556113

Collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

Enrollment

Location

Arms

59.1

Actual Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

To explore whether there is a different response to 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 dietary intervention than the common allele homozygous supplementation.

Condition or Disease	Intervention/Treatment	Phase
Non Alcoholic Fatty Liver Disease Steatohepatitis Hypertriglyceridemia Alanine Aminotransferase, Plasma Level of, Quantitative Trait Locus 1	Other: Omega diet	N/A

Detailed Description

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. The subjects entering the omega diet 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.

Study Design

Study Type:

Interventional

Actual Enrollment :

17 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (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

Actual Study Start Date :

Mar 1, 2012

Actual Primary Completion Date :

Feb 1, 2017

Actual Study Completion Date :

Feb 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: omega diet carrying CC/CG genotype Subjects homozygous for the major allele of the rs73049 SNP or heterozygous (CC and CG)	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.
Active Comparator: omega diet carrying GG genotype Subjects homozygous for the minor allele of the rs73049 SNP (GG)	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.

Arm

Intervention/Treatment

Active Comparator: omega diet carrying CC/CG genotype

Subjects homozygous for the major allele of the rs73049 SNP or heterozygous (CC and CG)

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.

Active Comparator: omega diet carrying GG genotype

Subjects homozygous for the minor allele of the rs73049 SNP (GG)

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.

Outcome Measures

Primary Outcome Measures

reduction in hepatic fat fraction [12 weeks]
subjects follow study designed meal plan

Secondary Outcome Measures

reduction in triglycerides [12 weeks]
subjects follow study designed meal plan
lower ALT levels [12 weeks]
subjects follow study designed meal plan

Eligibility Criteria

Criteria

Ages Eligible for Study:

10 Years to 19 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

10 to 19 years of age
BMI equal or greater than the 95th percentile for age and gender
Genotype PNPLA3 CC or GG
Liver MRI Hepatic Fat fraction ≥5.5%

Exclusion Criteria:

Food allergy to fish or any components of the pills which include alpha tocopherol partially hydrogenated vegetable oils including soybean oils, gelatin, glycerol, corn or iron oxide
Pregnant or breastfeeding
Known bleeding disorder or coagulopathy or treatment with anticoagulant mechanisms or low platelet counts, abnormal PT or PTT
Impaired glucose tolerance, Type 1 or 2 diabetes
Birth control pills
Alcohol consumption
Other liver disease
Taking any medication that alters triglyceride levels, liver function, blood pressure, glucose or lipid metabolism
Taking over the counter supplements that affect triglycerides or lipid metabolism including fish oil supplements
Treatment for or diagnosis of thyroid disorder or have an elevated TSH at baseline
Use of any antipsychotic medication
Taking chronic anti-inflammatory medications
Less than 100 pounds (45 kg)