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

The Genetic Effect on Omega 3 Fatty Acid Supplementation for the Treatment of Non Alcoholic Fatty Liver Disease in Obese Children and Adolescents

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.

Study Overview

• Status: Completed
• Conditions: Hypertriglyceridemia; Steatohepatitis; Non Alcoholic Fatty Liver Disease; Alanine Aminotransferase, Plasma Level of, Quantitative Trait Locus 1
• Intervention / Treatment: Other: Omega diet

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 Type: Interventional
• Enrollment (Actual): 17
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 19 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reduction in hepatic fat fraction	subjects follow study designed meal plan	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
reduction in triglycerides	subjects follow study designed meal plan	12 weeks
lower ALT levels	subjects follow study designed meal plan	12 weeks

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Principal Investigator: Nicola Santoro, MD/PhD, Yale University

Publications and helpful links

General Publications

• Van Name MA, Savoye M, Chick JM, Galuppo BT, Feldstein AE, Pierpont B, Johnson C, Shabanova V, Ekong U, Valentino PL, Kim G, Caprio S, Santoro N. A Low omega-6 to omega-3 PUFA Ratio (n-6:n-3 PUFA) Diet to Treat Fatty Liver Disease in Obese Youth. J Nutr. 2020 Sep 1;150(9):2314-2321. doi: 10.1093/jn/nxaa183.

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 1, 2012
• Primary Completion (ACTUAL): February 1, 2017
• Study Completion (ACTUAL): February 1, 2017

Study Registration Dates

• First Submitted: March 12, 2012
• First Submitted That Met QC Criteria: March 15, 2012
• First Posted (ESTIMATE): March 16, 2012

Study Record Updates

• Last Update Posted (ACTUAL): April 28, 2017
• Last Update Submitted That Met QC Criteria: April 26, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: hypertriglyceridemia; fatty liver; elevated liver enzymes
• Additional Relevant MeSH Terms: Digestive System Diseases; Metabolic Diseases; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease; Hypertriglyceridemia
• Other Study ID Numbers: 1112009408; R01HD040787 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO