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

NCT ID: NCT01556113

Last Updated: 2017-04-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2017-02-28

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.

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.

Conditions

Non Alcoholic Fatty Liver Disease; Steatohepatitis; Hypertriglyceridemia; Alanine Aminotransferase, Plasma Level of, Quantitative Trait Locus 1

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

omega diet carrying CC/CG genotype

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

Group Type: ACTIVE_COMPARATOR

Omega diet

Intervention Type: OTHER

Eligible subjects will receive omega rich diet for 12 weeks with weekly appointments to obtain food records, draw serum samples and provide meals.

omega diet carrying GG genotype

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

Group Type: ACTIVE_COMPARATOR

Omega diet

Intervention Type: OTHER

Eligible subjects will receive omega rich diet for 12 weeks with weekly appointments to obtain food records, draw serum samples and provide meals.

Interventions

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.

Intervention Type: OTHER

Eligibility Criteria

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)

• Minimum Eligible Age: 10 Years
• Maximum Eligible Age: 19 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

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

NIH

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nicola Santoro, MD/PhD

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale School of Medicine

New Haven, Connecticut, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32652034 (View on PubMed)

Other Identifiers

R01HD040787

Identifier Type: NIH

Identifier Source: secondary_id

View Link

1112009408

Identifier Type: -

Identifier Source: org_study_id