Trial record 1 of 1 for:    ALANINE AMINOTRANSFERASE, PLASMA LEVEL OF, QUANTITATIVE TRAIT LOCUS 1
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Genetic Effect on Omega 3 Fatty Acids for the Treatment of Fatty Liver Disease

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Yale University
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Sonia Caprio, Yale University
ClinicalTrials.gov Identifier:
NCT01556113
First received: March 12, 2012
Last updated: June 16, 2014
Last verified: June 2014
  Purpose

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.


Condition Intervention
Non Alcoholic Fatty Liver Disease
Steatohepatitis
Hypertriglyceridemia
Alanine Aminotransferase, Plasma Level of, Quantitative Trait Locus 1
Dietary Supplement: Lovaza
Other: Omega diet

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • reduction in hepatic fat fraction [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 120
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)
Arms Assigned Interventions
Experimental: Lovaza
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.

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. 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.

  Eligibility

Ages Eligible for Study:   10 Years to 19 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  • Can not swallow pills
  • Less than 100 pounds (45 kg)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01556113

Contacts
Contact: Bridget Pierpont, M.A. 203-785-2942 bridget.pierpont@yale.edu

Locations
United States, Connecticut
Yale School of Medicine Recruiting
New Haven, Connecticut, United States, 06510
Contact: Bridget Pierpont, M.A.    203-785-2942    bridget.pierpont@yale.edu   
Contact: Grace Kim, M.D.       grace.kim@yale.edu   
Principal Investigator: Grace Kim, M.A./M.D.         
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Grace Kim, M.D. Yale University, attending
Principal Investigator: Nicola Santoro, MD/PhD Yale University
  More Information

No publications provided

Responsible Party: Sonia Caprio, Principal Investigator, Yale University
ClinicalTrials.gov Identifier: NCT01556113     History of Changes
Other Study ID Numbers: 1112009408, R01HD040787
Study First Received: March 12, 2012
Last Updated: June 16, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
fatty liver
hypertriglyceridemia
elevated liver enzymes

Additional relevant MeSH terms:
Fatty Liver
Hypertriglyceridemia
Liver Diseases
Digestive System Diseases
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 22, 2014