Fish Oil and Nonalcoholic Fatty Liver Disease (NAFLD) Study

The recruitment status of this study is unknown because the information has not been verified recently.
Verified February 2012 by Columbia University.
Recruitment status was  Not yet recruiting
Sponsor:
Collaborator:
GlaxoSmithKline
Information provided by (Responsible Party):
Columbia University
ClinicalTrials.gov Identifier:
NCT01285362
First received: January 26, 2011
Last updated: February 14, 2012
Last verified: February 2012
  Purpose

Over the past 30 years, the prevalence of childhood obesity in the United States has tripled from 5% to 15%. Major consequences of obesity include insulin resistance, type- 2 diabetes, cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). The liver pathology encompasses a range from isolated fatty liver to advanced fibrosis, cirrhosis and end-stage liver disease. Weight loss, particularly if gradual, may lead to improvement in liver histology. Unfortunately, few patients in the pediatric population are willing to follow these recommendations and achieve weight loss. Medical treatment directed specifically at the liver disease has only recently been investigated and approved in patients with NAFLD. The beneficial effects of fish oil are attributed to its high concentrations of n - 3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are major regulators of pathways that participate in decreased production and break down of triglycerides and fatty acids in the liver. We hypothesize that children with obesity related NAFLD will normalize elevated liver enzymes, plasma lipid levels, and attenuate insulin resistance with supplements of n-3 fatty acids. If this hypothesis is proven true, then fish oil could be used to treat NAFLD and to prevent the deterioration of fatty liver into end-stage liver disease.


Condition Intervention
Non-Alcoholic Fatty Liver Disease
Drug: Fish Oil Supplementation
Drug: Placebo Supplementation

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Fish Oil for the Treatment of Nonalcoholic Fatty Liver Disease in Children

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • 1. To evaluate whether young adults with obesity related NAFLD will normalize their elevated liver enzyme levels with supplements of fish oil (n-3 FA containing eicosapentanoic acid and decosahexaenoic acid). [ Time Frame: Up to 12 months from entry into the study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Attenuation of insulin resistance [ Time Frame: Up to 12 months from entry into the study ] [ Designated as safety issue: No ]
    1. To evaluate whether young adults with obesity-related NAFLD and associated dyslipidemia will normalize their plasma lipid levels after fish oil supplementation.
    2. To evaluate whether young adults with obesity related NAFLD and insulin resistance will attenuate their insulin resistance (as measured by insulin levels and estimation of HOMA-R) after fish oil supplementation.


Estimated Enrollment: 20
Study Start Date: February 2012
Estimated Study Completion Date: November 2012
Estimated Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Fish Oil Supplementation (Group A)
Group A will receive fish oil capsules, containing n3-Fatty Acids, at a dose of 4g/day. Each 1g capsule will contain 465mg of EPA and 375 mg of DHA.
Drug: Fish Oil Supplementation
Group A will receive fish oil capsules, containing n3-Fatty Acids, at a dose of 4g/day. Each 1g capsule will contain 465mg of EPA and 375 mg of DHA.
Other Name: Fish Oil Pills
Placebo Comparator: Placebo Supplementation (Group B)
Group B will receive corn oil in the capsules at the same dose as Group A. The corn oil capsules will appear identical in size and color to the fish oil capsules.
Drug: Placebo Supplementation
Group B will receive corn oil in the capsules at the same dose as Group A. The corn oil capsules will appear identical in size and color to the fish oil capsules.
Other Name: Placebo Pills

Detailed Description:

Scientific Abstract:

Over the past 30 years, the prevalence of childhood obesity in the United States has tripled from 5% to 15%. Overweight is defined as a body mass index (BMI) above the 95%centile for age and gender. The recent estimates of obesity prevalence based on the National Health and Nutrition Examination Study (NHANES) 1999-2000 suggest that 15.3% to 15.5% of 6-19 year old children have a BMI above the 95% centile for age. Major consequences of obesity include insulin resistance, type 2 diabetes mellitus, cardiovascular disease and nonalcoholic fatty liver disease (NAFLD). NAFLD represents a spectrum of conditions characterized by macrovesicular hepatic steatosis. The liver pathology encompasses a range from isolated fatty liver to steatohepatitis, advanced fibrosis, cirrhosis and end-stage liver disease. Nonalcoholic steatohepatitis (NASH) may progress to cirrhosis even in children. Weight loss, particularly if gradual, may lead to improvement in liver histology. Unfortunately, few patients in the pediatric population are willing to follow these recommendations and achieve weight loss. Pharmacological therapy directed specifically at the liver disease has only recently been investigated in patients with NAFLD. Most of these studies have been uncontrolled pilot studies, lasting one year or less and have produced equivocal results. Thus, there is currently no effective treatment for this disorder. The beneficial effects of fish oil are attributed to its high concentrations of n - 3 fatty acids: eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Long-chain polyunsaturated n-3 FA (LCPUFA) are major regulators of molecular pathways altering many areas of cellular and organ function, metabolism and gene expression, and are active in reducing inflammation through the eicasanoid pathway. N-3 LCPUFA are well established negative regulators of hepatic lipogenesis. Recently it has been shown that the suppressive effects of n-3 LCPUFA on lipogenic enzymes are mediated by the reduction of mature SREBP-1c protein in the liver, a key transcription factor that activates transcription of genes involved in fatty acid synthesis. It is also well established today that the n-3 LCPUFA act as PPAR-alpha and gamma modulators, important in triglyceride (TG) and fatty acid catabolism. N-3 LCPUFA produce a dramatic increase in the size and number of hepatic peroxisomes and increase the capacity of the hepatocyte to metabolize fatty acids by inducing peroxisomal beta-oxidation enzymes, such as acyl CoA oxidase . We hypothesize that children with obesity related NAFLD will normalize elevated liver enzymes, plasma lipid levels, and attenuate insulin resistance with supplements of n-3 LCPUFA. If this hypothesis is proven true, then fish oil could be used to treat NAFLD and to prevent the deterioration of fatty liver into end-stage liver disease.

We will study 20 patients with NAFLD and hypertriglyceridemia, age 12y and above. Excluded from the study will be those with evidence of chronic infectious hepatitis, metabolic liver disease, autoimmune and chronic cholestatic liver diseases, insulin dependent diabetes and those with history of alcohol consumption, or exposure to drugs or hepatotoxins. Those qualifying for this study will be age 12 and above obese individuals (BMI > 95% for age), who have hyperlipidemia, but will have normal fasting glucose levels. For inclusion all will have elevation of serum aminotransferases to at least 1.5 times the upper limit of normal for a minimum of 3 months and evidence of fatty liver by abdominal ultrasound and liver biopsy. Patients will be randomized to placebo dummy capsules (controls) or n-3 LCPUFA supplements (Lovaza - GSK Pharmaceuticals, provided free of charge) at a dose of 4gr/day. They will be followed up at 3 and 6 months; monitoring height, weight, BMI, liver enzyme levels (ALT, AST, ALP), bilirubin total and direct, GGT, plasma phospholipids, plasma lipids, insulin levels and estimation of HOMA-R.

  Eligibility

Ages Eligible for Study:   12 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Body Mass Index (BMI i.e. wt(Kg)/ht(m)2) above the 95th % as defined by the NHANES tables.
  • Elevated liver enzymes (ALT and/or AST) to at least 1.5 times the upper limit on at least 2 examinations, (ALT, the upper limit of normal values in our laboratory is 41 U/L; AST, upper limit of normal values in our laboratory is 38 U/L).
  • Subjects must demonstrate ability to swallow capsules.

Exclusion Criteria:

  • Overt Diabetes
  • Viral or autoimmune hepatitis, Wilson's disease, Alpha-1 antitrypsin deficiency, hemochromatosis or any other form of chronic liver disease not related to NAFLD
  • Exposure to drugs or hepatotoxins less than 14 days prior to recruitment
  • Alcohol consumption > 20 grams/day
  • Evidence of cirrhosis on liver biopsy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01285362

Contacts
Contact: Diana Volpert, MD 212-305-5903 ext 2-1853 dv2029@columbia.edu

Locations
United States, New York
Irving Clinical Research Center (GCRC) at Columbia University Medical Center Not yet recruiting
New York, New York, United States, 10032
Contact: Diana Volpert, MD    212-305-5903 ext 2-1853    dv2029@columbia.edu   
Sponsors and Collaborators
Columbia University
GlaxoSmithKline
Investigators
Principal Investigator: Diana Volpert, MD Columbia University
  More Information

No publications provided

Responsible Party: Columbia University
ClinicalTrials.gov Identifier: NCT01285362     History of Changes
Other Study ID Numbers: AAAF0695
Study First Received: January 26, 2011
Last Updated: February 14, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
Fatty Liver Disease
Hepatic Steatosis
Docosahexaenoic Acid
Eicosapentanoic Acid
Omega-3 Fatty Acids
Elevated Transaminases
Fish oil supplements

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases

ClinicalTrials.gov processed this record on April 22, 2014