Fish Oil and Nonalcoholic Fatty Liver Disease (NAFLD) Study

NCT ID: NCT01285362

Last Updated: 2022-05-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2014-09-30

Brief Summary

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. The investigators 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.

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 eicosanoid 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.

The investigators 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 - GlaxoSmithKline (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, Gamma-glutamyl transferase (GGT), plasma phospholipids, plasma lipids, insulin levels and estimation of HOMA-R.

Conditions

Non-Alcoholic Fatty Liver Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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 docosahexaenoic acid (DHA).

Group Type: ACTIVE_COMPARATOR

Fish Oil Supplementation

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo Supplementation

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Fish Oil Pills; Placebo Pills

Eligibility 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.

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: collaborator

Columbia University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mercedes Martinez, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

Irving Clinical Research Center (GCRC) at Columbia University Medical Center

New York, New York, United States

Countries

United States

Other Identifiers

AAAF0695

Identifier Type: -

Identifier Source: org_study_id