- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01285362
Fish Oil and Nonalcoholic Fatty Liver Disease (NAFLD) Study
Fish Oil for the Treatment of Nonalcoholic Fatty Liver Disease in Children
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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New York
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New York, New York, United States, 10032
- Irving Clinical Research Center (GCRC) at Columbia University Medical Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
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 docosahexaenoic acid (DHA).
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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 Names:
|
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.
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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 Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Participants With Normalized Liver Enzyme Levels
Time Frame: Up to 12 months from entry into the study
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To evaluate the number of participants (young adults with obesity related NAFLD) that will normalize their elevated liver enzyme levels (normalized defined as having liver enzyme levels within a normal laboratory range) with supplements of fish oil (n-3 FA containing eicosapentanoic acid and docosahexaenoic acid).
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Up to 12 months from entry into the study
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Number of Participants With Normalization of Plasma Lipid Levels
Time Frame: Up to 12 months from entry into the study
|
The number of participants (young adults with obesity-related NAFLD and associated dyslipidemia) that will normalize plasma lipid levels (normalized defined as having plasma lipid levels within a normal laboratory range) after fish oil supplementation.
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Up to 12 months from entry into the study
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Number of Participants With Insulin Resistance Attenuated
Time Frame: Up to 12 months from entry into the study
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The number of participants (young adults with obesity related NAFLD and insulin resistance) that will attenuate insulin resistance (attenuation of insulin resistance defined as decrease in the body's need for insulin and measured by insulin levels and estimation of Homeostatic model assessment (HOMA-R) after fish oil supplementation.
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Up to 12 months from entry into the study
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Mercedes Martinez, MD, Columbia University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- AAAF0695
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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