Omega 3 Fish Oil Supplements vs. Placebo for Patients With Non-alcoholic Steatohepatitis (NASH)

Study Overview
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Brief Summary
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Nonalcoholic steatohepatitis (NASH) occurs in 2-3% of the US population and carries a 15-20% chance of progression to cirrhosis. It is closely associated with obesity, hyperlipidemia and insulin resistance. Therapy usually includes recommendations to increase exercise and to begin weight reducing diets but these goals are variably achieved and their relative effects in conjunction with pharmacological intervention have not been well defined. Moreover, these lifestyle changes can confound results of treatment trials if not quantified through conditioning testing and measures of body fat. Polyunsaturated fatty acids, especially formulation rich in omega-3, are widely accepted and endorsed in the medical community for their beneficial effects on hyperlipidemia and coronary disease risk reduction. Recent data suggests that omega-3 fatty acids ameliorate hepatic steatosis in humans and in animal models of NASH by reducing hepatic fat content. We hypothesize that a one year course of omega-3 fatty acid (3gm/day) will produce improvement in NASH histological injury independent of changes in weight (BMI) or degree of conditioning measured by the lactate threshold. The effects of the supplement will be compared to a placebo group and controlled for these lifestyle changes.

Official Title
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Omega 3 Fish Oil Supplements vs. Placebo for Patients With Non-alcoholic Steatohepatitis (NASH)

Conditions
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Non-alcoholic Steatohepatitis, Fatty Liver

Intervention / Treatment
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* Drug: Omega 3 Fish Oil supplements
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: NASH with NAS (NASH Activity Score) of >4 evident on a biopsy performed within 6 months of enrollment. Age 21 years or older. BMI 25 or greater. Ability to provide informed consent. Exclusion Criteria: Cirrhosis evident clinically or on biopsy. Secondary forms of NASH such as that seen with bariatric surgery or medication induced from such medications as methotrexate, amiodarone, tamoxifen, corticosteroids. Current or past history of diabetes or hyperlipidemia requiring specific drug therapy (see below). Current use of a weight loss medicine, such as a 'fat-burner' or similar agent Alcohol consumption > 30 g/day, currently or for more than 3 consecutive months within 5 years. Other liver disease (hepatitis C,B, Wilson's, autoimmune, ct-1-antitrypsin and hemochromatosis or HIV Pregnancy or unwillingness to use an effective form of birth control for women of child bearing years. Renal insufficiency (creatinine > 2), symptomatic coronary, peripheral or neurovascular disease, symptomatic heart failure or advanced respiratory disease requiring oxygen therapy. Inability to provide informed consent. Any condition in the opinion of the primary investigator that would contraindicate the patient's participation.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Omega 3 recipient arm<br> | Drug: Omega 3 Fish Oil supplements<br>* Subjects in this arm will receive 3 grams daily Omega 3 fish oil supplements<br>* Other names: Fish Oil capsules;|
| Placebo Comparator: Placebo<br>Placebo fish oil | Drug: Placebo<br>* Fish oil placebo pills<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary endpoint will be improvement in a composite score of histological injury as measured by the NASH Activity Score (NAS). |  | approximately 12 months from enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement of anthropometric indices (weight, BMI, waist circumference) |  | 12 months | 
| Index of cardiorespiratory fitness determined by exercise tolerance (measured by lactate threshold on an exercise treadmill) |  | 12 months | 
| Hepatic fat content measured by magnetic resonance imaging |  | 12 months | 
| Changes in fasting plasma lipids, red cell fatty acid content, changes in anti-hyperlipidemia requirements, insulin sensitivity, and markers of inflammation including tumor necrosis factor and C-reactive protein |  | 12 mos | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Steatohepatitis, NASH, NAFLD, omega 3 fatty acids, Exercise conditioning