Lovaza Mechanisms of Action

Study Overview
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Brief Summary
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High levels of triglycerides is a common abnormality found in patients with diabetes and also cardiovascular disease, and may contribute to the risk for both. Omega 3 fatty acids, as found enriched in fish and also in the commercial agent called Lovaza lower triglyceride levels. Prior work from the investigators group demonstrated that an enzyme responsible for the break down of triglycerides - lipoprotein lipase - generates molecules that can activate a specific nuclear receptor known as PPAR-alpha. This study investigates the hypothesis that taking Lovaza shifts the specific fatty acid content of triglyceride containing lipoproteins and increases the ability of those lipoproteins to activate PPAR-alpha.

Detailed Description
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This study will investigate changes in lipid and other metabolic parameters as well as the ability of isolated lipoproteins to activate PPARs in the presence or absence of lipoprotein lipase in a cohort of normal healthy individuals with modest hypertriglyceridemia before and after a course of Lovaza.

Official Title
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Study of the Effects of Lovaza (Omega 3 Fatty Acids) On Lipoprotein Particles and Their Transcriptional Effects

Conditions
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Moderate Hypertriglyceridemia.

Intervention / Treatment
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* Dietary Supplement: Omega 3 fatty acid (Lovaza)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Otherwise healthy 21 to 65 year old men and women Triglycerides >150 < 500 mg/dL Exclusion Criteria: Other lipid lowering medication including fish oil Major illnesses Diabetes Cardiovascular disease Abnormalities uncovered on screening blood work including undiagnosed diabetes, abnormal liver function tests, triglycerides > 500 mg/dL Indication for immediate statin therapy Pregnancy Contraindication for fish oil use or muscle biopsy

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Dietary Supplement: Omega 3 fatty acid (Lovaza)|Lovaza is an FDA approved omega 3 fatty acid taken as 4 grams a day (two one gram formulations twice a day).|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in lipoprotein metabolite content and their ability to activate PPAR-alpha in an established cell culture system. | Enrolled subjects will serve as their own controls and will be studied at baseline and after 3 months of Lovaza. The primary endpoint will test changes in lipoproteins as a function of their content and ability to activate PPAR-alpha in standard transfected cell culture systems. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in plasma markers for atherosclerosis | Subjects will also be studied before and after Lovaza for changes in lipid profile and c- reactive protein | 3 months | 
| Change in plasma markers of diabetes | Plasma markers of diabetes will be measure before and after Lovaza treatment for 3 months, specifically glucose and A1C levels | 3 months | 
| Changes in plasma markers of liver function | Plasma levels of liver function tests, specifically ALT and AST before and after 3 months of Lovaza. This is not a safety issue since elevated triglycerides can cause increased liver function tests and fish oil (like Lovaza) can lower triglyceride levels and hence ALT and AST levels. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypertriglyceridemia, Fish oil, Omega 3 fatty acids