Effects of Prescription Omega-3 Acids on Glucose and Lipoprotein Lipids in Subjects With Hypertriglyceridemia

Study Overview
=================
Brief Summary
-----------------
The objectives of this study are to assess the effects of 4 g/d prescription omega-3 acid ethyl esters (POM3), compared with a placebo, on indices of insulin sensitivity and secretion, as well as aspects of the fasting and postprandial lipid and lipoprotein profiles, in subjects with hypertriglyceridemia.

Detailed Description
-----------------
This trial will utilize a randomized, double-blind, two-period crossover design. At Visit 2 (Week 0), subjects meeting all entry criteria will be randomized to one of two treatment sequences: placebo or POM3 for the first 6 week phase followed by the study product they did not receive during the first phase (POM3 or placebo) for the second 6 weeks. There will be a 2-week washout period between treatment phases.

Official Title
-----------------
A Double-blind, Randomized, Placebo-controlled, Crossover Trial to Assess the Effects of 4 g/d Prescription Omega-3 Acid Ethyl Esters on Indices of Glucose Homeostasis and Lipoprotein Lipids in Subjects With Hypertriglyceridemia

Conditions
-----------------
Hypertriglyceridemia

Intervention / Treatment
-----------------
* Drug: POM3
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and postmenopausal women, ages 18-79 years. Fasting, triglyceride (TG) level in the borderline high to high range. Fasting, low density lipoprotein cholesterol (LDL-C) below the very high range while on no lipid altering therapy or while taking stable-dose statin therapy Provide written informed consent and authorization for protected health information Exclusion Criteria: Use of any lipid-altering medications, which cannot be stopped, except stable dose statin therapy. Use of any omega-3 fatty acid ethyl ester medications or dietary supplements with >1.0 g/d of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), or a combination of EPA and DHA coronary heart disease (CHD) or a CHD risk equivalent Body mass index over 45 kg per square meter Allergy or sensitivity to omega-3 fatty acids, corn or corn products (e.g., corn oil), D-alpha tocopherol (vitamin E) or any ingredients in the study drug Certain muscle, liver, kidney, lung or gastrointestinal conditions Poorly controlled hypertension Certain medications Active cancers treated within prior 2 years (except non-melanoma skin cancer)

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: POM3<br>POM3 for the first six weeks of treatment. Placebo for the second six weeks of treatment | Drug: POM3<br>* 4 g/day<br>* Other names: prescription omega-3 acid ethyl esters;|
| Placebo Comparator: Placebo<br>Placebo for the first six weeks of treatment. POM3 for the second six weeks of treatment | Drug: Placebo<br>* matching placebo capsule, 4 g/day<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference Between Treatments in Liquid Meal Tolerance Test (LMTT) Matsuda Insulin Sensitivity Index (MISI). | Liquid meal tolerance test (LMTT) = two 8 oz servings of Ensure (Abbott Nutrition) + study product followed by blood sample collection at -5, -1, 30, 60, 90, 120, 180, and 240 min, where t = 0 was start of liquid meal consumption. MISI calculated as 10,000/square root of (pre-meal glucose x pre-meal insulin x mean 120 min post-meal glucose x mean 120 min post-meal insulin) | End of Treatment Intervention Phase I (week 6) and End of Treatment Intervention Period II (week 14) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference Between Treatments in LMTT Insulin Secretion Index and Disposition Index. | Insulin secretion index = total area under the curve from 0 to 120 min post-meal for plasma insulin divided by total area under the curve from 0 to 120 min post-meal for plasma glucose. Disposition index = MISI x insulin secretion index | End of Treatment Intervention Phase I (week 6) and End of Treatment Intervention Period II (week 14) |