The Effects of Omega-3 Fatty Acids on Peripheral Arterial Disease II

Study Overview
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Brief Summary
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Investigators hypothesize that high-dose n-3 polyunsaturated fatty acids (PUFA) oral supplementation will improve systemic inflammation, vascular function, and symptomatic status of patients with PAD. Investigators will explore novel mechanistic pathways by which n-3 PUFA affect PAD, evaluating the role of specialized lipid mediators involved in the resolution of inflammation.

Detailed Description
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The OMEGA-PAD II trial will be a 1:1 randomized, double-blinded trial comparing oral supplementation of n-3 PUFA (4.4g/day) to placebo in claudicants (Rutherford stage 1-3) for 3 months. Eligible patients will be screened according to specified inclusion and exclusion criteria. All patients will be treated per our current practice as reflected in the American Heart Association Practice guidelines on PAD. Blood draws, vascular function testing and 6-minute walking tests will be performed at baseline and after 3 months. n-3 PUFA supplementation will be achieved with 4 capsules of Pro-Omega twice daily (Nordic Naturals, Watsonville, California, USA), corresponding to a total of 4.4g/day. Each ProOmega capsule contains 325mg of EPA and 225mg of DHA. The placebo group will take the same number of capsules containing inactive substance (soybean; Nordic Naturals), designed to be the same color and shape as the treatment capsules.

Official Title
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The Effects of Omega-3 Fatty Acids Supplementation on Endothelial Function and Inflammation II

Conditions
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Peripheral Arterial Disease

Intervention / Treatment
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* Dietary Supplement: Pro-Omega
* Other: ProOmega Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Intermittent claudication (Rutherford 1-3) One of the following: Resting or exercise ankle-brachial index (ABI) <0.9 toe pressure < 70 mm Hg documentation on imaging of greater than or equal to 50% stenosis in segments of aortoiliac arteries, femoral arteries, or tibial arteries Age 50 and more Exclusion Criteria: Critical limb ischemia Hypersensitivity/allergies to fish or seafood Already on n-3 PUFA or equivalent Significant renal, hepatic, and inflammatory disease Concurrent severe infections Acute illness (myocardial infarction, stroke, major surgery within 30 days) Receiving immunosuppressive medications or steroids Age < 50

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 100 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 |
| --- | --- |
| Experimental: Pro-Omega<br>High-dose, short-duration dietary omega-3 fatty acids supplementation; 325mg of EPA and 225mg of DHA per capsule. 4.4gm/day x 3 months (Nordic Naturals, Watsonville, CA, USA) | Dietary Supplement: Pro-Omega<br>* Pro-Omega (Nordic Naturals, Watsonville, CA, USA). Each ProOmega capsule contains 325mg of EPA and 225mg of DHA. 4.4gm/day x 3 months<br>|
| Placebo Comparator: Placebo<br>Pro-Omega Placebo soybean capsules (Nordic Naturals, Watsonville, CA, USA); 4.4gm/day x 3 months | Other: ProOmega Placebo<br>* Placebo Comparator: soybean (Nordic Naturals, Watsonville, CA, USA); 4.4gm/day x 3 months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Systemic Inflammatory bio-markers | reduce circulating pro-inflammatory markers (PIMs) and increase pro-resolution mediators (PRMs) assayed using targeted metabolo-lipidomics, increase PRM production within peripheral circulating monocytes. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial Function | Will increase brachial artery flow-mediated vasodilation (FMD)and peripheral resistance (AiX) and decrease arterial stiffness in the lower extremities (PWV). | 3 months |