THE OMEGA-SPM-DOSE and OMEGA-SPM-PAD: Specialized Pro-Resolving Mediators in Patients With Peripheral Artery Disease

Study Overview
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Brief Summary
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The purpose of this study is to understand the effects of fish oil supplement (containing parts of omega-3 fatty acids) on inflammation. The investigators are aiming to identify which dose of the fish oil supplement is the most effective. The name of the fish oil supplement is SPM Emulsion.

Detailed Description
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The OMEGA-SPM-DOSE trial and the OMEGA-SPM-PAD trial are two parts of a pilot study which aims to investigate the effect of a novel formulation of a nutritional supplement containing highly concentrated n-3 PUFA metabolites (SPM Emulsion) on the metabolo-lipidomic profile of healthy volunteers and patients with Peripheral Arterial Disease(PAD). Ten healthy volunteers and ten patients with PAD will participate in Part 1a, the OMEGA-SPM-DOSE Study. A follow-up, placebo controlled, prospective study on the best dosing modality determined in Phase 1a will then take place in a PAD and OA population (n=12), Phase 1b - the OMEGA-SPM-PAD Study. Specific measurements will include targeted metabolo-lipidomic profiling, established markers of inflammation, and functional monocyte and macrophage assays. The proposed studies have the potential to provide important new insights on the role of nutritional interventions in PAD.

Official Title
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THE OMEGA-SPM-DOSE and OMEGA-SPM-PAD: Specialized Pro-Resolving Mediators in Patients With Peripheral Artery Disease

Conditions
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Claudication, Peripheral Arterial Disease, Claudication, Intermittent, Vascular Occlusion, Vascular Calcification, Vascular Diseases, Osteoarthritis

Intervention / Treatment
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* Dietary Supplement: SPM Emulsion, Dose-modality
* Dietary Supplement: SPM Softgel, Dose-Modality
* Dietary Supplement: Placebo Softgel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy Volunteers: -Age 20-80 PAD Patients: Mild claudication to rest pain (Rutherford 1-4) Resting or exercise ABI < 0.9 or TBI < 0.6 Age 40 and more OA Patients: -Lower extremity (hip or knee) OA Exclusion Criteria: PAD, OA Patients and Healthy Volunteers: Plan to undergo surgical procedure or PVI for treatment of PAD within one month Evidence of active infection Hypersensitivity or allergy to fish or seafood Already on n-3 PUFA or equivalent Chronic liver disease, end-stage renal disease (CKD 5), or chronic inflammatory disorders Poorly controlled diabetes (HbA1C > 8%) BMI < 20 or >35 Recent other major surgery or illness within 30 days Use of immunosuppressive medications or steroids History of organ transplantation Pregnancy, or plans to become pregnant, or lactating Healthy Volunteers: hsCRP > 2mg/L Regular aspirin use Regular non-steroidal anti-inflammatory drug use
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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1a (OMEGA-SPM-DOSE)<br>PAD patients and healthy volunteers in study for SPM Emulsion, dose-modality. | Dietary Supplement: SPM Emulsion, Dose-modality<br>* Phase 1a Dose-Finding oral SPM administration of increasing dose (15ml, 30ml, and 60ml) by the following schedule: Days 1 to 5: 15 ml; Days 6 to 14: Washout, no SPM administration; Days 15 to 19: 30 ml; Days 20-28: Washout, no SPM administration; Days 29-33: 60 ml<br>* Other names: Specialized Pro-resolving Lipid Mediator Emulsion;|
| Active Comparator: SPM - Phase 1b (OMEGA-SPM-DOSE)<br>PAD and Osteoarthritis (OA) patients using softgel, dose-modality. | Dietary Supplement: SPM Softgel, Dose-Modality<br>* Phase 1b Dose-Finding oral softtel SPM administration of two different doses (2 softgel vs 4 softgel) Days 0 to 5: 2 SPM softgel; Days 6 to 21: Washout, no SPM administration; Days 22 to 26: 4 SPM softgel; Days 27-42: Washout, no SPM administration<br>* Other names: Omega SPM Bridging;|
| Placebo Comparator: Placebo - Phase 1b (OMEGA-SPM-PLACEBO)<br>PAD and Osteoarthritis (OA) patients using softgel, dose-modality. | Dietary Supplement: Placebo Softgel<br>* Days 43-47: 4 Placebo softgel; Day 48-64 Washout<br>* Other names: Omega SPM Bridging;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Optimal Phase 1b Dose | The smallest dose administered in Phase 1a participants which results in an increase in Resolution Index at least 3 times that of baseline, or the subsequent larger dose resulting in a Resolution Index greater than 2 times that of the preceding does with no increase in side effects at the larger dose. | Baseline, Day 33 | 
| Change in the Resolution Index | Integrated metabolo-lipidomics assessment of SPM pathways: Average concentration of 15-HEPE, 18-HEPE, 4-HDHA, and 17-HDHA in plasma. | Baseline, Day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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peripheral arterial disease, claudication, PAD, Vascular Disease, Vascular Occlusion, Vacular Calcification, intermittent claudication, Osteoarthritis