Body Weight, Aspirin Dose and Pro-resolving Mediators

Study Overview
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Brief Summary
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This study employs a placebo-controlled randomized cross-over design to investigate the impact of body weight and aspirin dose on levels of specialized pro-resolving lipid mediators in blood and neutrophils.

Official Title
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DISCOVER: A Single-site Double-blind Placebo-controlled Randomized Mechanistic Crossover Trial to Assess the Influence of boDy weIght on aSpirin-triggered speCialized prO-resolVing mEdiatoRs

Conditions
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Body Weight

Intervention / Treatment
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* Drug: Aspirin 81mg
* Drug: Aspirin 325mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1. Age between 40 and 70 years Exclusion Criteria: Anti-platelet medication use in the past 7 days Aspirin intolerance or allergy Known bleeding or clotting disorder Chronic inflammatory or connective tissue disease Immunological deficiency Diabetes mellitus Prior gastric or bariatric surgery Active smoking Platelet count <100,000 Use of omega-3 fatty acid supplementation Use of drugs or supplements known to inhibit COX-1/COX-2/lipoxygenases Corticosteroid use Recent initiation or change in dose of statin therapy Pregnancy

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 70 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This is a two-phase crossover design with run-in and wash out periods prior to each phase.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Aspirin 81mg, Then Aspirin 325mg<br>After a 3 week placebo run-in period, participants first receive Aspirin 81mg capsule daily for 3 weeks. After a placebo washout period of 3 weeks, they then receive Aspirin 325mg capsule daily for another 3 weeks. | Drug: Aspirin 81mg<br>* 81mg oral capsule<br>Drug: Aspirin 325mg<br>* 325mg oral capsule<br>|
| Experimental: Aspirin 325mg, Then Aspirin 81mg<br>After a 3 week placebo run-in period, participants first receive Aspirin 325mg capsule daily for 3 weeks. After a placebo washout period of 3 weeks, they then receive Aspirin 81mg capsule daily for another 3 weeks. | Drug: Aspirin 81mg<br>* 81mg oral capsule<br>Drug: Aspirin 325mg<br>* 325mg oral capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Serum 15R-LXA4 |  | Week 3, Week 6 | 
| Change in Serum 15R-LXA4 |  | Week 9, Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in serum and neutrophil supernatant lipid mediators |  | Week 3, Week 6 | 
| Change in serum and neutrophil supernatant lipid mediators |  | Week 9, Week 12 | 
| Change in platelet-monocyte aggregates |  | Week 3, Week 6 | 
| Change in platelet-monocyte aggregates |  | Week 9, Week 12 | 
| Change in platelet-neutrophil aggregates |  | Week 3, Week 6 | 
| Change in platelet-neutrophil aggregates |  | Week 9, Week 12 | 
| Change in platelet surface expression of CD62P |  | Week 3, Week 6 | 
| Change in platelet surface expression of CD62P |  | Week 9, Week 12 | 
| Change in leukocyte expression of ALX/FPR2 |  | Week 3, Week 6 | 
| Change in leukocyte expression of ALX/FPR2 |  | Week 9, Week 12 | 
| Change in leukocyte expression of GPR32 |  | Week 3, Week 6 | 
| Change in leukocyte expression of GPR32 |  | Week 9, Week 12 | 
| Change in leukocyte expression of ERV1/ChemR23 |  | Week 3, Week 6 | 
| Change in leukocyte expression of ERV1/ChemR23 |  | Week 9, Week 12 | 
| Change in leukocyte expression of BLT1 |  | Week 3, Week 6 | 
| Change in leukocyte expression of BLT1 |  | Week 9, Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Aspirin