Mobilization of Endothelial Progenitor Cells and Aspirin

Overview

Aspirin at doses used during acute myocardial infarction may inhibit the mobilization of endothelial progenitor cells (EPCs).

Full Title of Study: “Mobilization of Endothelial Progenitor Cells Following Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy: Randomized Controlled Trial of Aspirin”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Basic Science
    • Masking: Single (Outcomes Assessor)
  • Study Primary Completion Date: December 2022

Detailed Description

Aspirin has been shown to lower the number of EPCs in a time- and concentration-dependent manner. In vitro studies also show that aspirin may reduce the migratory and adhesive capacity of isolated EPCs, inhibit iNOS and tubule formation, which are pre-requisites for angiogenesis. This is relevant when patients are given a loading dose of 325mg at the time of diagnosis of acute myocardial infarction where higher numbers of EPCs have been associated with better outcomes. Furthermore, in the PLATO (Platelet Inhibition and Patient Outcomes) trial, high dose aspirin appeared to counteract the beneficial effect seen when ticagrelor or clopidogrel was used with low doses of aspirin in acute coronary syndromes (ACS). As aspirin is currently standard of care in the management of ACS, it is difficult to conduct a study of the effect of aspirin versus placebo in that scenario. However, during alcohol septal ablation for hypertrophic obstructive cardiomyopathy, the indication for an antiplatelet agent is not well defined and varies between operators. When a small amount of myocardium is deliberately destroyed in this process, it serves as an ideal model to study the effect of aspirin on the biology of EPCs in vivo. This could provide an explanation to the different effects of high versus low dose aspirin when combined with a second antiplatelet agent in the management of ACS.

Interventions

  • Drug: Aspirin
    • Aspirin 325mg bolus followed by 162mg daily until day 7 post alcohol septal ablation

Arms, Groups and Cohorts

  • Active Comparator: Aspirin
    • Aspirin 325mg orally bolus followed by 162mg orally daily during alcohol septal ablation for hypertrophic obstructive cardiomyopathy until day 7.
  • No Intervention: No aspirin
    • No aspirin allowed during alcohol septal ablation for hypertrophic obstructive cardiomyopathy until day 7.

Clinical Trial Outcome Measures

Primary Measures

  • Maximum circulating endothelial progenitor cells as a ratio to baseline at any timepoint
    • Time Frame: 0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days
    • Change in number of EPCs measured at 0 (baseline), 1, 6, 24, 72 hours and on day 7 post procedure

Secondary Measures

  • Endothelial cell migration in vitro compared to baseline at any timepoint
    • Time Frame: 0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days
    • Change in endothelial migration measured at 0,1, 6, 24, 72 hours and on day 7 post procedure

Participating in This Clinical Trial

Inclusion Criteria

1. Patients who have been selected to undergo alcohol septal ablation for hypertrophic obstructive cardiomyopathy based on clinical need 2. Age >18 years, <80 years Exclusion Criteria:

1. Patients with known allergy to aspirin 2. Inability or refusal to consent to participate in the study 3. Patients who are on non-steroidal anti-inflammatory drugs and cannot be stopped for the duration of the study

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: 80 Years

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Ottawa Heart Institute Research Corporation
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Aun-Yeong Chong, MD, MRCP, Principal Investigator, OHIRC
  • Overall Contact(s)
    • Aun-Yeong Chong, MD, MRCP, +1 613 696 7280, achong@ottawaheart.ca

Citations Reporting on Results

Chen TG, Chen JZ, Xie XD. Effects of aspirin on number, activity and inducible nitric oxide synthase of endothelial progenitor cells from peripheral blood. Acta Pharmacol Sin. 2006 Apr;27(4):430-6.

Lou J, Povsic TJ, Allen JD, Adams SD, Myles S, Starr AZ, Ortel TL, Becker RC. The effect of aspirin on endothelial progenitor cell biology: preliminary investigation of novel properties. Thromb Res. 2010 Sep;126(3):e175-9. doi: 10.1016/j.thromres.2009.11.017. Epub 2010 Jul 24.

Etulain J, Fondevila C, Negrotto S, Schattner M. Platelet-mediated angiogenesis is independent of VEGF and fully inhibited by aspirin. Br J Pharmacol. 2013 Sep;170(2):255-65. doi: 10.1111/bph.12250.

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