Clinical trial NCT02674958: Mobilization of Endothelial Progenitor Cells and Aspirin
Official title: Mobilization of Endothelial Progenitor Cells Following Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy: Randomized Controlled Trial of Aspirin
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Hypertrophic Obstructive Cardiomyopathy
Keywords: endothelial progenitor cells
aspirin
acetylsalicylic acid
alcohol septal ablation
Lead sponsor: Ottawa Heart Institute Research Corporation
Sponsor class: OTHER
First posted: 2016-02-05
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximum circulating endothelial progenitor cells as a ratio to baseline at any timepoint
timeFrame: 0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days
Secondary outcomes:
measure: Endothelial cell migration in vitro compared to baseline at any timepoint
timeFrame: 0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days
Other outcomes:
measure: Peak SDF-1 level
timeFrame: 0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days
measure: Peak angiopoietin-1 level
timeFrame: 0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days
measure: Peak angiopoietin-2 level
timeFrame: 0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days
measure: Peak tie-2 level
timeFrame: 0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days
measure: Peak vascular endothelial growth factor (VEGF) level
timeFrame: 0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days
Locations:
city: Ottawa
country: Canada
facility: University of Ottawa Heart Institute
state: Ontario
Study officials:
affiliation: OHIRC
name: Aun-Yeong Chong, MD, MRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1111/j.1745-7254.2006.00298.x.
citation: 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.
citation: 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.