Mobilization of Endothelial Progenitor Cells and Aspirin

Hypertrophic Obstructive Cardiomyopathy Clinical Trial

— TROPHIC 3  

Official title:

Mobilization of Endothelial Progenitor Cells Following Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy: Randomized Controlled Trial of Aspirin

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02674958
• Other study ID #: 20150432
• Status: Terminated
• Phase: Phase 3
• Start date: May 2016
• Est. completion date: April 1, 2022

Study information

• Verified date: January 2023
• Source: Ottawa Heart Institute Research Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 6
• Est. completion date: April 1, 2022
• Est. primary completion date: April 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiomyopathies
• Cardiomyopathy, Hypertrophic
• Hypertrophic Obstructive Cardiomyopathy
• Hypertrophy

Intervention

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

Locations

Country	Name	City	State
Canada	University of Ottawa Heart Institute	Ottawa	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
Ottawa Heart Institute Research Corporation

Country where clinical trial is conducted

Canada, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Peak SDF-1 level	Change in level of SDF-1 at 0, 1, 6, 24, 72 hours and on day 7 post procedure	0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days
Other	Peak angiopoietin-1 level	Change in level of angiopoietin-1 at 0, 1, 6, 24, 72 hours and day 7 post procedure	0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days
Other	Peak angiopoietin-2 level	Change in level of angiopoietin-2 at 0, 1, 6, 24, 72 hours and on day 7 post procedure	0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days
Other	Peak tie-2 level	Change in level of tie-2 at 0, 1, 6, 24, 72 hours and on day 7 post procedure	0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days
Other	Peak vascular endothelial growth factor (VEGF) level	Change in level of VEGF at 0, 1, 6, 24, 72 hours and on day 7 post procedure	0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days
Primary	Maximum circulating endothelial progenitor cells as a ratio to baseline at any timepoint	Change in number of EPCs measured at 0 (baseline), 1, 6, 24, 72 hours and on day 7 post procedure	0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days
Secondary	Endothelial cell migration in vitro compared to baseline at any timepoint	Change in endothelial migration measured at 0,1, 6, 24, 72 hours and on day 7 post procedure	0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days