Mobilization of Endothelial Progenitor Cells and Aspirin (TROPHIC 3)

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ClinicalTrials.gov Identifier: NCT02674958

Recruitment Status : Recruiting

First Posted : February 5, 2016

Last Update Posted : June 21, 2019

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Sponsor:

Information provided by (Responsible Party):

Ottawa Heart Institute Research Corporation

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Hypertrophic Obstructive Cardiomyopathy	Drug: Aspirin	Phase 3

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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	20 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Outcomes Assessor)
Primary Purpose:	Basic Science
Official Title:	Mobilization of Endothelial Progenitor Cells Following Alcohol Septal Ablation in Hypertrophic Obstructive Cardiomyopathy: Randomized Controlled Trial of Aspirin
Actual Study Start Date :	May 2016
Estimated Primary Completion Date :	December 2022
Estimated Study Completion Date :	December 2022

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Familial hypertrophic cardiomyopathy

MedlinePlus related topics: Cardiomyopathy

Drug Information available for: Aspirin

Genetic and Rare Diseases Information Center resources: Aortic Valve Stenosis

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Aspirin Aspirin 325mg orally bolus followed by 162mg orally daily during alcohol septal ablation for hypertrophic obstructive cardiomyopathy until day 7.	Drug: Aspirin Aspirin 325mg bolus followed by 162mg daily until day 7 post alcohol septal ablation Other Name: Acetylsalicylic acid
No Intervention: No aspirin No aspirin allowed during alcohol septal ablation for hypertrophic obstructive cardiomyopathy until day 7.

Outcome Measures

Primary Outcome 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 Outcome 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

Other Outcome Measures:

Peak SDF-1 level [ Time Frame: 0 hour, 1 hour, 6 hours, 24 hours, 72 hours and 7 days ]
Change in level of SDF-1 at 0, 1, 6, 24, 72 hours and on day 7 post procedure
Peak angiopoietin-1 level [ Time Frame: 0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days ]
Change in level of angiopoietin-1 at 0, 1, 6, 24, 72 hours and day 7 post procedure
Peak angiopoietin-2 level [ Time Frame: 0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days ]
Change in level of angiopoietin-2 at 0, 1, 6, 24, 72 hours and on day 7 post procedure
Peak tie-2 level [ Time Frame: 0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days ]
Change in level of tie-2 at 0, 1, 6, 24, 72 hours and on day 7 post procedure
Peak vascular endothelial growth factor (VEGF) level [ Time Frame: 0 hour, 1 hour, 6 hours, 24 hours 72 hours and 7 days ]
Change in level of VEGF at 0, 1, 6, 24, 72 hours and on day 7 post procedure

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02674958

Contacts

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Contact: Aun-Yeong Chong, MD, MRCP	+1 613 696 7280	achong@ottawaheart.ca
Contact: Christopher Glover, MD, FRCPC	+1 613 696 7327	cglover@ottawaheart.ca

Locations

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Canada, Ontario
University of Ottawa Heart Institute	Recruiting
Ottawa, Ontario, Canada, K1Y 4W7
Contact: Poppy MacPhee +1 613 6967000 ext 14646 pmacphee@ottawaheart.ca

Sponsors and Collaborators

Ottawa Heart Institute Research Corporation

Investigators

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Principal Investigator:	Aun-Yeong Chong, MD, MRCP	OHIRC

More Information

Publications of 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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Responsible Party:	Ottawa Heart Institute Research Corporation
ClinicalTrials.gov Identifier:	NCT02674958 History of Changes
Other Study ID Numbers:	20150432
First Posted:	February 5, 2016 Key Record Dates
Last Update Posted:	June 21, 2019
Last Verified:	June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

Keywords provided by Ottawa Heart Institute Research Corporation:


endothelial progenitor cells aspirin acetylsalicylic acid alcohol septal ablation

Additional relevant MeSH terms:

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Cardiomyopathies Cardiomyopathy, Hypertrophic Hypertrophy Heart Diseases Cardiovascular Diseases Pathological Conditions, Anatomical Aortic Stenosis, Subvalvular Aortic Valve Stenosis Heart Valve Diseases Aspirin Ethanol Anti-Infective Agents, Local Anti-Infective Agents Central Nervous System Depressants Physiological Effects of Drugs	Anti-Inflammatory Agents, Non-Steroidal Analgesics, Non-Narcotic Analgesics Sensory System Agents Peripheral Nervous System Agents Anti-Inflammatory Agents Antirheumatic Agents Fibrinolytic Agents Fibrin Modulating Agents Molecular Mechanisms of Pharmacological Action Platelet Aggregation Inhibitors Cyclooxygenase Inhibitors Enzyme Inhibitors Antipyretics

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