Angiogenesis and Fibrosis in Myocardial Infarction

Study Description

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

Angiogenesis and fibrosis lie at the heart of a number of fundamental processes responsible for cardiovascular disease. In this proposal, the investigators intend to build upon a highly successful programme of studies exploring the cardiovascular applications of positron emission tomography. Specifically, the investigators will explore the potential role of a novel radiotracer, 18F-fluciclatide, which is a highly selective ligand for the αvβ3 and αvβ5 integrin receptors that are up regulated during angiogenesis, and tissue fibrosis and remodelling. This tracer has been successfully used to assess angiogenesis in metastatic tumours and its uptake is suppressed by anti-angiogenic therapies. The investigators here propose to describe the pattern of uptake of 18F-fluciclatide in cardiovascular diseases, specifically acute myocardial infarction and aortic atherosclerosis. The investigators will correlate 18F-fluciclatide uptake with in vivo measures of angiogenesis and fibrosis. If successful, this novel radiotracer could provide an extremely important non-invasive method of assessing in vivo angiogenesis, plaque vulnerability, and tissue remodelling as well as potential applications in developing stem cell therapies.

Condition or disease	Intervention/treatment
Myocardial Infarction; Fibrosis; Neovascularization, Pathologic	Procedure: Cardiac MRI scan; Radiation: CT-PET scan; Radiation: CT-coronary angiogram

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Study Design

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Study Type :	Observational
Actual Enrollment :	30 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	The Identification of In Vivo Angiogenesis and Fibrosis in Myocardial Infarction Using Positron Emission Tomography.
Study Start Date :	April 2013
Actual Primary Completion Date :	March 2016
Actual Study Completion Date :	March 2016

Groups and Cohorts

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Group/Cohort	Intervention/treatment
Chronic Coronary Occlusion group; We will also recruit 10 patients with an angiographically documented chronic (>6 months) proximal coronary artery occlusion that has not been revascularised but has extensive collateral coronary blood flow. We will perform CT-coronary angiogram, cardiac MRI scan and CT-PET scan.	Procedure: Cardiac MRI scan; Cardiac MRI scan with assessment of late gadolinium enhancement and T1 mapping. Radiation: CT-PET scan; Computed Tomography / Positron Emission Tomography scan with 18F-fluciclatide tracer. Radiation: CT-coronary angiogram; CT-coronary angiogram following CT-PET scan. Standard protocol.
MI (non-revascularised); These patients (n=15) will undergo Cardiac MRI, CT-PET scan and CT-coronary angiogram scan 2 weeks following their myocardial infarction. They will undergo a second CT-PET scan 9 weeks following their myocardial infarction. They will undergo a second cardiac MRI scan 6 - 12 months following their myocardial infarction.	Procedure: Cardiac MRI scan; Cardiac MRI scan with assessment of late gadolinium enhancement and T1 mapping. Radiation: CT-PET scan; Computed Tomography / Positron Emission Tomography scan with 18F-fluciclatide tracer. Radiation: CT-coronary angiogram; CT-coronary angiogram following CT-PET scan. Standard protocol.
MI (revascularised); These patients (n=15) will undergo Cardiac MRI, CT-PET scan and CT-coronary angiogram scan 2 weeks following their myocardial infarction. They will undergo a second CT-PET scan 9 weeks following their myocardial infarction. They will undergo a second cardiac MRI scan 6 - 12 months following their myocardial infarction.	Procedure: Cardiac MRI scan; Cardiac MRI scan with assessment of late gadolinium enhancement and T1 mapping. Radiation: CT-PET scan; Computed Tomography / Positron Emission Tomography scan with 18F-fluciclatide tracer. Radiation: CT-coronary angiogram; CT-coronary angiogram following CT-PET scan. Standard protocol.

Outcome Measures

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. The primary outcome is heart function determined by ejection fraction (in %) 6 months following a heart attack. [ Time Frame: 6 - 12 months ]

Secondary Outcome Measures :

1. Extent of fibrosis (% late gadolinium enhancement) & blood flow 6 months post-MI, and the correlation with integrin expression at 9 weeks (fluciclatide distribution through the myocardium viewed on CTPET images). [ Time Frame: 1 year ]

Biospecimen Retention:   Samples Without DNA

Blood samples will be taken, and the serum frozen and stored for further analysis pending ethical approval.

Eligibility Criteria

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	40 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Non-Probability Sample

Study Population

40 patients in total , recruited from cardiology inpatient wards or outpatient clinics.

Criteria

Inclusion Criteria:

Patients will be recruited if they are >40 years of age and have sustained a recent large (plasma troponin I concentration >10 ng/mL; upper limit of normal 0.05 ng/mL) acute myocardial infarction defined according to the Universal Definition of myocardial infarction [Thygesen et al, 2007].

We will recruit patients with a major epicardial occlusion that has or has not been revascularised with percutaneous coronary intervention (n=15 per group). We will also recruit 10 patients with an angiographically documented chronic (>6 months) proximal coronary artery occlusion that has not been revascularised but has extensive collateral coronary blood flow.

Exclusion Criteria:

• A known critical (≥95%) left main stem coronary artery stenosis
• Continued symptoms of angina at rest or minimal exertion
• Atrial fibrillation
• Hepatic failure (Childs-Pugh grade B or C)
• Renal failure (estimated glomerular filtration rate <25 mL/min)
• Women of child-bearing potential.
• Inability to undergo scanning
• Contraindication to magnetic resonance imaging

Contacts and Locations

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United Kingdom
University of Edinburgh
Edinburgh, Lothian, United Kingdom, EH16 4TJ

Sponsors and Collaborators

University of Edinburgh

Investigators

Principal Investigator:	William SA Jenkins, MBChB	University of Edinburgh / NHS Lothian
Study Director:	David E Newby, MBChB PhD	University of Edinburgh / NHS Lothian

More Information

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Study Description Study Design Groups and Cohorts Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Jenkins WS, Vesey AT, Stirrat C, Connell M, Lucatelli C, Neale A, Moles C, Vickers A, Fletcher A, Pawade T, Wilson I, Rudd JH, van Beek EJ, Mirsadraee S, Dweck MR, Newby DE. Cardiac α(V)β(3) integrin expression following acute myocardial infarction in humans. Heart. 2017 Apr;103(8):607-615. doi: 10.1136/heartjnl-2016-310115. Epub 2016 Dec 7.

Responsible Party:	University of Edinburgh
ClinicalTrials.gov Identifier:	NCT01813045 History of Changes
Other Study ID Numbers:	2012/R/CAR/22; FS/12/84/29814 ( Other Grant/Funding Number: BHF Clinical Research Training Fellowship )
First Posted:	March 18, 2013
Last Update Posted:	August 30, 2016
Last Verified:	March 2015

Keywords provided by University of Edinburgh:

Angiogenesis; Fibrosis; Myocardial Infarction; Imaging	CT-PET; PET-CT; Cardiac MRI

Additional relevant MeSH terms:

Fibrosis; Infarction; Myocardial Infarction; Neovascularization, Pathologic; Pathologic Processes; Ischemia	Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Metaplasia