Angiogenesis and Fibrosis in Myocardial Infarction - Full Text View

Purpose

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	Intervention
Myocardial Infarction Fibrosis Neovascularization, Pathologic	Procedure: Cardiac MRI scan Radiation: CT-PET scan Radiation: CT-coronary angiogram


Study Type:	Observational
Study Design:	Observational Model: Cohort Time Perspective: Prospective
Official Title:	The Identification of In Vivo Angiogenesis and Fibrosis in Myocardial Infarction Using Positron Emission Tomography.

Resource links provided by NLM:

MedlinePlus related topics: Heart Attack Nuclear Scans

U.S. FDA Resources

Further study details as provided by University of Edinburgh:

Primary Outcome Measures:

The primary outcome is heart function determined by ejection fraction (in %) 6 months following a heart attack. [ Time Frame: 6 - 12 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

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 ] [ Designated as safety issue: No ]

Biospecimen Retention: Samples Without DNA

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


Enrollment:	30
Study Start Date:	April 2013
Study Completion Date:	March 2016
Primary Completion Date:	March 2016 (Final data collection date for primary outcome measure)

Groups/Cohorts	Assigned Interventions
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.

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Eligibility


Ages Eligible for Study:	40 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01813045

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


Responsible Party:	University of Edinburgh
ClinicalTrials.gov Identifier:	NCT01813045 History of Changes
Other Study ID Numbers:	2012/R/CAR/22 FS/12/84/29814
Study First Received:	March 14, 2013
Last Updated:	August 29, 2016
Health Authority:	United Kingdom: Research Ethics Committee

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

ClinicalTrials.gov processed this record on September 29, 2016