NCT01813045

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at below P25 for all trials

Timeline
Completed

Started Apr 2013

Typical duration for all trials

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

March 14, 2013

Completed
4 days until next milestone

First Posted

Study publicly available on registry

March 18, 2013

Completed
14 days until next milestone

Study Start

First participant enrolled

April 1, 2013

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2016

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2016

Completed
Last Updated

August 30, 2016

Status Verified

March 1, 2015

Enrollment Period

2.9 years

First QC Date

March 14, 2013

Last Update Submit

August 29, 2016

Conditions

Myocardial InfarctionFibrosisNeovascularization, Pathologic

Keywords

AngiogenesisFibrosisMyocardial InfarctionImagingCT-PETPET-CTCardiac MRI

Outcome Measures

Primary Outcomes (1)

  • The primary outcome is heart function determined by ejection fraction (in %) 6 months following a heart attack.

    6 - 12 months

Secondary Outcomes (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).

    1 year

Study Arms (3)

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 scanRadiation: CT-PET scanRadiation: CT-coronary angiogram

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 scanRadiation: CT-PET scanRadiation: CT-coronary angiogram

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 scanRadiation: CT-PET scanRadiation: CT-coronary angiogram

Interventions

Cardiac MRI scanPROCEDURE

Cardiac MRI scan with assessment of late gadolinium enhancement and T1 mapping.

Chronic Coronary Occlusion groupMI (non-revascularised)MI (revascularised)
CT-PET scanRADIATION

Computed Tomography / Positron Emission Tomography scan with 18F-fluciclatide tracer.

Chronic Coronary Occlusion groupMI (non-revascularised)MI (revascularised)
CT-coronary angiogramRADIATION

CT-coronary angiogram following CT-PET scan. Standard protocol.

Chronic Coronary Occlusion groupMI (non-revascularised)MI (revascularised)

Eligibility Criteria

Age40 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

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

You may qualify if:

  • 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.

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Edinburgh

Edinburgh, Lothian, EH16 4TJ, United Kingdom

Location

Related Publications (1)

  • 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 alphaVbeta3 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.

    PMID: 27927700DERIVED

Biospecimen

Retention: SAMPLES WITHOUT DNA

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

MeSH Terms

Conditions

Myocardial InfarctionFibrosisNeovascularization, Pathologic

Condition Hierarchy (Ancestors)

Myocardial IschemiaHeart DiseasesCardiovascular DiseasesVascular DiseasesInfarctionIschemiaPathologic ProcessesPathological Conditions, Signs and SymptomsNecrosisMetaplasia

Study Officials

  • William SA Jenkins, MBChB

    University of Edinburgh / NHS Lothian

    PRINCIPAL INVESTIGATOR

  • David E Newby, MBChB PhD

    University of Edinburgh / NHS Lothian

    STUDY DIRECTOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

March 14, 2013

First Posted

March 18, 2013

Study Start

April 1, 2013

Primary Completion

March 1, 2016

Study Completion

March 1, 2016

Last Updated

August 30, 2016

Record last verified: 2015-03

Locations

GB(1)