Angiogenesis and Fibrosis in Myocardial Infarction

This study is not yet open for participant recruitment. (see Contacts and Locations)
Verified March 2013 by University of Edinburgh
Sponsor:
Information provided by (Responsible Party):
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT01813045
First received: March 14, 2013
Last updated: March 15, 2013
Last verified: March 2013
  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:


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.


Estimated Enrollment: 40
Study Start Date: April 2013
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2015 (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.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   40 Years and older
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

Contacts
Contact: William SA Jenkins, MBChB 01312421000 ext 26428 williamjenkins@doctors.net.uk
Contact: David E Newby, MBChB PhD 01312421000 d.e.newby@nhs.net

Locations
United Kingdom
University of Edinburgh Not yet recruiting
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

No publications provided

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: March 15, 2013
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
Cardiovascular Diseases
Heart Diseases
Ischemia
Metaplasia
Myocardial Ischemia
Necrosis
Pathologic Processes
Vascular Diseases

ClinicalTrials.gov processed this record on October 30, 2014