PROFILE-MI - The FAPI Fibrosis Study

PROline and FapI With Late Gadolinium Enhancement in Myocardial Infarction PROFILE-MI - The FAPI Fibrosis Study

The investigators here propose to investigate the timing and pattern of myocardial fibrosis activity following acute myocardial infarction using hybrid 68Ga-FAPI positron emission tomography and cardiovascular magnetic resonance. The investigators hypothesise that peak fibrosis activity will occur within 2-4 weeks of acute myocardial infarction and will predict subsequent scar formation and cardiac remodelling. Simultaneously, matrix remodelling and fibrosis activity in aortic and coronary atheroma will be assessed enabling the exploration of the presence of unstable atheroma.

Study Overview

• Status: Completed
• Conditions: Myocardial Infarction; Myocardial Fibrosis
• Intervention / Treatment: Radiation: 68Gallium FAPI PET/MR scan

Detailed Description

Fibrosis is a fundamental process underlying almost all cardiomyopathic conditions. Established fibrosis can be detected by existing imaging techniques including cardiovascular magnetic resonance. However, these techniques are not specific for fibrosis and do not directly measure fibrosis activity or matrix remodelling. This limits the ability to detect early disease and differentiate active from end-stage phenotypes. Fibroblast activation protein is a key factor in fibrogenesis that is expressed in the myocardium following myocardial infarction and in thin-capped fibroatheroma. Radiolabelled fibroblast activation protein inhibitor (68Ga-FAPI) measures in vivo fibrosis activity and matrix remodelling, as supported by preliminary pilot studies. The timing and pattern of myocardial fibrosis activity following acute myocardial infarction will be investigated using hybrid 68Ga-FAPI positron emission tomography. The investigators hypothesise that peak fibrosis activity will occur within 2-4 weeks of acute myocardial infarction and will predict subsequent scar formation and cardiac remodelling. Simultaneously, matrix remodelling and fibrosis activity in aortic and coronary atheroma will also be assessed allowing exploration of the presence of unstable atheroma. This project will enhance understanding of fibrosis activity and matrix remodelling in myocardial infarction and unstable atherosclerotic plaque with potential future application to a broad range of cardiovascular diseases.

• Study Type: Observational
• Enrollment (Actual): 80

Contacts and Locations

Study Locations

• United Kingdom
  • City Of Edinburgh
    • Edinburgh, City Of Edinburgh, United Kingdom, EH16 4SA
      • Royal Infirmary of Edinburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy volunteer participants (cohort 1, n=20): those without significant or serious comordibity or known cardiac disease

Participants with acute myocardial infarction (cohorts 2 and 3, n=40): ST-elevation myocardial infarction within 3 weeks of enrollment

Participants with chronic myocardial infarction (n=20): ST-elevation myocardial infarction 24 months or more prior to enrollment

Description

Inclusion Criteria:

• specific to cohort;
• aged 50 years or older

Exclusion Criteria:

• Claustrophobia
• Inability to undergo MRI
• eGFR <30ml/min/1.73^m2

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Healthy volunteers; Age- and sex- matched to participants, those aged 50 or over without known heart disease. n=20	Radiation: 68Gallium FAPI PET/MR scan; 68Gallium FAPI PET/MR scan
Acute myocardial infarction - multi-timepoint imaging; Those aged 50 or over with recent myocardial infarction who will be imaged using PET/MR at 1,2,4, and 12 weeks post-MI. n=20	Radiation: 68Gallium FAPI PET/MR scan; 68Gallium FAPI PET/MR scan
Acute or chronic myocardial infarction - single timepoint imaging; Those aged 50 or over with recent (n=20) or prior established (>24 months, n=20) myocardial infarction who will be imaged at a single timepoint (1,2,4, or 12 weeks post-MI for acute, at the time of enrolement to the study for chronic).	Radiation: 68Gallium FAPI PET/MR scan; 68Gallium FAPI PET/MR scan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time of maximal fibrosis activity following myocardial infarction	SUVmax and TBR of 68Ga-FAPI uptake within the infarct, border zone, and remote myocardium	12 weeks
Whether fibrosis activity predicts myocardial scar volume and ventricular remodelling	As measured by CMR 12 months following acute MI	12 months
Fibrosis activity and myocardial remodelling within atherosclerotic plaque in patients with myocardial infarct	SUVmax and TBR of 68Ga-FAPI uptake within areas of atherosclerotic plaque in the aorta and/or carotid arteries	12 weeks

Collaborators and Investigators

• Sponsor: University of Edinburgh

Study record dates

Study Major Dates

• Study Start (Actual): April 21, 2021
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): December 31, 2023

Study Registration Dates

• First Submitted: April 26, 2022
• First Submitted That Met QC Criteria: April 26, 2022
• First Posted (Actual): May 2, 2022

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 16, 2024
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Myocardial Infarction; Infarction; Fibrosis
• Other Study ID Numbers: 262477; E202251 (Other Identifier: University of Edinburgh)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No