Coronary Flow Reserve to Assess Cardiovascular Inflammation (CIRT-CFR)

Summary

Coronary flow reserve (CFR, calculated as the ratio of hyperemic over rest myocardial blood flow) is emerging as a powerful quantitative prognostic imaging marker of clinical cardiovascular risk. CFR provides a robust and reproducible clinical measure of the integrated hemodynamic effects of epicardial coronary artery disease (CAD), diffuse atherosclerosis, and microvascular dysfunction on myocardial tissue perfusion. Inflammation is a key mediator of this constellation of abnormalities, affecting the entire coronary vasculature, but no clinical trial to date has shown that directly reducing inflammation lowers cardiovascular event rates. As such, the recently launched Cardiovascular Inflammation Reduction Trial (CIRT) provides a unique opportunity for mechanistic investigation of the impact of anti-inflammatory therapy on changes in CFR as a reflection of coronary vascular dysfunction, which may precede clinical outcomes, particularly in patients at high-risk of events. The investigators are ideally positioned to examine the impact of inflammation on CFR, having extensive experience in both the quantitation of CFR using clinically-integrated dynamic positron emission tomography (PET) and the ability to assess its association with cardiovascular outcomes. The central hypothesis of this ancillary proposal, CIRT-CFR, is that reducing systemic inflammation using low-dose methotrexate (LDM) will, compared to placebo, quantitatively improve myocardial blood flow and coronary flow reserve as measured by PET over one year, in stable CAD patients with type 2 diabetes or metabolic syndrome enrolled in CIRT. In so doing, improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have beneficial effects on myocardial mechanics, left ventricular deformation and function and, ultimately, symptoms and prognosis.

Conditions

• Coronary Heart Disease
• Metabolic Syndrome
• Diabetes Mellitus

Interventions

RADIATION

PET scan

A cardiac PET scan will be performed at baseline (main CIRT trial randomization) and at 12-months.

RADIATION

Echocardiogram

An echocardiogram will be performed at baseline (main CIRT trial randomization) and at 12-months.

Sponsors & Collaborators

• Ottawa Heart Institute Research Corporation

  collaborator OTHER

• University of Alabama at Birmingham

  collaborator OTHER

• Brigham and Women's Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-04-30

Primary Completion

2019-10-31

Completion

2019-10-31

Countries

• United States

Study Locations