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

Diabetes Mellitus Clinical Trial

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

Status Completed

Clinical Trial 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.

Clinical Trial Description

Randomization and double-blind study treatment period to either placebo or LDM (1:1) of willing and eligible patients will occur at the end of the open label run-in phase per the parent CIRT protocol, and will be stratified by time since the qualifying event (< 6 or ≥ 6 months from the date of MI or most recent angiogram), type of event (MI or multivessel CAD), presence of either type 2 DM or metabolic syndrome, and site, which will ensure balance in the proposed study. Patients willing to participate in CIRT will be asked to enroll into the sub-study and may sign the CIRT-CFR informed consent at any point between signing the parent CIRT informed consent and completing the parent CIRT randomization visit (Visit 4). After giving informed consent for the ancillary CIRT-CFR, patients will undergo the baseline PET scan along with echocardiography at any point between the parent CIRT post run-in visit (Visit 3) and up to 4 weeks after randomization (Visit 4).

Imaging will be performed at the 3 imaging centers (BWH, OHI, and UAB). To minimize participant and site burden, only a baseline and single follow-up imaging time point will be pursued. Imaging tests (PET and echo) will be scheduled on the same day for patient convenience if possible, and no more than one week apart. "Baseline" study visit imaging will follow the open label run-in period of the parent trial to enhance long-term compliance and eliminate risk of radiation exposure for any individuals with immediate intolerance to the LDM study protocol. The imaging tests proposed are non-invasive, routinely performed, and historically well tolerated by patients. ;

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• Coronary Heart Disease
• Diabetes Mellitus
• Heart Diseases
• Inflammation
• Metabolic Syndrome
• Myocardial Ischemia

• NCT number: NCT02786134
• Study type: Interventional
• Source: Brigham and Women's Hospital
• Status: Completed
• Phase: N/A
• Start date: April 2016
• Completion date: October 2019