Cardiovascular Inflammation Reduction Trial - Inflammation Imaging Study (CIRT)
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|ClinicalTrials.gov Identifier: NCT02576067|
Recruitment Status : Completed
First Posted : October 15, 2015
Results First Posted : April 20, 2020
Last Update Posted : April 20, 2020
Vascular inflammation, a central feature of atherosclerosis, participates in the initiation, perpetuation and instability of plaques. Multiple clinical trials of cholesterol lowering therapy with statins have demonstrated that reductions in atherosclerotic cardiovascular disease (CVD) events are associated with reductions in both LDL cholesterol (LDL-C) and the systemic inflammatory mediator C-reactive protein (CRP). The Cardiovascular Inflammation Reduction Trial (CIRT) investigates if an anti-inflammatory agent commonly used in rheumatoid arthritis (low dose methotrexate (LDM)) can reduce CV morbidity and mortality among patients with a prior myocardial infarction or angiographically demonstrated multivessel coronary artery disease (GCO#13-1467).
In this ancillary CIRT imaging study, the investigators propose to use this well validated approach by non-invasive serial FDG-PET/CT imaging in a subset of patients enrolled in the main CIRT trial to directly visualize vascular inflammation. Once the subjects are enrolled in the main CIRT trial, baseline imaging will be done and follow up imaging will be done approximately 8 months after the baseline imaging.
18FDG-PET imaging data will be acquired, analyzed centrally and results incorporated into the main CIRT database. The investigators hypothesize that LDM treatment will result in a significant decrease in plaque inflammation as measured by 18-FDG-PET/CT after 8 months as compared to placebo.
|Condition or disease||Intervention/treatment||Phase|
|Vascular Inflammation Atherosclerotic Cardiovascular Disease||Drug: Low dose methotrexate Drug: Placebo||Phase 3|
The NHLBI funded (Ridker 5U01HL101422) Cardiovascular Inflammation Reduction Trial (CIRT) provides a unique opportunity to investigate whether a commonly used anti-inflammatory agent used in rheumatoid arthritis (low dose methotrexate (LDM)) can reduce CVD morbidity and mortality among patients with stable coronary artery disease. CIRT, is a randomized, double-blind, placebo-controlled, multi-center trial among 7,000 men and women with prior myocardial infarction or angiographically demonstrated multivessel coronary artery disease. Eligible participants will be randomly allocated over a three to four year period to usual care plus placebo or usual care plus LDM (average dose of 15-20 mg po/weekly. CIRT proposes that the reduction in CVD events with methotrexate derives from its effect on vascular inflammation, thus it is crucial to incorporate a measure of vascular inflammation imaging for confirmation of the primary mechanism of action underlying CIRT. As such, the direct evaluation of arterial inflammation would enhance the scientific value of the CIRT trial.
The inclusion of the proposed vascular inflammation imaging substudy has widespread implications that will allow this imaging modality to serve as a surrogate measure of disease, and thereby provide an opportunity for stratification in individuals at risk for CVD and evaluation of other interventions with presumed anti-inflammatory effects.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||123 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Cardiovascular Inflammation Reduction Trial (CIRT) - Inflammation Imaging Study|
|Actual Study Start Date :||December 18, 2015|
|Actual Primary Completion Date :||March 29, 2019|
|Actual Study Completion Date :||March 29, 2019|
Experimental: Low dose methotrexate
average dose of 15-20 mg po/weekly
Drug: Low dose methotrexate
Study participants will additionally receive 1 mg daily oral folate.
Placebo Comparator: Placebo
- Change in Arterial Inflammation [ Time Frame: baseline and 8 months ]Change in arterial inflammation - The relative change at 8 months as compared to baseline in arterial inflammation as measured by the most diseased segment (MDS) of the index vessel. The MDS is defined as the 1.5 cm segment within the carotid artery (right or left carotid) that demonstrates the highest PET/CT activity, and is calculated as a mean of maximum TBR values derived from 3 contiguous axial segments. The index vessel in turn is defined as the vessel (either aorta, right, or left carotid) with the greatest mean TBR at baseline. (MDS TBR Index Vessel)
- Change in Max Target-to-background (TBR) [ Time Frame: baseline and 8 months ]Change in max target-to-background (TBR) - The mean of max TBR within the carotid arteries as an average of the slices from the left and right carotid) at follow up imaging as compared to baseline.
- Change in Max TBR Within the Carotid Arteries [ Time Frame: baseline and 8 months ]Change in max target-to-background (TBR) - The mean of max TBR within the carotid arteries as an average of the slices from the left and right carotid)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02576067
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02199|
|United States, New York|
|Icahn School of Medicine at Mount Sinai|
|New York, New York, United States, 10029|
|St. Michael's Hospital|
|Toronto, Ontario, Canada|
|Principal Investigator:||Zahi Fayad, PhD||Icahn School of Medicine at Mount Sinai|