RecruitingPhase 3NCT04181996

Canadian Study of Arterial Inflammation in Patients With Diabetes and Vascular Events: EvaluatioN of Colchicine

The Canadian Study of Arterial Inflammation in Patients With Diabetes and Recent Vascular Events: EvaluatioN of Colchicine Effectiveness (CADENCE)

Sponsor

Ottawa Heart Institute Research Corporation

Enrollment

115 participants

Start Date

Aug 1, 2020

Study Type

INTERVENTIONAL

Conditions

Cardiovascular Diseases Diabetes Atherosclerosis Inflammation

Summary

Cardiovascular Disease (CVD) is a leading cause of death in the developed world. Atherosclerosis causes plaques in the blood vessels and is a common form of CVD. Inflammation is now recognized as a major cause of atherosclerosis. Therapies that target inflammation are being examined as a potential treatment option. Imaging to detect inflammation may be a solution to understand mechanisms and to optimize patient selection and outcomes for these drugs. Fluorodeoxyglucose (FDG) PET imaging can detect inflammation in the plaque and identify patients vulnerable to plaque rupture which cause events such as myocardial infarctions (MI) and strokes. The primary objective of this proposal(CADENCE) is to determine if the drug colchicine has an effect on plaque inflammation in patients at high risk for events (patients with diabetes or pre-diabetes and recent myocardial infarction, stroke or transient ischemic attacks (TIAs)). This mechanistic and proof-of-concept study will set the stage for future studies that will determine if inflammation imaging can be integrated into clinical practice to personalize decisions for anti-inflammation therapies.

Eligibility

Min Age: 18 Years

Inclusion Criteria6

Patients who have:
Type 2 Diabetes (on diet, oral hypo-glycemic agents and/or insulin) or pre-diabetes (defined by Diabetes Canada as HbA1C=6.0-6.45% or increased fasting blood sugar (FBS) (6.1-6.9 mmol/L) or impaired glucose tolerance);
suffered a recent cardiovascular event (≤120 days post ACS (i.e. STEMI or nonSTEMI) or TIA/stroke with associated large vessel atherosclerotic disease confirmed on US, CT or MRI;
stable symptoms and hemodynamics;
age ≥18 years;
given informed consent. Standard definitions will be used for STEMI, NSTEMI, and for ischemic stroke confirmed by CT or MRI and TIA confirmed by a neurologist.

Exclusion Criteria23

Patients who have
planned revascularization of infarct or stroke related artery more than 120 days after the qualifying/index event;
a recent CV event likely to have been embolic in the opinion of the neurologist or cardiologist;
recent CV event likely to have been secondary to myocardial infarction with non-obstructive coronary arteries (MINOCA) in the opinion of the cardiologist;
severe LV dysfunction (EF<30%);
severe valve disease requiring intervention;
decompensated heart failure;
active infection (e.g. pneumonia, active skin infections, and on antibiotics);
chronic diarrhea;
immune compromise (e.g. recurrent infection);
history of cancer within the last 3 years (other than a successfully treated cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix).
active inflammatory conditions (e.g. rheumatoid arthritis, chronic inflammatory bowel disease, SLE, systemic anti-inflammatory therapy (e.g. prednisone, methotrexate));
pregnancy (all women of child bearing potential will have a negative BHCG test;
breastfeeding;
Women of childbearing potential who refuse to use two forms of contraception (this includes at least one form of highly effective and one effective method of contraception) throughout the study OR men capable of fathering a child who refuse to use contraception.
glomerular filtration rate (GFR) <50 ml/min/1.72m2
Use of potent p-glycoprotein inhibitors (i.e. systemic cyclosporine, clarithromycin, or systemic ketoconazole) or a strong CYP3A4 inhibitor (i.e. ritonavir, clarithromycin, or systemic ketoconazole);
Hemoglobin < 105(women) <110 (men) g/L; WBC < 3.0x 10(9)/L, platelet count< 110x 10(9)/L;
Patient with a history of cirrhosis, chronic active hepatitis or severe hepatic disease or with alanine aminotransferase (ALT) levels greater than 3 times the upper limit of normal.
unable to give informed consent;
TIA/Stroke patients with atrial fibrillation
Exclusion for CTA portion of the protocol:
Patients with dye allergy or those with GRF <60 will not undergo CTA but will have PET/CT.