Overview

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

Status:
Recruiting
Trial end date:
2023-12-31
Target enrollment:
0
Participant gender:
All
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.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Ottawa Heart Institute Research Corporation
Collaborator:
Canadian Institutes of Health Research (CIHR)
Treatments:
Colchicine
Criteria
Inclusion Criteria:

Patients who have:

1. 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);

2. suffered a recent cardiovascular event (30-90 days post ACS (i.e. STEMI or nonSTEMI)
or TIA/stroke with ipsilateral large vessel atherosclerotic disease confirmed on US,
CT or MRI;

3. stable symptoms and hemodynamics;

4. age ≥18 years;

5. 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 Criteria:

Patients who have

1. planned revascularization of infarct or stroke related artery;

2. severe uncontrolled diabetes (FBS >11.1 mmol/L or HbA1C >9.0% who require aggressive
diabetes management);

3. a recent CV event likely to have been embolic in the opinion of the neurologist or
cardiologist;

4. severe LV dysfunction (EF<30%);

5. severe valve disease requiring intervention;

6. decompensated heart failure;

7. active infection;

8. immune compromise (e.g. recurrent infection; chronic inflammatory bowel disease;
systemic anti-inflammatory therapy; past cancer);

9. pregnancy or breastfeeding;

10. unable to give informed consent;

11. contrast allergy (will not have CTA but may have PET/CT without CTA);

12. glomerular filtration rate (GFR) <50 ml/min/1.72m2

13. Use of p-glycoprotein inhibitor (e.g. cyclosporine, verapamil, or quinidine) or a
strong CYP3A4 inhibitor (e.g. ritonavir, clarithromycin, or ketoconazole);

14. Hemoglobin < 105(women) <110 (men) g/L; WBC < 3.0x 10(9)/L, platelet count< 110x
10(9)/L;

15. 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.