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

NCT04181996 | Completed Phase 3 DMC

• 1 other identifier: REB # - 20190355-01H CRRF:1443
• Study Type: interventional
• Target: 115
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Inflammation; Diabetes; Cardiovascular Diseases; Atherosclerosis

Keywords

Imaging, PET, inflammation, Biomarkers, Colchicine

Outcome Measures

Primary Outcomes (1)

• 6 month change in FDG uptake TBR (Tissue to Blood Ratio) in the MDS (Maximum Disease Segment)

  The primary endpoint will be the change over 6 months in the FDG uptake TBR (Tissue-to-blood ratio) as a marker of arterial plaque inflammation in the maximum disease segment (MDS)(the segment with the highest TBR at baseline) in any vasculature imaged whether it be left or right carotid or aorta.

  6 months

Secondary Outcomes (4)

• 6 month change in FDG uptake TBR (Tissue to Blood Ratio) in the MDS of each vascular region: aorta, left and right carotid.

  6 months

• 6 month change in FDG uptake SUV (standard uptake value) in the MDS of each vascular region: aorta, left and right carotid.

  6 months

• Levels of high-sensitivity C-Reactive Protein (hs-CRP) (mg/ml) and its change

  6 months

• Levels of Interleukin-6 (IL-6) (pg/ml) and its change.

  6 months

Other Outcomes (7)

• Exploratory outcomes - Plasma levels of cytokines (pg/ml)

  6 months

• Exploratory outcomes - Levels of activated monocytes

  6 months

• Exploratory outcomes - plasma levels of inflammation biomarkers

  6 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Placebo: Sugar pill manufactured to mimic colchicine 0.6 mg capsule. Placebo to be taken once a day.

Drug: Placebo oral capsule

Colchicine

EXPERIMENTAL

Colchicine: 0.6 mg colchicine capsule to be taken once a day.

Drug: Colchicine Oral Product

Interventions

Colchicine Oral Product DRUG

Patients will be randomized to receive either placebo or colchicine

Colchicine

Placebo oral capsule DRUG

Patents will be randomized to receive either placebo or colchicine

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Canadian Institutes of Health Research (CIHR): collaborator
• Ottawa Heart Institute Research Corporation: lead

Study Sites (2)

Mazankowski Alberta Heart Institute

Edmonton, Alberta, T6G 2B7, Canada

Location

University of Ottawa Heart Institute

Ottawa, Ontario, K1Y 4W7, Canada

Location

Related Publications (3)

• Nidorf SM, Eikelboom JW, Budgeon CA, Thompson PL. Low-dose colchicine for secondary prevention of cardiovascular disease. J Am Coll Cardiol. 2013 Jan 29;61(4):404-410. doi: 10.1016/j.jacc.2012.10.027. Epub 2012 Dec 19.

  PMID: 23265346 BACKGROUND

• Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, Lopez-Sendon J, Ostadal P, Koenig W, Angoulvant D, Gregoire JC, Lavoie MA, Dube MP, Rhainds D, Provencher M, Blondeau L, Orfanos A, L'Allier PL, Guertin MC, Roubille F. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019 Dec 26;381(26):2497-2505. doi: 10.1056/NEJMoa1912388. Epub 2019 Nov 16.

  PMID: 31733140 BACKGROUND

• Boczar KE, Shin S, deKemp RA, Dowlatshahi D, Tavoosi A, Wiefels C, Liu P, Lochnan H, MacPherson PA, Chong AY, Torres C, Leung E, Tawakol A, Ahmadi A, Garrard L, Lefebvre C, Kelly C, MacPhee P, Tilokee E, Raggi P, Wells GA, Beanlands R. The Canadian Study of Arterial Inflammation in Patients with Diabetes and Recent Vascular Events, Evaluation of Colchicine Effectiveness (CADENCE): protocol for a randomised, double-blind, placebo-controlled trial. BMJ Open. 2023 Nov 10;13(11):e074463. doi: 10.1136/bmjopen-2023-074463.

  PMID: 37949621 DERIVED

MeSH Terms

Conditions

Cardiovascular Diseases; Atherosclerosis; Inflammation; Diabetes Mellitus

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Kevin Boczar, MD

  Ottawa Heart Institute Research Corporation

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-Blind Placebo controlled trial
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 19, 2019
• First Posted: December 2, 2019
• Study Start: August 1, 2020
• Primary Completion: December 16, 2025
• Study Completion: December 16, 2025
• Last Updated: May 1, 2026

Record last verified: 2026-04

Locations

CA (2)