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

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ClinicalTrials.gov Identifier: NCT04181996
Recruitment Status : Not yet recruiting
First Posted : December 2, 2019
Last Update Posted : March 4, 2020
Sponsor:
Collaborator:
Canadian Institutes of Health Research (CIHR)
Information provided by (Responsible Party):
Ottawa Heart Institute Research Corporation

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.

Condition or disease Intervention/treatment Phase
Cardiovascular Diseases Atherosclerosis Inflammation Diabetes Drug: Colchicine Oral Product Drug: Placebo oral capsule Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 115 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Double-Blind Placebo controlled trial
Primary Purpose: Treatment
Official Title: The Canadian Study of Arterial Inflammation in Patients With Diabetes and Recent Vascular Events: EvaluatioN of Colchicine Effectiveness (CADENCE)
Estimated Study Start Date : April 1, 2020
Estimated Primary Completion Date : June 30, 2023
Estimated Study Completion Date : December 31, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Colchicine

Arm Intervention/treatment
Placebo Comparator: Placebo
Placebo: Sugar pill manufactured to mimic colchicine 0.6 mg capsule. Placebo to be taken once a day.
Drug: Placebo oral capsule
Patents will be randomized to receive either placebo or colchicine

Experimental: Colchicine
Colchicine: 0.6 mg colchicine capsule to be taken once a day.
Drug: Colchicine Oral Product
Patients will be randomized to receive either placebo or colchicine




Primary Outcome Measures :
  1. 6 month change in FDG uptake TBR (Tissue to Blood Ratio) in the MDS (Maxiumum Disease Segment) [ Time Frame: 6 months ]
    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.


Secondary Outcome Measures :
  1. 6 month change in FDG uptake TBR (Tissue to Blood Ratio) in the MDS of each vascular region: aorta, left and right carotid. [ Time Frame: 6 months ]
    6 month change in FDG uptake TBR (Tissue to Blood Ratio) in the MDS of each vascular region: aorta, left and right carotid.

  2. 6 month change in FDG uptake SUV (standard uptake value) in the MDS of each vascular region: aorta, left and right carotid. [ Time Frame: 6 months ]
    6 month change in FDG uptake SUV (standard uptake value) in the MDS of each vascular region: aorta, left and right carotid.

  3. Levels of high-sensitivity C-Reactive Protein (hs-CRP) (mg/ml) and its change [ Time Frame: 6 months ]
    Levels of high-sensitivity C-Reactive Protein (hs-CRP) (mg/ml) and its change

  4. Levels of Interleukin-6 (IL-6) (pg/ml) and its change. [ Time Frame: 6 months ]
    Levels of Interleukin-6 (IL-6) (pg/ml) and its change.


Other Outcome Measures:
  1. Exploratory outcomes - Plasma levels of cytokines (pg/ml) [ Time Frame: 6 months ]
    Plasma levels of other cytokines (pg/ml)

  2. Exploratory outcomes - Levels of activated monocytes [ Time Frame: 6 months ]
    Levels of activated monocytes

  3. Exploratory outcomes - plasma levels of inflammation biomarkers [ Time Frame: 6 months ]
    Plasma levels of inflammation biomarkers

  4. Exploratory outcomes - MACE [ Time Frame: 6 months ]
    MACE (multiple adverse CV events (ACS/MI, TIA, stroke, CV death))

  5. Exploratory outcomes - non CV death [ Time Frame: 6 months ]
    non-cardiovascular death



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

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): NCT04181996


Contacts
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Contact: Linda M Garrard, BScN 613-696-7000 ext 14192 lgarrard@ottawaheart.ca
Contact: Alison D James, MSc 613-696-7000 ext 10313 ajames@ottawaheart.ca

Locations
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Canada, Ontario
University of Ottawa Heart Institute
Ottawa, Ontario, Canada, K1Y 4W7
Contact: Linda M Garrard, BScN    613-696-7000 ext 14192    lgarrard@ottawaheart.ca   
Contact: Alison D James, MSc    613-696-7000 ext 10313    ajames@ottawaheart.ca   
Principal Investigator: Rob S Beanlands, MD         
Sponsors and Collaborators
Ottawa Heart Institute Research Corporation
Canadian Institutes of Health Research (CIHR)
Investigators
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Principal Investigator: Rob S Beanlands, MD Ottawa Heart Institute Research Corporation
Publications:
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Responsible Party: Ottawa Heart Institute Research Corporation
ClinicalTrials.gov Identifier: NCT04181996    
Other Study ID Numbers: REB # - 20190355-01H CRRF:1443
First Posted: December 2, 2019    Key Record Dates
Last Update Posted: March 4, 2020
Last Verified: March 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Ottawa Heart Institute Research Corporation:
Imaging, PET, inflammation, Biomarkers, Colchicine
Additional relevant MeSH terms:
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Cardiovascular Diseases
Atherosclerosis
Arteritis
Diabetes Mellitus
Inflammation
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Pathologic Processes
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Vasculitis
Colchicine
Gout Suppressants
Antirheumatic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents