Colchicine in Vascular Inflammation Assessed With PET Imaging

NCT02162303 | Completed Phase 2 DMC

• 1 other identifier: MHIPS-002
• Study Type: interventional
• Target: 106
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this trial is to assess the effects of colchicine on vascular inflammation measured by (FDG)-PET imaging in patients with atherosclerotic vascular disease. This effect will also be measured by soluble plasma biomarkers. Finally, an optional pharmacogenomic investigation will be performed to identify genetic biomarkers of patient response.

Conditions

Atherosclerotic Vascular Disease

Keywords

Atherosclerosis; Vascular; Cardiovascular; Coronary artery disease; Imaging; PET; Scan; anti-inflammatory

Outcome Measures

Primary Outcomes (1)

• Change in the average of maximum target-to-background (TBR) values (Mean MAX TBR) of the ascending aorta

  baseline and 6 months

Secondary Outcomes (4)

• Change in the Mean Maximum Target-to-background (Mean MAX TBR) of carotid arteries

  baseline and 6 months

• Change in the average of the mean TBR values (Mean MEAN TBR)

  baseline and 6 months

• Change in the Most Diseased Segment TBR values (MDS TBR) in the carotid arteries and ascending aorta

  baseline and 6 months

• Change in soluble biomarkers of inflammation

  baseline and 6 months

Study Arms (2)

Colchicine

EXPERIMENTAL

Colchicine 0.6 mg tablets,once daily, for 6 months

Drug: Colchicine

Placebo

PLACEBO COMPARATOR

Sugar,given once daily, over 6 months.To mimic active treatment.

Drug: Placebo

Interventions

Colchicine DRUG

0.6 mg a day of active treatment or placebo for 24 weeks

Also known as: Colchicum autumnale

Colchicine

Placebo DRUG

Sugar,given once daily, over 6 months.To mimic active treatment

Also known as: Sugar

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female patients providing informed consent
• Patient must have evidence of coronary artery disease (CAD) as evidenced by at least one of the following:
• Angiographic evidence of at least 50% stenosis in one coronary artery (except for left main coronary artery stenosis, in which 30% is acceptable)
• History of prior percutaneous coronary intervention (PCI)
• History of prior acute coronary syndrome (ACS) event (ST elevation myocardial infarction (STEMI), non-STEMI or unstable angina)
• Patient has a carotid or ascending aorta atherosclerotic plaque inflammation TBR of 1.6 or more as determined by 18F-FDG uptake measured by PET scanning
• Patient must be on a stable dose for at least 8 weeks before baseline if taking medications used to control angina, hypertension, serum lipids (including statins) or any medication that can have an effect on inflammation
• Female patient is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or is of childbearing potential and practices a birth control method throughout the study and for 30 days after study completion
• Patient is judged to be in good general health as determined by the principal investigator
• Patient must be able and willing to comply with the requirements of this study protocol

You may not qualify if:

• Poorly controlled medical condition, such as uncontrolled diabetes, documented history of recurrent infections, unstable ischemic heart disease, congestive heart failure, a left ventricular ejection fraction of less than 40%, recent stroke (within the past 3 months), chronic leg ulcer or any other condition which, in the opinion of the investigator, would put the patient at risk if participating in the study
• History of ACS, PCI, myocardial infarction, carotid revascularization or hospitalization for a cardiac condition within 12 weeks of baseline
• Prior coronary artery bypass graft
• Planned change in medical treatment during the study, that can have effect on inflammation, for angina, serum lipids, and other conditions
• History of cancer or lymphoproliferative disease other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and/or localized carcinoma in situ of the cervix
• History of listeriosis, treated or untreated tuberculosis, persistent chronic infections, or recent active infections requiring hospitalization or treatment with intravenous anti-infective agent within 30 days or oral anti-infective agent within 14 days prior to baseline
• Hepatitis B or hepatitis C viral infection
• Inflammatory bowel disease (Crohn's disease or ulcerative colitis) or patient with chronic diarrhea
• Pre-existent progressive neuromuscular disease or patient with creatine phosphokinase (CPK) level \> 3 times the upper limit of normal at baseline
• Current use or plans to use anti-retroviral therapy at any time during the study, or with active chronic disease often treated with a protease inhibitor, including AIDS
• Diagnosed with immune deficiency or as immunocompromised
• Any of the following: hemoglobin \< 120g/L, white blood cell count \< 3.0 X 109/L, platelet count \<130 X 109/L, Alanine aminotransferase (ALT) \> 3 times the upper limit of normal, Aspartate aminotransferase (AST) \> 3 times the upper normal limit, total bilirubin \> 2 times the upper normal limit, creatinine \> 150 umol/L, creatinine clearance \< 30 mL/min, or history of cirrhosis or severe hepatic disease
• Pregnant or breast-feeding or considering becoming pregnant during the study or for 6 months after the last dose of study medication
• History of clinically significant drug or alcohol abuse in the last year
• Previous bilateral carotid surgery

Sponsors & Collaborators

• Montreal Heart Institute: lead

Study Sites (1)

Montreal Heart Institute

Montreal, Quebec, H1T 1C8, Canada

Location

MeSH Terms

Conditions

Atherosclerosis; Coronary Artery Disease

Interventions

Colchicine; Sugars

Condition Hierarchy (Ancestors)

Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Coronary Disease; Myocardial Ischemia; Heart Diseases

Intervention Hierarchy (Ancestors)

Alkaloids; Heterocyclic Compounds; Carbohydrates

Study Officials

• Jean-Claude Tardif, MD

  Montreal Heart Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2014
• First Posted: June 12, 2014
• Study Start: May 1, 2014
• Primary Completion: July 1, 2015
• Study Completion: January 1, 2016
• Last Updated: February 21, 2020

Record last verified: 2020-02

Locations

CA (1)