COLPET: Colchicine in Vascular Inflammation Assessed With PET Imaging

Sponsor

Montreal Heart Institute (Other)

Overall Status

Completed

CT.gov ID

NCT02162303

Collaborator

(none)

106

Enrollment

Location

Arms

Duration (Months)

5.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Atherosclerotic Vascular Disease	Drug: Colchicine Drug: Placebo	Phase 2

Detailed Description

This is an interventional trial targetting patients 18 years old or older with a carotid artery or an ascending aorta to background ration (TBR) of ≥1.6 as determined by 18 fluorodeoxyglucose (18F-FDG) uptake measured by positron emission tomography (PET) as evidence of atherosclerotic plaque inflammation.

Following randomization,patients will be followed over a period of 6 months (24 weeks), through 2 phone contacts at 6 and 20 weeks and 2 on-site visits at 12 and 24 weeks.

Each on-site visits will include blood draws to monitor routine chemistry and hematology,as well as biomarkers and lipid profiles.

Each phone contacts will include monitoring of patient's general health and well-being.

PET imaging will be performed at baseline and at the 24-weeks visit.

Safety in this study will be assessed by clinical laboratory parameters, physical examinations, ECGs, vital signs, and the frequency and intensity of clinical adverse events (AEs).

The Montreal Health Innovations Coordinating Center (MHICC) will be responsible for processing and quality control of the data. Project management will be carried out as described in the MHICC standard operating procedures (SOPs) for clinical studies. The handling of data, including data quality control, will comply with all applicable regulatory guidelines, MHICC SOPs and the study Data Management Plan. As such, a MHICC medical monitor will be appointed to the trial as the serious adverse event reporting contact (24/7).

Study Design

Study Type:

Interventional

Actual Enrollment :

106 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Supportive Care

Official Title:

A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Effects of Colchicine on Vascular Inflammation as Assessed With Position Emission Tomography (PET) Imaging in Patients With Atherosclerotic Vascular Disease (COLPET)

Study Start Date :

May 1, 2014

Actual Primary Completion Date :

Jul 1, 2015

Actual Study Completion Date :

Jan 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Colchicine Colchicine 0.6 mg tablets,once daily, for 6 months	Drug: Colchicine 0.6 mg a day of active treatment or placebo for 24 weeks Other Names: Colchicum autumnale
Placebo Comparator: Placebo Sugar,given once daily, over 6 months.To mimic active treatment.	Drug: Placebo Sugar,given once daily, over 6 months.To mimic active treatment Other Names: Sugar

Arm

Intervention/Treatment

Experimental: Colchicine

Colchicine 0.6 mg tablets,once daily, for 6 months

Drug: Colchicine

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

Other Names:

Colchicum autumnale

Placebo Comparator: Placebo

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

Drug: Placebo

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

Other Names:

Sugar

Outcome Measures

Primary Outcome Measures

Change in the average of maximum target-to-background (TBR) values (Mean MAX TBR) of the ascending aorta [baseline and 6 months]

Secondary Outcome Measures

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]
MDS TBR is defined as the 1.5 cm segment that demonstrates the highest PET/CT activity at baseline and is calculated as the Mean Max TBR values derived from approximately 5 contiguous axial segments.
Change in soluble biomarkers of inflammation [baseline and 6 months]
Soluble biomarkers of inflammation include high sensitivity C-Reactive Protein (hs-CRP). As well, frozen samples (whole blood, plasma and leucocytes for RNA analyses) will be kept for future use for evaluation of biomarkers related to cardiovascular disease and responses to the treatment mostly regarding: lipid, inflammation and oxidative stress.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

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
Other indications for colchicine use (mainly chronic indications represented by Familial Mediterranean Fever or gout)
History of an allergic reaction or significant sensitivity to constituents of study drug
Use of an investigational chemical agent less than 50 days or 5 half-lives prior to baseline (whichever is longer)
Judged by the investigator to be an unsuitable candidate for the study