COLCOT-T2D CLINICAL TRIAL
Objective
The primary objectives of the study are:
- To evaluate whether low-dose colchicine (0.5 mg once daily) in addition to standard treatment is effective in reducing the risk of cardiovascular events in adults with type 2 diabetes but without known cardiovascular disease.
- To evaluate whether low-dose (40 mg) non-enteric aspirin given twice daily in addition to standard care is effective in reducing the risk of cardiovascular events in adults with type 2 diabetes but without known cardiovascular disease.
Key eligibility criteria for the study
1. Having type 2 diabetes
2. Being between 55 and 80 years of age
3. Having no known history of cardiovascular disease
Prevention of heart disease in people with type 2 diabetes
Background
Cardiovascular disease is the leading cause of death and disability worldwide.
People with type 2 diabetes are 2 to 3 times more likely to develop cardiovascular disease than people without diabetes. Inflammation seems to play an important role, both in the mechanisms related to diabetes and in atherosclerosis (a top cause of cardiovascular disease).
Colchicine is a medicine extracted from Colchicum autumnale (see photo). It is well known and already used in thousands of patients worldwide to treat inflammatory diseases, including gout and familial Mediterranean fever.
Colchicum autumnale
In the “COLchicine Cardiovascular Outcomes Trial (COLCOT-1)”, a 4,745-patient study that compared colchicine to a placebo as an adjunct to standard therapy for the prevention of cardiovascular events in patients with recent myocardial infarction (MI), researchers demonstrated that patients who received low-dose colchicine had significantly lower rates of cardiovascular events than those who received the placebo.
Recently, Health Canada approved the use of colchicine for the reduction of atherothrombotic events (blood clots) in adult patients with coronary artery disease, in addition to standard treatment.
Aspirin is often used to prevent blood clots in patients with cardiovascular disease. On the other hand, people with diabetes are sometimes resistant to the positive effects of aspirin in preventing cardiovascular disease. In the major clinical trials on the use of aspirin in the primary prevention of cardiovascular disease, this drug was taken once a day and had a so-called enteric coating (tablet coating to resist the acidic condition in the stomach). Some studies have suggested that diabetic patients respond better to aspirin (less resistance to the effects of aspirin) when it is taken twice a day and is uncoated.
As aspirin is an inexpensive and readily available drug, it is important to re-evaluate its dosage (times it is taken per day) and formulation (without enteric coating) in the prevention of cardiovascular disease in patients with diabetes.
Description of the clinical study
COLCOT-T2D is a clinical study conducted by the Montreal Heart Institute and funded by the Canadian Institutes of Health Research (CIHR), the Quebec government and the Montreal Heart Institute Foundation. A total of 10,000 people with type 2 diabetes who have never had documented cases of cardiovascular disease and meet the eligibility criteria will participate in the study. Participants will be randomly assigned to one of 6 groups: colchicine + aspirin, colchicine + aspirin placebo, colchicine placebo + aspirin or double placebo as well as colchicine alone or colchicine placebo alone for those not eligible for aspirin treatment. Neither the research team nor the participant will know which treatment the participant has been assigned to.
The expected duration of individual participation in this research project is estimated to be between 36 and 54 months. The duration will depend on when the participant is included in the research project and when the study ends.
All study meetings will be carried out remotely via video or telephone contact with members of the research team.
Here, in brief, are the main points of participant involvement. Additional responsibilities will be explained in detail when you register for the study.
- Initial Virtual Appointment, also known as a selection/randomization appointment.
- Virtual follow-up appointment within 7 days of the initial appointment to confirm that you have received your medication and that you have all the instructions to start taking it.
- Daily intake of colchicine and aspirin or the respective placebo.
- Appointments by video or telephone with a member of the research team every 6 months.
- End of study virtual appointment.
- Safety follow-up virtual appointment approximately 2 weeks after the end of study appointment.
This study is accompanied by two precision medicine sub-studies (pharmacogenomic study and optional proteomic study. They are not mandatory for participation in the main study described above. These sub-studies will be explained to you in detail if you are interested in participating.
In summary, the objective of the pharmacogenomic study is to assess whether there is an association between genetic biomarkers (DNA collected from saliva) and type 2 diabetes and to assess whether genetic biomarkers can predict drug response. DNA analysis can sometimes explain why people with the same disease react differently to the same drug.
The purpose of the proteomic sub-study is to assess whether there is an association between blood proteins and type 2 diabetes and to evaluate whether circulating levels of these proteins can predict drug response. Researchers will also look at the levels of drug metabolites in your blood to better understand drug response.