Objective
The REC1TE trial tests anti-inflammatory therapy with tablet 0.5 mg colchicine taken once daily as compared with placebo and added to existing medical therapy, including insulin therapy, in persons with established type 1 diabetes and with chronic inflammation and who are at high risk of cardiovascular disease or already have cardiovascular disease.
The primary objective of the trial is to evaluate how colchicine influences biomarkers related to risk of cardiovascular disease and inflammation. This is done to assess if colchicine may potentially reduce risk of cardiovascular events such as heart attack or stroke in type 1 diabetes.
Secondary objectives include evaluating if colchicine may safely be added to insulin therapy in type 1 diabetes and to assess how colchicine influences insulin therapy, for example by potential changes in insulin dosage, body weight and risk of hypoglycemia and risk of diabetic ketoacidosis.
Finally, the REC1TE trial also investigates how colchicine influences metabolism in type 1 diabetes, for example how colchicine influences body composition and lean muscle mass and fat mass.
Background Rationale
Fifty million people world-wide have type 1 diabetes, and their average life expectancy is reduced by more than a decade due to cardiovascular disease as compared with people without diabetes. The naturally occurring bodily process of inflammation normally combats infection, but chronic inflammation may arise in some individuals and this is critical in driving the progression of cardiovascular disease. During recent years the concept of residual inflammatory risk has emerged a novel cardiovascular risk factor like high blood pressure or high cholesterol levels. The anti-inflammatory drug colchicine (used for many years for the treatment of gout) has recently been approved for the treatment of residual inflammatory risk and atherosclerotic cardiovascular disease by Health Canada. Colchicine was also recently recommended in international treatment guidelines for lowering risk of cardiovascular events like heart attack or stroke in persons with pre-existent atherosclerotic cardiovascular disease. The evidence base is solid for the observed cardiovascular benefits with colchicine, but persons with type 1 diabetes are rarely included in the large cardiovascular outcome trials that provide the data for this. Therefore, if colchicine treatment may also reduce risk of cardiovascular events in type 1 diabetes is unknown.
Description of Project
Fifty million people world-wide have type 1 diabetes, and their average life expectancy is reduced by more than a decade due to cardiovascular disease as compared with people without diabetes. The naturally occurring bodily process of inflammation normally combats infection, but chronic inflammation may arise in some individuals and this is critical in driving the progression of cardiovascular disease. During recent years the concept of residual inflammatory risk has emerged as a novel cardiovascular risk factor like high blood pressure or high cholesterol levels. The anti-inflammatory drug colchicine (used for many years for the treatment of gout) has recently been approved for the treatment of residual inflammatory risk and atherosclerotic cardiovascular disease by Health Canada. Colchicine was also recently recommended in international treatment guidelines for lowering risk of cardiovascular events like heart attack or stroke in persons with pre-existent atherosclerotic cardiovascular disease. The evidence base is solid for the observed cardiovascular benefits with colchicine, but persons with type 1 diabetes are rarely included in the large cardiovascular outcome trials that provide the data for this. Therefore, if colchicine treatment may also reduce risk of cardiovascular events in type 1 diabetes is unknown.
The REC1TE trial is a randomized clinical trial that aims to evaluate the influence and safety of colchicine as compared with placebo (inactive treatment) on biomarkers related to cardiovascular risk and inflammation together with markers related to insulin therapy in type 1 diabetes. If colchicine is shown to be beneficial in type 1 diabetes, colchicine may hopefully also find its way into the treatment of cardiovascular risk and help increase the average life expectancy in type 1 diabetes.
Anticipated Outcome
It is the hope of the investigators that the results of the proposed trial may clarify if colchicine may reduce the risk of cardiovascular events such as heart attack or stroke in persons with type 1 diabetes.
Also, the investigators hope to be able to answer the question if colchicine may be safely added to insulin therapy in type 1 diabetes and to clarify any potential beneficial or adverse effects on insulin therapy and blood glucose control such as potential changes in insulin dosage, body weight, glycated hemoglobin (HbA1C) as measure of long-term blood glucose control, risk of low blood glucose levels and risk of diabetic ketoacidosis.
Finally, the investigators hope to bring new knowledge about how colchicine influences metabolism in type 1 diabetes, for example how colchicine influences body composition and lean and fat mass.
Relevance to T1D
Fifty million people world-wide have type 1 diabetes, and their average life expectancy is reduced by more than a decade due to cardiovascular disease as compared with people without diabetes. The anti-inflammatory drug colchicine (used for many years for the treatment of gout) is approved for the treatment of atherosclerotic cardiovascular disease by Health Canada and is also recommended in international treatment guidelines for lowering risk of cardiovascular events like heart attack or stroke in persons with pre-existent atherosclerotic cardiovascular disease. But it is unclear if colchicine exhibits the same cardiovascular benefits in type 1 diabetes, and the REC1TE trials investigates exactly if colchicine may be a beneficial treatment in type 1 diabetes and if colchicine may safely be added to insulin therapy. If colchicine shows cardiovascular benefits, the investigators hope that the REC1TE trial may help pave the way for including anti-inflammatory therapy with colchicine for the treatment of cardiovascular disease and help increase the average life expectancy in type 1 diabetes.