The aim of this clinical trial is to evaluate if colchicine in addition to standard of care improves markers of inflammation and cardiovascular disease in persons with type 1 diabetes. Participants will be assigned to either 0,5 mg colchicine daily or placebo in a 1:1 ratio for 26 weeks with the possibility of an additional 26 week extension of the intervention period. After the treatment period, there will a 5-year follow-up on all available outcome measures via electronic patient records for those who took part in the extension.
The current study aims to evaluate the efficacy of 0.5 mg colchicine once-daily added to existing standard of care in persons with established type 1 diabetes, existing arteriosclerotic cardiovascular disease (CVD) or at high risk thereof and C-reactive protein (CRP) ≥ 2 mg/L. Specifically, the primary objective is to determine the effect of colchicine (0.5 mg/daily) on levels of CRP (as assessed by high-sensitivity assays) as compared with placebo following 26-52 weeks of treatment. Additionally, the study will investigate the short and long-term effects of colchicine treatment on other markers of CVD and inflammation, markers of metabolism and markers of glycemic control in type 1 diabetes, including glycated hemoglobin (HbA1c), time spent in hypoglycemia (level 1 glucose readings 3.0-3.8 mmol/L and level 2 glucose readings \< 3.0 mmol/L), target glycemia (glucose readings 3.9-10 mmol/L) and hyperglycemia (level 1 glucose readings 10.1-13.9 mmol/L and level 2 glucose readings \> 13.9 mmol/L) together with measures of glycemic variability evaluated by continuous glucose monitoring (CGM), insulin dosage, risk of hypoglycemia, risk of diabetic ketoacidosis and body weight. During the 5-year follow-up, we will collect all available outcome measures via electronic patient records.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
102
Colchicine 0.5 mg once-daily
Placebo tablet once-daily
Center for Clinical Metabolic Research, Gentofte Hospital
Hellerup, Capital Region, Denmark
Change in fasting serum/plasma concentrations of C-reactive protein (CRP) measured by a high-sensitivity assay (hsCRP) (mg/L)
%-point
Time frame: From week 0 (baseline) to week 26 (end of treatment)
Change in fasting serum/plasma concentrations of C-reactive protein (CRP) measured by a high-sensitivity assay (hsCRP) (mg/L)
%-point
Time frame: From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension)
Change in fasting serum/plasma concentrations of hemoglobin A1c (mmol/mol)
%-point
Time frame: From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension)
Time spent in target blood glucose range (3.9 - 10 mmol/L) evaluated by a continous glucose monitor (CGM)
(% of 24 hours)
Time frame: From week 0 (baseline) to week 26 (end of treatment) or to 52 weeks (extension)
Time spent in hyperglycemia level 1 (10-13.9 mmol/L) evaluated by a continous glucose monitor (CGM)
(% of 24 hours)
Time frame: From week 0 (baseline) to week 26 (end of treatment) or to 52 weeks (extension)
Time spent in hyperglycemia level 2 (> 13.9 mmol/L) evaluated by a continous glucose monitor (CGM)
(% of 24 hours)
Time frame: From week 0 (baseline) to week 26 (end of treatment) or to 52 weeks (extension)
Time spent in hypoglycemia level 1 (3.0-3.8 mmol/L) evaluated by a continous glucose monitor (CGM)
(% of 24 hours)
Time frame: From week 0 (baseline) to week 26 (end of treatment) or to 52 weeks (extension)
Time spent in hypoglycemia level 2 (< 3.0 mmol/L)evaluated by a continous glucose monitor (CGM)
(% of 24 hours)
Time frame: From week 0 (baseline) to week 26 (end of treatment) or to 52 weeks (extension)
Insulin dosage
Number of units/day (both long- and short-acting insulin analogues)
Time frame: From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension)
Change in body weight (kg)
%-point
Time frame: From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension)
Change in waist:hip ratio
%-point
Time frame: From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension)
Change in fasting serum/plasma concentrations of low-density lipoprotein cholesterol (LDL) (mmol/L)
%-point
Time frame: From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension)
Change in fasting serum/plasma concentrations of interleukin (IL)-6 (pg/mL)
%-point
Time frame: From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension)
Change in fasting serum/plasma concentrations of tumor necrosis factor alpha (pg/mL)
%-point
Time frame: From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension)
Safety-related events
Serious adverse events (SAE), events of severe hypoglycemia, events of diabetic ketoacidosis
Time frame: From week 0 (baseline) to week 30 (safety follow-up) or to 56 weeks (extension)
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