Repurposing colchicine for reduction of residual inflammatory risk in type 1 diabetes (REC1TE): a randomized, double-blind, placebo-controlled, investigator-initiated trial

Prior treatment

• On permanent treatment with colchicine that is not discontinued within 30 days of visit 0
• Receipt of any investigational drug within 30 days prior to visit 0
• Systemic (oral or intravenous), long-term steroid therapy (topical or inhaled steroids are allowed)
• Hemodialysis or peritoneal dialysis therapy (since colchicine cannot be removed by dialysis or exchange transfusion)
• Renal or hepatic impairment treated with a P-gp inhibitor or a strong CYP3A4 inhibitor
• Other concomitant disease or treatment that according to the investigator's assessment makes the person unsuitable for study participation
• Alcohol/drug abuse

Other illness

• Known or suspected hypersensitivity to colchicine
• History of cirrhosis, chronic active hepatitis or severe hepatic disease
• Inflammatory bowel disease or chronic diarrhea
• Immunosuppressive therapy or state of chronic immunodeficiency, including infection with human immunodeficiency virus (HIV)
• Blood dyscrasias (e.g., myelodysplastic syndromes or related hematological disorders)

Lab values

• Hypoglycemia unawareness (inability to register low blood glucose) am modum Pedersen-Bjergaard, unless usage of CGM with alarm function
• Liver disease with elevated plasma alanine aminotransferase (ALT) > three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within seven days , and the last measured value as being conclusive)
• Pre-existing progressive neuromuscular disease or persons with creatinine kinase levels > three times the upper limit of normal (measured at visit 0 with the possibility of one repeat analysis within a week, and the last measured value as being conclusive)
• Thrombocyte count < 110 X 10^9/L
• Leukocyte cell count < 3.0 X 10^9/L

Age

• Cancer or lymphoproliferative disease unless in complete remission for > 5 years

Other

• Simultaneous participation in any other clinical intervention trial
• Intake of grape fruit juice during trial participation
• Fertile women not using chemical (tablet/pill, depot injection of progesterone, subdermal gestagen implantation, hormonal vaginal ring or transdermal hormonal patch) or mechanical (spirals) contraceptives
• Pregnant or nursing women

• Type 1 diabetes for more than five years according to World Health Organization criteria
• Age 18–80 years
• HbA1c < 80 mmol/mol
• Stable insulin therapy (defined as no change in insulin brand and not newly initiated continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI) therapy) and, if applicable, stable usage of glucose monitoring technology (e.g., continuous glucose monitoring CGM or intermittently scanned CGM) ≥ 3 months with either MDI or CSII
• C-reactive protein ≥ 2 mg/l (measured by high-sensitivity assay)
• Estimated glomerular filtration rate > 50 ml/min/l/1.73 m^2
• Either stable atherosclerotic cardiovascular (CV) disease (as defined by ischaemic heart disease including previous acute myocardial infarction, acute coronary syndrome and coronary revascularization; other arterial revascularization procedures; stroke and transient ischaemic attack; aortic aneurysm; peripheral arterial disease, including carotid atherosclerosis) or high risk thereof ((i.e., high or very high CV risk) as defined by the European Society of Cardiology (Eur Heart J 2020; 41: 255–323) or 10-year CV risk ≥ 20 % (i.e., high CV risk) as according to ‘Steno Type 1 Diabetes Risk Engine’ (https://steno.shinyapps.io/T1RiskEngine/)