Repurposing Colchicine for Reduction of Residual Inflammatory Risk in Type 1 Diabetes

Prior treatment

• 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
• On permanent treatment with colchicine that is not discontinued within 30 days of screening visit
• Receipt of any investigational drug within 30 days prior to screening visit

Other illness

• 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)
• Known or suspected hypersensitivity to colchicine

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 screening 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 screening with the possibility of one repeat analysis within a week, and the last measured value as being conclusive)
• Leukocyte cell count \< 3.0 X 10\^9/L
• Thrombocyte count \< 110 X 10\^9/L

Age

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

Other

• Intake of grapefruit juice during trial participation
• Fertile women not using hormonal (tablet/pill, depot injection of progesterone, subdermal gestagen implantation, hormone intrauterine devices (IUD), hormonal vaginal ring or transdermal hormonal patch), chemical (copper IUD) or mechanical (condom, femidom, sterilization) contraceptives
• Pregnant or nursing women
• Simultaneous participation in any other clinical intervention trial

• Type 1 diabetes for more than five years according to World Health Organization criteria
• Age 18-80 years
• Hemoglobin A1c \< 80 mmol/mol
• Stable insulin therapy (defined as no change in insulin brand and no newly initiated continous subcutaneus insulin infusion (CSII) or multiple-daily injection (MDI) therapy) and, if applicable, stable usage of glucose monitoring technology (e.g., continous glucose monitor (CGM) or intermittently scanned CGM) ≥ 3 months with either MDI or CSII
• CRP ≥ 2 mg/L (measured by high-sensitivity assay)
• eGFR \> 50 mL/min/L/1.73 m\^2
• Either stable arteriosclerotic cardiovascular disease (ASCVD) (as defined by ischemic heart disease including previous acute myocardial infarction, acute coronary syndrome and coronary revascularization; other arterial revascularization procedures; stroke and transient ischemic attack; aortic aneurysm; peripheral arterial disease, including carotid atherosclerosis)
• and/or risk of cardiovascular (CV) death \> 5 % within 10 years (i.e., high or very high CV risk) as defined by the European Society of Cardiology 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/)