Repurposing Colchicine for Reduction of Residual Inflammatory Risk in Type 1 Diabetes: A Randomized, Double-blind, Placebo-controlled, Investigator-initiated Trial

2022-502038-23-00

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.

2023-08-29

2026-06-15

2026-06-15

Recruiting

Early phase I

100

Inclusion Criteria: * Type 1 diabetes for more than five years according to World Health Organization criteria * Age 35-80 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/) Exclusion Criteria: * 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) * History of cirrhosis, chronic active hepatitis or severe hepatic disease * Inflammatory bowel disease or chronic diarrhea * 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) * Cancer or lymphoproliferative disease unless in complete remission for \> 5 years * Immunosuppressive therapy or state of chronic immunodeficiency, including infection with human immunodeficiency virus (HIV) * Blood dyscrasias (e.g., myelodysplastic syndromes or related hematological disorders) * Leukocyte cell count \< 3.0 X 10\^9/L * Thrombocyte count \< 110 X 10\^9/L * 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 * Intake of grapefruit juice during trial participation * Other concomitant disease or treatment that according to the investigator's assessment makes the person unsuitable for study participation * Alcohol/drug abuse * 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 * On permanent treatment with colchicine that is not discontinued within 30 days of screening visit * Known or suspected hypersensitivity to colchicine * Receipt of any investigational drug within 30 days prior to screening visit * Simultaneous participation in any other clinical intervention trial

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'RANDOMIZED', 'interventionModel': 'PARALLEL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}}, 'enrollmentInfo': {'count': 100, 'type': 'ESTIMATED'}}

2023-11-18