Repurposing Colchicine for Reduction of Residual Inflammatory Risk in Type 1 Diabetes
- Conditions
- Type 1 DiabetesCardiovascular DiseasesChronic Inflammation
- Interventions
- Drug: Placebo
- Registration Number
- NCT05949281
- Lead Sponsor
- Asger Lund, MD
- Brief Summary
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.
- Detailed Description
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 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.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 100
- 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/)
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Colchicine Colchicine 0.5 MG Oral Tablet Colchicine tablet 0.5 mg once-daily Placebo Placebo Placebo tablet once-daily
- Primary Outcome Measures
Name Time Method Change in fasting serum/plasma concentrations of C-reactive protein (CRP) measured by a high-sensitivity assay (hsCRP) (mg/L) From week 0 (baseline) to week 26 (end of treatment) %-point
- Secondary Outcome Measures
Name Time Method Change in fasting serum/plasma concentrations of hemoglobin A1c (mmol/mol) From week 0 (baseline) to week 30 (safety follow-up) %-point
Time spent in target blood glucose range (3.9 - 10 mmol/L) evaluated by a continous glucose monitor (CGM) From week 0 (baseline) to week 26 (end of treatment) (% of 24 hours)
Change in fasting serum/plasma concentrations of C-reactive protein (CRP) measured by a high-sensitivity assay (hsCRP) (mg/L) From week 0 (baseline) to week 30 (safety follow-up) %-point
Time spent in hyperglycemia level 1 (10-13.9 mmol/L) evaluated by a continous glucose monitor (CGM) From week 0 (baseline) to week 26 (end of treatment) (% of 24 hours)
Time spent in hyperglycemia level 2 (> 13.9 mmol/L) evaluated by a continous glucose monitor (CGM) From week 0 (baseline) to week 26 (end of treatment) (% of 24 hours)
Time spent in hypoglycemia level 1 (3.0-3.8 mmol/L) evaluated by a continous glucose monitor (CGM) From week 0 (baseline) to week 26 (end of treatment) (% of 24 hours)
Time spent in hypoglycemia level 2 (< 3.0 mmol/L)evaluated by a continous glucose monitor (CGM) From week 0 (baseline) to week 26 (end of treatment) (% of 24 hours)
Insulin dosage From week 0 (baseline) to week 30 (safety follow-up) Number of units/day (both long- and short-acting insulin analogues)
Change in body weight (kg) From week 0 (baseline) to week 30 (safety follow-up) %-point
Change in waist:hip ratio From week 0 (baseline) to week 30 (safety follow-up) %-point
Change in fasting serum/plasma concentrations of low-density lipoprotein cholesterol (LDL) (mmol/L) From week 0 (baseline) to week 30 (safety follow-up) %-point
Change in fasting serum/plasma concentrations of interleukin (IL)-6 (pg/mL) From week 0 (baseline) to week 30 (safety follow-up) %-point
Change in fasting serum/plasma concentrations of tumor necrosis factor alpha (pg/mL) From week 0 (baseline) to week 30 (safety follow-up) %-point
Safety-related events From week 0 (baseline) to week 30 (safety follow-up) Serious adverse events (SAE), events of severe hypoglycemia, events of diabetic ketoacidosis
Trial Locations
- Locations (1)
Center for Clinical Metabolic Research, Gentofte Hospital
🇩🇰Hellerup, Capital Region, Denmark