Type 2 diabetes mellitus MedDRA version: 21.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861
Conditions
Interventions
Trade Name: Colchicin "Tiofarma"
Pharmaceutical Form: Tablet
Pharmaceutical form of the placebo: Tablet
Route of administration of the placebo: Oral use
Sponsors
Aarhus University Hospital, Steno Diabetes Center Aarhus
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Diagnosis of type 2 diabetes according to the World Health Organization definition - HbA1c level of 6,5 % (48 mmol/mol) or more - High sensitivity C-reactive protein > 2 mg/l - Age of 50 years or more with established cardiovascular disease (prior myocardial infarction, prior stroke or prior transient ischemic attack, prior coronary, carotid or peripheral arterial revascularization, more than 50 % stenosis on angiography or imaging of coronary, carotid or lower extremities arteries, history of symptomatic coronary heart disease documented by e.g. positive exercise stress test or any cardiac imaging or unstable angina with electrocardiography changes or Age of 60 years or more with at least one cardiovascular risk factor (persistent microalbuminuria (30-299 mg/g) or proteinuria, hypertension and left ventricular hypertrophy by electrogram or imaging, persistent hypertension despite antihypertensive treatment, left ventricular systolic or diastolic dysfunction by imaging, smoking or ankle/brachial index less than 0.9). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 50
Exclusion criteria
Exclusion criteria: - Previous allergic/hypersensitivity reaction to colchicine - Colchicine treatment for another cause - Poorly controlled medical condition, e.g. congestive heart failure (New York Heart Association III-IV), recent stroke or any other condition that in the opinion of the investigator will put the trial participant at risk if participating in the trial - Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m2 - Anemia, thrombocytopenia or leucopenia defined as any of the following, measured within the last 3 months: • Hemoglobin < 7 mmol/L • Platelet count < 110 x 109/L • White blood cell count < 3.0 x 109/L - Inability to give informed consent - Active cancer diagnosis other than basal cell carcinoma - Indication of liver disease (serum ALAT above 3 x upper limit of normal) - Bariatric surgery within the past two years and other gastrointestinal surgeries that induce chronic malabsorption - Treatment with systemic steroids at time of randomization - Treatment with potent inhibitors of cytochrome P450 3A4 or P-glycoprotein (Appendix 1) - Treatment with any biologic drug targeting the immune system (e.g., TNF-alfa inhibitors) - Vaccination (e.g., against COVID-19) within 14 days prior to inclusion - Alcohol or drug abuse within 3 months of informed consent that would interfere with trial participation or any ongoing condition leading to decreased compliance with study procedures or study drug intake - Pregnancy or breastfeeding - Chronic inflammatory bowel disease (Crohn’s disease or ulcerative colitis) or chronic diarrhea In each group, 15 patients will have FDG-PET/CT performed. These patients cannot have any contraindications to FDG-PET/CT i.e., allergy toward contrast agent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to evaluate the effect of colchicine on arterial stiffness assessed as carotid-femoral pulse wave velocity compared to placebo in patients with type 2 diabetes.;Secondary Objective: - To evaluate the effect of colchicine on endothelial function assessed by peripheral arterial tonometry compared to placebo in patients with type 2 diabetes. - To evaluate the effect of colchicine on vascular inflammation assessed by FDG-PET/CT of the aorta compared to placebo in patients with type 2 diabetes. - To evaluate the effect of colchicine on cardiac autonomic function assessed as heart rate variability and cardiac vagal tone compared to placebo in patients with type 2 diabetes. - To investigate whether dynamic FDG-PET/CT is superior to static FDG-PET/CT to detect changes in inflammation of the aortic wall. - To evaluate the effect of colchicine on biochemical markers of inflammation, 24-hour ambulatory blood pressure, 24-hour arterial stiffness, changes in urinary albumin excretion, changes in platelet aggregation and changes in other markers of hemostasis and fibrinolysis. ;Primary end point(s): Carotid-femoral pulse wave velocity assessed with applanation tonometry;Timepoint(s) of evaluation of this end point: At baseline and after 26 weeks of treatment with either colchicine 0.5 mg once daily or placebo. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Endothelial function assessed as Reactive Hyperemia Index using peripheral arterial tonometry - Vascular inflammation of the aortic wall assessed with FDG-PET/CT - Cardiac autonomic function assessed as heart rate variability and cardiac vagal tone - 24-hour arterial stiffness and 24-hour ambulatory blood pressure - Biochemical end points: Changes in biomarkers of inflammation, urinary albumin excretion, platelet aggregation, and measures of secondary hemostasis and fibrinolysis;Timepoint(s) of evaluation of this end point: Secondary end points will be assessed At baseline and after 26 weeks of treatment with either colchicine 0.5 mg once daily or placebo. | — |
Countries
Denmark
Contacts
Public ContactMedical/Steno Aarhus Research Lab
Aarhus University Hospital, Steno Diabetes Center Aarhus
Outcome results
None listed