E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Hormonal diseases [C19] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10045242 |
E.1.2 | Term | Type II diabetes mellitus |
E.1.2 | System Organ Class | 100000004861 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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. |
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E.2.2 | Secondary objectives of the trial |
- 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 reproducibility of dynamic FDG-PET/CT - 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.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of type 2 diabetes according to the World Health Organization definition - HbA1c level of 6,5 % (48 mmol/mol) or more - 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).
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E.4 | Principal 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.
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E.5 End points |
E.5.1 | Primary end point(s) |
Carotid-femoral pulse wave velocity assessed with applanation tonometry |
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E.5.1.1 | 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. |
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E.5.2 | 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 |
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E.5.2.1 | 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. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | No |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
This study aims to evaluate the vascular effects of colchicine in patients with type 2 diabetes and thereby provide insight to the mechanisms underlying the cardioprotective effects of the drug in patients at risk of cardiovascular disease. Moreover, this knowledge may help identify subjects that could benefit from treatment with colchicine treatment in the future. Finally, evaluation of dynamic FDG-PET/CT may help clear the way for a broader use of this newly developed method. |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 2 |
E.8.9.1 | In the Member State concerned months | 3 |
E.8.9.1 | In the Member State concerned days | 0 |