Overview
This study will test whether a low-cost anti-inflammatory medicine called colchicine can help protect the blood vessels of people with type 2 diabetes. Diabetes speeds up hardening of the arteries (atherosclerosis), partly because of ongoing low-grade inflammation. Colchicine has already been shown to help prevent heart attacks and strokes in people who already have heart disease; this study looks at whether it can also help prevent early blood vessel damage before heart disease develops. Around 300 adults with type 2 diabetes will be randomly assigned to take colchicine or a placebo (dummy pill) once daily for 24 weeks, in addition to their usual diabetes and heart-risk medications. Neither participants nor the study team will know who is taking colchicine or placebo. The main measurement will be the change in the thickness of the wall of the neck (carotid) artery, measured by ultrasound, which is an early sign of blood vessel disease. The study will also look at markers of inflammation in the blood, blood vessel stiffness and function, and changes in the gut bacteria.
Description
Cardiovascular disease remains the leading cause of death in T2DM, occurring earlier and at substantially higher rates than in the general population. Despite optimisation of conventional risk factors, residual cardiovascular risk remains high, with chronic low-grade inflammation driven by dysregulated neutrophil activity recognised as a key contributor. Patients with T2DM exhibit a distinct pro-inflammatory neutrophil phenotype characterised by increased neutrophil extracellular trap (NET) formation, heightened endothelial adherence, and altered rolling kinetics, which correlates with impaired vascular function and subclinical atherosclerosis.
Colchicine inhibits neutrophil activation, migration, and NET formation, and has demonstrated efficacy in secondary cardiovascular prevention in large randomised trials. Evidence in primary prevention, particularly in T2DM, remains limited. Col-DM takes a precision medicine approach, hypothesising that colchicine's benefit will be concentrated among T2DM patients with a high-risk inflamed neutrophil signature rather than being uniform across the broader population.
Col-DM is a 24-week, parallel-group, Phase 2 randomised controlled trial. Adults with T2DM and no prior atherosclerotic cardiovascular disease are randomised 1:1 to colchicine 0.5 mg daily or matched placebo, stratified by neutrophil inflammatory phenotype classified using a microfluidic organ-on-chip platform. The primary outcome is progression of carotid intima-media thickness (CIMT), estimated overall and separately within each neutrophil-signature stratum. Secondary outcomes cover vascular function, inflammatory and oxidative stress biomarkers, and thrombotic potential. Gut microbiome composition is examined as an exploratory outcome. All outcome measures are estimated overall and separately within each neutrophil-signature stratum. Safety is monitored by an independent Data and Safety Monitoring Committee.
Eligibility
Inclusion Criteria:
- T2DM on stable diabetes medications (no change in last 3 months)
- At least one other comorbidity of hypertension, dyslipidaemia and/or obesity (BMI ≥27), with no previous history of ASCVD
- Able to provide informed consent
Exclusion Criteria:
- Recent hospitalization or acute infections within last 2 weeks.
- Current Treatment with corticosteroids or immunosuppressive agents
- Pre-existing malignancies or other terminal conditions with limited prognosis
- Pregnancy
- Breastfeeding
- Inability to provide written consent
- Renal impairment (eGFR\< 60ml/min)
- Liver cirrhosis or ALT/AST \>3x ULN
- Pharmacogenomics indicative of adverse effects
- Hypersensitivity to the active substance or to the following excipients: Lactose, Maize starch, Sodium laurilsulfate, Magnesium stearate
- Known blood dyscrasia
- Women of childbearing age who are keen to conceive in the next 1 year
- Taking a strong P-glycoprotein inhibitor (e.g. cyclosporine, ranolazine) or a strong CYP3A4 inhibitor
- Known myositis with raised creatine kinase with statins (statin myopathy).
- Gout attack within the last 1 year
- Currently taking Aspirin
- Taking any oral contraceptives
