The Role of Colchicine in Preventing Atherosclerotic Cardiovascular Disease in Type 2 Diabetes (Col-DM Study)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Change from Baseline in Mean-Maximum Carotid Intima-Media Thickness (Mean-Maximum CIMT)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 21 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Colchicine
Colchicine 0.5 mg orally once daily for 24 weeks, in addition to usual risk-factor-based therapy
干预措施: Colchicine 0.5 MG Oral Tablet Once Daily (Drug)
Placebo
Matched placebo orally once daily for 24 weeks, in addition to usual risk-factor-based therapy
干预措施: Placebo (Drug)
结局指标
主要结局
Change from Baseline in Mean-Maximum Carotid Intima-Media Thickness (Mean-Maximum CIMT)
时间窗: Baseline and 24 weeks
Mean-maximum CIMT is defined as the average of the maximum CIMT values obtained from the far wall of the left and right common carotid arteries, each derived from six measurements taken across three projections (lateral, anterior, and posterior) at 1 cm proximal to the carotid bifurcation, measured by high-resolution B-mode carotid ultrasonography.
次要结局
- Change from Baseline in Mean Carotid Intima-Media Thickness (avgCIMT)(Baseline and 24 weeks)
- Change from Baseline in Carotid Plaque Volume(Baseline and 24 weeks)
- Change from Baseline in Endothelial Function (Flow-Mediated Dilation)(Baseline and 24 weeks)
- Change from Baseline in Microvascular Reactivity (Reactive Hyperaemia Index)(Baseline and 24 weeks)
- Change from Baseline in Arterial Stiffness (Pulse Wave Velocity)(Baseline and 24 weeks)
- Change from Baseline in Arterial Stiffness (Cardio-Ankle Vascular Index)(Baseline and 24 weeks)
- Change from Baseline in Skin Advanced Glycation End Products (Skin Autofluorescence)(Baseline and 24 weeks)
- Change from Baseline in Retinal Layer Thickness (Optical Coherence Tomography)(Baseline and 24 weeks)
- Change from Baseline in Retinal Microvascular Density (Optical Coherence Tomography Angiography)(Baseline and 24 weeks)
- Change from Baseline in High-Sensitivity C-Reactive Protein (hsCRP)(Baseline and 24 weeks)
- Change from Baseline in Interleukin-6 (IL-6)(Baseline and 24 weeks)
- Change from Baseline in Plasminogen Activator Inhibitor-1 (PAI-1)(Baseline and 24 weeks)
- Change from Baseline in Cell-Free DNA (NETosis Marker)(Baseline and 24 weeks)
- Change from Baseline in Citrullinated Histone H3 (NETosis Marker)(Baseline and 24 weeks)
- Change from Baseline in E-selectin(Baseline and 24 weeks)
- Change from Baseline in Intercellular Adhesion Molecule-1 (ICAM-1)(Baseline and 24 weeks)
- Change from Baseline in Vascular Cell Adhesion Molecule-1 (VCAM-1)(Baseline and 24 weeks)
- Change from Baseline in Oxidative Stress Index(Baseline and 24 weeks)
- Change from Baseline in Thrombotic Potential (Clot Waveform Analysis)(Baseline and 24 weeks)
- Change from Baseline in Von Willebrand Factor Antigen (VWF:Ag)(Baseline and 24 weeks)
- Change from Baseline in Von Willebrand Factor Activity (VWF:Act)(Baseline and 24 weeks)
- Change from Baseline in Factor VIII(Baseline and 24 weeks)
- Change from Baseline in Thrombin Generation(Baseline and 24 weeks)
- Change from Baseline in Oxidised LDL (Ox-LDL)(Baseline and 24 weeks)
- Change from Baseline in Atherogenic Lipid Subfractions(Baseline and 24 weeks)