To determine whether supplementation with oral Vitamin K and or low dose colchicine vs placebo will reduce vascular calcification activity in patients with diabetes mellitus. The ViKCoVac Diabetes Study.

None listed

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality in the Western World and diabetes mellitus confers a doubling of CVD risk. Vascular calcification (VC) or hardening of the arteries is one of the most powerful independent predictors of cardiovascular events. VC is accelerated in patients with diabetes mellitus advancing vascular age by 5-10 years above chronological age. Progression of coronary calcification is associated with an adverse prognosis that is proportional to the rate of increase of coronary calcification over and above baseline calcification levels, indicating a pressing need for novel preventative therapies. The prevention of VC is a novel target that may effectively reduce risk of vascular events. Active vascular calcium deposition as opposed to stable patches of calcium may be detected with 18F-Fluoride PET/CT. This randomized double-blind placebo controlled 2x2 factorial trial will evaluate 2 novel therapies targeting a reduction of VC activity: Vitamin-K (VitK) 10mg per day targeting the increased activation of MGP, a potent local inhibitor of VC, and Colchicine 0.5mg per day, targeting inflammation via the accumulation of white blood cells in atherosclerotic plaque, a prerequisite for calcification. The effect of active treatment vs placebo for 3 months on the vascular calcification activity measured by PET-scan will be tested. Subsequently a natural history study will aim to define in a local patients with contemporary preventative treatment the rate of accumulation of VC (measured as the difference on Computed tomography (CT) between baseline and at 2y follow up). The study will be coordinated from the Department of Cardiology, Royal Perth Hospital. This study aims to determine whether one of these two novel therapies will reduce vascular calcification activity measured by positron-emission tomography/computed tomography (PET/CT) scan at baseline and after 3 months of: Oral Vitamin-K 10mg/day vs. placebo in patients with DM Oral colchicine 0.5mg/day vs. placebo in patients with DM Secondary aims are to determine the rate of accumulation of VC (measured as the difference on CT scan between baseline and at the 2yr follow-up). Patients with diabetes (type I, type II), aged 50 – 80yrs , will be approached at their regular clinic visit or during a hospital admission. Once randomised, they will be telephoned at 1 and 2 weeks to assess compliance, then asked to return to the cardiology clinic at 1, 2 and 3 months. Blood tests will be performed at 1 and 3 months.