A randomized control trial to assess the impact of vitamin D supplementation compared to placebo on vascular stiffness in chronic kidney disease patients

Vitamin D deficiency is associated with cardiovascular (CV) risk in multiple populations, including those with chronic kidney disease (CKD). The active form of the hormone (1,25 OH₂D₃₎ binds to receptors in multiple organs. CKD patients are deficient in both 25 Vitamin D and 1,25 OH₂D₃. Clinical trial data demonstrating the benefits of vitamin D formulations are limited, and fail to show significant benefits on CV outcomes, and have compared different compounds, in various populations, and focused on a variety of outcomes. A understanding of the mechanism by which different vitamin D compounds confer CV protection in CKD is important for the design of future studies.

This 3 arm randomized prospective double-blinded placebo-controlled study examining the impact of calcitriol (1,25 OH₂D₃) and 25-hydroxyvitamin D3 supplementation compared to placebo on vascular stiffness, as measured by pulse wave velocity (PWV). Patients are enrolled from 2 tertiary care institutions if they meet inclusion criteria (stable estimated glomerular filtration rate (eGFR) between 15-45ml/min, <±5ml/min change in previous 6 months), on stable doses of renin-angiotensin aldosterone system blockade. For those already receiving vitamin D therapies, a 3 month washout period before randomization is mandatory. Treatment duration is 6 months; medications are given thrice weekly in fixed doses. The primary outcome measure is Vascular stiffness, measured non-invasively by pulse wave velocity (PWV). Other measurements include BP, kidney function and serial blood levels of biomarkers. The primary analysis will compare any vitamin D therapy versus placebo for the primary outcome defined as the change of PWV from baseline to 6 months. Analysis of covariance will be used to detect differences between vitamin D preparations in the magnitude of reduction in PWV.

This study is novel in that we are using a robust study design in CKD patients (not on dialysis) comparing placebo to different forms of vitamin D supplementation in fixed doses, irrespective of baseline values. We hope to demonstrate the biological mechanistic effect of vitamin D supplementation on vascular function in order for this information to be used in designing larger randomized controlled trials.

Current Controlled Trials NCT01247311. Date of Registration: November 12, 2010.