Effects of calcitriol on Arterial stiffness in T2DM patients with CKD
Research type
Research Study
Full title
Effect of active vitamin D treatment on arterial stiffness and albuminuria in patients with type 2 diabetes and stage 3 chronic kidney disease
IRAS ID
42785
Contact name
Luigi Gnudi
Eudract number
2010-018285-23
ISRCTN Number
xx
Research summary
Summary of Research
This study will investigate the effects of Calcitriol (vitamin D) on arterial stiffness and albuminuria in patients with type 2 diabetes and chronic kidney disease. Arterial stiffness and albuminuria are markers of cardiovascular and renal disease. Arterial stiffness as measured by aortic pulse wave velocity is a non-invasive measure of the elasticity of arteries and is a marker and predictor of cardiovascular risk. Ao-PWV measures the speed of transmission of the pulse wave along the aorta the largest blood vessel in the body. The greater the speed the greater the arterial stiffness. Interventions that reduce arterial stiffness may help prevent cardiovascular disease. Albuminuria is the presence of protein in the urine and is a sign of diabetic kidney damage and a marker of cardiovascular disease and risk. Reducing the amount of albuminuria can protect from progression of diabetic kidney disease. At present it is not known if treatment with Calcitriol can affect arterial stiffness and albuminuria in patients with diabetic kidney disease. This study will be a placebo controlled double blind clinical trial. All patients will continue with their current medical treatments for diabetes and kidney disease. Placebo contains no active ingredient and is used to determine whether the active medicine genuinely works under controlled conditions. One group of patients will be given Calcitriol and the other group will be given indistinguishable placebo tablets. Patients will be on treated for 48 weeks and the main outcome measures of this study are changes in arterial stiffness and albuminuria. If this study shows evidence that Calcitriol treatment improves arterial stiffness and albuminuria, this would enable a larger study to be performed to investigate if Calcitriol treatment can prevent cardiovascular and renal disease in patients with diabetes.
Summary of Results
Aims: Active vitamin D deficiency is associated with increased arterial stiffness as measured by aortic-pulse wave velocity (Ao-PWV) in people with type 2 diabetes (T2DM) and chronic kidney disease (CKD). There are no randomised controlled trials investigating the effect of active vitamin D treatment on Ao-PWV in people with T2DM and CKD.
Methods: A 48-week duration single-centre randomised double-blind parallel-group trial examined the impact of oral 1,25 dihydroxyvitamin D (calcitriol 0.25 mcg OD) as compared to placebo on a primary endpoint of Ao-PWV.
Results: In total, 127 (70% male) people were randomised (calcitriol n = 64 or placebo n = 63). There was no change in Ao-PWV observed, in the calcitriol group of 11.79 (±2.5) to 12.08 (3.0) m/s as compared to 10.90 (±2.4) to 11.39 (±2.6) m/s with placebo. The between-treatment group adjusted mean (95% confidence interval [(CI]] change was 0.23 (-0.58 to 1.05) m/s, P = .57. No effect of calcitriol was observed on central arterial pressures, albuminuria, serum calcium or phosphate levels. However, iPTH fell with calcitriol treatment (mean [95% CI] between-group difference of -27.8 (-42.3 to -13.2) pg/mL, P < .001.
Conclusion: In T2DM and stage 3 CKD, calcitriol as compared to placebo does not improve Ao-PWV or other markers of arterial stiffness. Our study does not provide evidence for the use of active vitamin D for improving arterial stiffness in T2DM with stage 3 CKD.
REC name
London - Westminster Research Ethics Committee
REC reference
10/H0802/26
Date of REC Opinion
29 Apr 2010
REC opinion
Further Information Favourable Opinion