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

Levin A, Perry T, De Zoysa P, Sigrist MK, Humphries K, Tang M, Djurdjev O - BMC Cardiovasc Disord (2014)

Bottom Line: Vitamin D deficiency is associated with cardiovascular (CV) risk in multiple populations, including those with chronic kidney disease (CKD).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.

View Article: PubMed Central - PubMed

Affiliation: University of British Columbia, 1081 Burrard Street, Room 6010A, Vancouver, BC V6Z 1Y6, Canada. alevin@providencehealth.bc.ca.

ABSTRACT

Background: 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.

Methods/design: 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.

Discussion: 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.

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

Show MeSH

Related in: MedlinePlus

The study plan depicts the timeline for the completion of the study. Screening/recruitment includes the 3 month washout period. Vitamin D doses will be administered for 6 months allowing for the inclusion criteria. PWV will be measured at baseline (-3 months), post washout period (0 months) and post treatment (6 months) for both treatment arms and their respective placebos.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
getmorefigures.php?uid=PMC4230794&req=5

Fig1: The study plan depicts the timeline for the completion of the study. Screening/recruitment includes the 3 month washout period. Vitamin D doses will be administered for 6 months allowing for the inclusion criteria. PWV will be measured at baseline (-3 months), post washout period (0 months) and post treatment (6 months) for both treatment arms and their respective placebos.

Mentions: This will be a 3 arm prospective randomized double blind placebo controlled study of 128 stable CKD subjects examining the impact of vitamin D supplementation (1,25 vitamin D or 25 vitamin D formulations) compared to placebo on arterial stiffness and other parameters of vascular health. The study plan shown in Figure 1 will combine physiological experiments in a well characterized cohort of patients with CKD, and utilize observational study methods to test and explore additional related hypotheses.Figure 1


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

Levin A, Perry T, De Zoysa P, Sigrist MK, Humphries K, Tang M, Djurdjev O - BMC Cardiovasc Disord (2014)

The study plan depicts the timeline for the completion of the study. Screening/recruitment includes the 3 month washout period. Vitamin D doses will be administered for 6 months allowing for the inclusion criteria. PWV will be measured at baseline (-3 months), post washout period (0 months) and post treatment (6 months) for both treatment arms and their respective placebos.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC4230794&req=5

Fig1: The study plan depicts the timeline for the completion of the study. Screening/recruitment includes the 3 month washout period. Vitamin D doses will be administered for 6 months allowing for the inclusion criteria. PWV will be measured at baseline (-3 months), post washout period (0 months) and post treatment (6 months) for both treatment arms and their respective placebos.
Mentions: This will be a 3 arm prospective randomized double blind placebo controlled study of 128 stable CKD subjects examining the impact of vitamin D supplementation (1,25 vitamin D or 25 vitamin D formulations) compared to placebo on arterial stiffness and other parameters of vascular health. The study plan shown in Figure 1 will combine physiological experiments in a well characterized cohort of patients with CKD, and utilize observational study methods to test and explore additional related hypotheses.Figure 1

Bottom Line: Vitamin D deficiency is associated with cardiovascular (CV) risk in multiple populations, including those with chronic kidney disease (CKD).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.

View Article: PubMed Central - PubMed

Affiliation: University of British Columbia, 1081 Burrard Street, Room 6010A, Vancouver, BC V6Z 1Y6, Canada. alevin@providencehealth.bc.ca.

ABSTRACT

Background: 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.

Methods/design: 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.

Discussion: 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.

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

Show MeSH
Related in: MedlinePlus