Vitamin D and Arterial Function in Patients With Chronic Kidney Disease

Study Overview
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Brief Summary
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The purpose of this study is to determine whether nutritional (cholecalciferol) or active vitamin D (calcitriol) supplementation improves vascular endothelial function in patients with stage IIIB and IV chronic kidney disease with vitamin D insufficiency or deficiency. The investigators hypothesize that the use of calcitriol supplementation will result in improved vascular endothelial function as compared to cholecalciferol supplementation.

Official Title
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Vitamin D and Arterial Function in Patients With Chronic Kidney Disease

Conditions
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Arterial Dysfunction, Chronic Kidney Disease

Intervention / Treatment
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* Drug: Cholecalciferol
* Drug: Calcitriol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Chronic kidney disease stage IIIB or IV by 4 parameter Modified Diet in Renal Diseases Formula (Estimated Glomerular Filtration Rate [GFR] 44-15 ml/min/1.73m2) Vitamin D (D2 + D3) deficient, defined as serum 25(OH)D level < 30 ng/mL Corrected serum calcium < 10.2 mg/dL Serum phosphate < 4.6 mg/dL Serum albumin > 3.0 g/dL Body mass index < 40 kg/m2 Ability to give informed consent Exclusion Criteria: Significant co-morbid conditions that lead the investigator to conclude that life expectancy is less than 1 year Expected to undergo living related kidney transplant in next 6 months Pregnant, breastfeeding, or unwilling to use adequate birth control History of severe liver disease Nephrotic range proteinuria (> 3.5 gm/day) Use of active vitamin D analogs within 30 days of randomization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cholecalciferol<br>Cholecalciferol 4000 IU capsule by mouth daily x 1 month then 2000 IU capsule by mouth daily x 5 months | Drug: Cholecalciferol<br> <br> |
| Experimental: Calcitriol<br>Calcitriol 0.25 mcg capsule by mouth daily x 1 month then 0.5 mcg capsule by mouth daily x 5 months | Drug: Calcitriol<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the Difference Between the Calcitriol and Cholecalciferol Groups in Conduit Artery Endothelium-dependent Dilation (EDD) in Response to Treatment. | EDD will be measured by brachial artery flow-mediated dilation (FMD). The mean change in percent FMD from baseline will be documented. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Compare the Efficacy of Calcitriol and Cholecalciferol Supplementation on Plasma Concentrations of C-reactive Protein | Secondary aims are focused to explore whether vitamin D improves vascular endothelial function through decreases in inflammation | 6 months | 
| Compare the Effect of Calcitriol and Cholecalciferol Supplementation on Vascular Endothelial Cell Expression of Nf-kB | The effect of calcitriol and cholecalciferol supplementation will be evaluated calculating the mean change in total vascular endothelial cell NFkB expression. NFkB expression is given as arbitrary units and represent ratios of endothelial cell protein expression to human umbilical vein endothelial cell (HUVEC) expression in order to account for any variation in the staining procedure. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic kidney disease, vitamin D deficiency