Vitamin D and Arterial Function in Patients With Chronic Kidney Disease

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; Arterial Dysfunction
• Intervention / Treatment: Drug: Cholecalciferol; Drug: Calcitriol

• Study Type: Interventional
• Enrollment (Actual): 128
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Denver Clinical Translational Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Investigators: Principal Investigator: Jessica Kendrick, MD, University of Colorado, Denver

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2011
• Primary Completion (Actual): September 1, 2015
• Study Completion (Actual): September 1, 2015

Study Registration Dates

• First Submitted: June 27, 2011
• First Submitted That Met QC Criteria: June 27, 2011
• First Posted (Estimate): June 29, 2011

Study Record Updates

• Last Update Posted (Actual): September 28, 2018
• Last Update Submitted That Met QC Criteria: August 30, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Keywords: chronic kidney disease; vitamin D deficiency
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Micronutrients; Membrane Transport Modulators; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vasoconstrictor Agents; Calcium Channel Agonists; Vitamin D; Cholecalciferol; Calcitriol
• Other Study ID Numbers: 11-0521; 5K23DK087859 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No