Vitamin D and Arterial Function in Patients With Chronic Kidney Disease

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT01384539
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 128
• Location: 1
• Arms: 2
• Actual Duration (Months): 50
• Patients Per Site Per Month: 2.6

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Arterial Dysfunction; Chronic Kidney Disease	Drug: Cholecalciferol; Drug: Calcitriol	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 128 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Vitamin D and Arterial Function in Patients With Chronic Kidney Disease
• Actual Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Sep 1, 2015
• Actual Study Completion Date: Sep 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Compare the Difference Between the Calcitriol and Cholecalciferol Groups in Conduit Artery Endothelium-dependent Dilation (EDD) in Response to Treatment. [6 months]

   EDD will be measured by brachial artery flow-mediated dilation (FMD). The mean change in percent FMD from baseline will be documented.

Secondary Outcome Measures

1. Compare the Efficacy of Calcitriol and Cholecalciferol Supplementation on Plasma Concentrations of C-reactive Protein [6 months]

   Secondary aims are focused to explore whether vitamin D improves vascular endothelial function through decreases in inflammation

2. Compare the Effect of Calcitriol and Cholecalciferol Supplementation on Vascular Endothelial Cell Expression of Nf-kB [6 months]

   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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Denver Clinical Translational Research Center	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Jessica Kendrick, MD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT01384539
• Other Study ID Numbers: 11-0521; 5K23DK087859
• First Posted: Jun 29, 2011
• Last Update Posted: Sep 28, 2018
• Last Verified: Aug 1, 2018

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by University of Colorado, Denver: chronic kidney disease; vitamin D deficiency
• Additional relevant MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Cholecalciferol; Vitamin D; Calcitriol

Study Results

Participant Flow

Arm/Group Title	Cholecalciferol	Calcitriol
Arm/Group Description	Cholecalciferol 4000 IU capsule by mouth daily x 1 month then 2000 IU capsule by mouth daily x 5 months Cholecalciferol	Calcitriol 0.25 mcg capsule by mouth daily x 1 month then 0.5 mcg capsule by mouth daily x 5 months Calcitriol
Period Title: Overall Study
STARTED	64	64
COMPLETED	58	57
NOT COMPLETED	6	7

Baseline Characteristics

Arm/Group Title	Cholecalciferol	Calcitriol	Total
Arm/Group Description	Cholecalciferol 4000 IU capsule by mouth daily x 1 month then 2000 IU capsule by mouth daily x 5 months Cholecalciferol	Calcitriol 0.25 mcg capsule by mouth daily x 1 month then 0.5 mcg capsule by mouth daily x 5 months Calcitriol	Total of all reporting groups
Overall Participants	64	64	128
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (13)	59 (12)	58 (12)
Sex: Female, Male (Count of Participants)
Female	19 29.7%	23 35.9%	42 32.8%
Male	45 70.3%	41 64.1%	86 67.2%
Race/Ethnicity, Customized (Count of Participants)
Non-Hispanic White	23 35.9%	23 35.9%	46 35.9%
Non-Hispanic Black	18 28.1%	14 21.9%	32 25%
Hispanic	16 25%	23 35.9%	39 30.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cholecalciferol	Calcitriol
Arm/Group Description	Cholecalciferol 4000 IU capsule by mouth daily x 1 month then 2000 IU capsule by mouth daily x 5 months Cholecalciferol	Calcitriol 0.25 mcg capsule by mouth daily x 1 month then 0.5 mcg capsule by mouth daily x 5 months Calcitriol
Measure Participants	58	57
Mean (Standard Deviation) [percent change in FMD]	-0.5 (4.2)	0.3 (3.5)

2. Secondary Outcome

Title	Compare the Efficacy of Calcitriol and Cholecalciferol Supplementation on Plasma Concentrations of C-reactive Protein
Description	Secondary aims are focused to explore whether vitamin D improves vascular endothelial function through decreases in inflammation
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cholecalciferol	Calcitriol
Arm/Group Description	Cholecalciferol 4000 IU capsule by mouth daily x 1 month then 2000 IU capsule by mouth daily x 5 months Cholecalciferol	Calcitriol 0.25 mcg capsule by mouth daily x 1 month then 0.5 mcg capsule by mouth daily x 5 months Calcitriol
Measure Participants	58	57
Baseline	3.0	3.4
End of Study	3.1	3.9

3. Secondary Outcome

Title	Compare the Effect of Calcitriol and Cholecalciferol Supplementation on Vascular Endothelial Cell Expression of Nf-kB
Description	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.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cholecalciferol	Calcitriol
Arm/Group Description	Cholecalciferol 4000 IU capsule by mouth daily x 1 month then 2000 IU capsule by mouth daily x 5 months Cholecalciferol	Calcitriol 0.25 mcg capsule by mouth daily x 1 month then 0.5 mcg capsule by mouth daily x 5 months Calcitriol
Measure Participants	58	57
Mean (Standard Deviation) [ratio of NFkB to HUVEC expression]	0.03 (0.1)	-0.01 (0.1)

Adverse Events

Arm/Group Title	Cholecalciferol		Calcitriol
Arm/Group Description	Cholecalciferol 4000 IU capsule by mouth daily x 1 month then 2000 IU capsule by mouth daily x 5 months Cholecalciferol		Calcitriol 0.25 mcg capsule by mouth daily x 1 month then 0.5 mcg capsule by mouth daily x 5 months Calcitriol
All Cause Mortality
	Cholecalciferol		Calcitriol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/64 (3.1%)		0/64 (0%)
Serious Adverse Events
	Cholecalciferol		Calcitriol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/64 (14.1%)		5/64 (7.8%)
Cardiac disorders
Hospitalization	9/64 (14.1%)	9	5/64 (7.8%)	5
Other (Not Including Serious) Adverse Events
	Cholecalciferol		Calcitriol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/64 (1.6%)		4/64 (6.3%)
Renal and urinary disorders
Hypercalcemia	1/64 (1.6%)	1	4/64 (6.3%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.