How Vitamin D Analogues Affect Endothelial Cells in Patients on Dialysis

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00528788
• Collaborator: Genzyme, a Sanofi Company (Industry)
• Enrollment: 24
• Location: 1
• Arm: 1
• Duration (Months): 59
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

Patients with chronic kidney disease and end stage renal disease have greater cardiovascular risk than the general population. Vitamin D analogues have been shown in observational studies to have mortality benefit for these patients. This study is designed to investigate doxercalciferol's effect on the vasculature (i.e. endothelial cell function) as a possible mechanism to explain the mortality benefit.

Condition or Disease	Intervention/Treatment	Phase
Hyperparathyroidism, Secondary; Kidney Failure, Chronic	Drug: doxercalciferol	Phase 4

Study Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Doxercalciferol on Endothelial Cell Function in End Stage Renal Disease
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Aug 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Pre and post doxicalciferol ESRD: all patients with secondary hyperparathyroidism who are vitamin D naive will receive doxercalciferol 2 mcg or 4 mcg 3 times per week fopr 30 days (1 month). Blood work and vascular laboratory studies will be performed pre and post treatment.	Drug: doxercalciferol

Outcome Measures

Primary Outcome Measures

1. Change in Endothelial Cell Function [1 month]

   Endothelial cell function was assessed by performing flow mediated vasodilatation testing in a vascular laboratory prior to receiving doxercalciferol (either 2 mcg or 4 mcg 3 times per week at hemodialysis) and then after receiving the drug for 30 days.

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Stage 5 Chronic Kidney Disease

• Hyperparathyroidism (PTH>300) requiring vitamin D therapy

• Age 18-80 years old

• Ability to provide informed consent

Exclusion Criteria:

• Subjects with neovascularization present, such as neoplasm, active wounds or significant retinopathy

• Subjects with contraindications or allergy to vitamin D

• Subjects currently on vitamin D therapy or a history of vitamin D therapy in the previous 60 days

• Serum phosphorus > 6

• Serum calcium > 10.5

• contraindications to nitroglycerin (such as being on sildenafil)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center Dialysis Unit	Durham	North Carolina	United States	27705

Sponsors and Collaborators

• Duke University
• Genzyme, a Sanofi Company

Investigators

• Principal Investigator: Jula Inrig, MD, MHS, University Texas-Southwestern
• Principal Investigator: Lynda Szczech, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00528788
• Other Study ID Numbers: Pro00001559
• First Posted: Sep 12, 2007
• Last Update Posted: Jan 22, 2016
• Last Verified: Aug 1, 2012

• Additional relevant MeSH terms: Renal Insufficiency; Kidney Failure, Chronic; Hyperparathyroidism; Hyperparathyroidism, Secondary; 1 alpha-hydroxyergocalciferol

Study Results

Participant Flow

Recruitment Details	We prospectively enrolled 24 hemodialysis patients with secondary hyperparathyroidism into an open-label 30-day observational study.
Pre-assignment Detail	Participants underwent review of history and meds. Hemodialysis (HD) blood was drawn. seen in vascular laboratory for testing of endothelial cell function and arterial stiffness. Doxercalciferol was initiated at dose of 2 mcg IV 3x/wk or 4 mcg IV 3x/wk. After 30 days of medication, repeat blood drawn and repeat testing in vascular laboratory.

Arm/Group Title	Pre Doxercalciferol/Post Doxercalciferol
Arm/Group Description	all end stage renal disease patients with secondary hyperparathyroidism who are vitamin D naive compared pre- and post doxercalciferol.
Period Title: Overall Study
STARTED	24
COMPLETED	20
NOT COMPLETED	4

Baseline Characteristics

Arm/Group Title	Pre-post Comparison
Arm/Group Description	ESRD: all patients with secondary hyperparathyroidism who are vitamin D naive doxercalciferol : 2 or 4 mcg
Overall Participants	20
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	20 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	50.4 (12.2)
Sex: Female, Male (Count of Participants)
Female	6 30%
Male	14 70%
Region of Enrollment (participants) [Number]
United States	20 100%

Outcome Measures

1. Primary Outcome

Title	Change in Endothelial Cell Function
Description	Endothelial cell function was assessed by performing flow mediated vasodilatation testing in a vascular laboratory prior to receiving doxercalciferol (either 2 mcg or 4 mcg 3 times per week at hemodialysis) and then after receiving the drug for 30 days.
Time Frame	1 month

Outcome Measure Data

Analysis Population Description

prospective open-label 30-day observational study testing the effects of doxercalciferol on mediated vasodilation (FMD) among 20 dialysis pts with secondary hyperparathyroidism

Arm/Group Title	Pre-post Comparison
Arm/Group Description	ESRD: all patients with secondary hyperparathyroidism who are vitamin D naive doxercalciferol
Measure Participants	20
Mean (Standard Deviation) [percent change in FMD]	.23 (1.4)

Adverse Events

Arm/Group Title	Pre and Post Doxicalciferol
Arm/Group Description	ESRD: all patients with secondary hyperparathyroidism who are vitamin D naive doxercalciferol 2 mcg or 4 mcg three times per week for 1 month
All Cause Mortality
	Pre and Post Doxicalciferol
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Pre and Post Doxicalciferol
	Affected / at Risk (%)	# Events
Total	1/20 (5%)
Cardiac disorders
atypical chest pain	1/20 (5%)	1
Metabolism and nutrition disorders
diabetic gastroparesis	1/20 (5%)	1
Other (Not Including Serious) Adverse Events
	Pre and Post Doxicalciferol
	Affected / at Risk (%)	# Events
Total	1/20 (5%)
Metabolism and nutrition disorders
serum phosphorus 10.4	1/20 (5%)	1

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.