Role of Extrarenal 1-Alpha-Hydroxylase in Patients With End Stage Renal Disease

Not Applicable

Completed

• Conditions: End-Stage Renal Disease
• Interventions: Drug: Cholecalciferol

• Registration Number: NCT00677534
• Lead Sponsor: University of Kansas

Brief Summary

The goal of this study is to evaluate the role of nutritional Vitamin D deficiency as a potential contributor to the morbidity witnessed in patients with end-stage renal disease

Detailed Description

The goals of this study are to elucidate the function of extrarenal 1 alpha-hydroxylase activity in the setting of renal failure and to evaluate the role of nutritional vitamin D deficiency as a potential contributor to monocyte-associated inflammatory pathways in patients with end-stage renal disease (ESRD). This study will consist of patients on chronic maintenance hemodialysis three times per week who have been identified to have nutritional vitamin D deficiency. After consent for study enrollment, patients will undergo a 4 week washout period of all active vitamin D supplementation. After washout is complete, an blood sample will be obtained for baseline 25(OH)D levels and monocyte isolation for analysis by flow cytometry. Patients will then be started on cholecalciferol 50,000 IU twice weekly for 8 weeks. 25-vitamin D levels will be monitored midway through the treatment phase of the study and dosing adjusted as further described in detail within the protocol section. An additional blood sample will be drawn post-therapy for repeat 25(OH)D levels and monocyte isolation for flow cytometry analysis.

Study Timeline

• Study Start: 2008-05
• Study First Submitted: 2008-05-12
• Study First Submitted QC: 2008-05-13
• Study First Posted: 2008-05-14
• Primary Completion: 2009-08
• Study Completion: 2009-08
• Results First Submitted: 2012-06-11
• Results First Submitted QC: 2014-01-30
• Results First Posted: 2014-03-21
• Status Verified: 2014-04
• Last Update Submitted: 2014-04-10
• Last Update Posted: 2014-04-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 7

Inclusion Criteria

• End-stage renal disease undergoing maintenance hemodialysis at KUMC outpatient hemodialysis unit
• Dialysis vintage of at least 6 months duration
• Nutritional vitamin D deficiency, defined as 25(OH)D <25 ng/ml
• Age 21 to 88 years

Exclusion Criteria

• Active infection
• Recent hospitalization for acute illness (within last 1 month)
• Refusal to study participation
• Poorly controlled secondary hyperparathyroidism (iPTH>500)
• History of chronic inflammatory disease process, such as inflammatory bowel, rheumatoid arthritis, lupus, etc.
• Cinacalcet therapy
• Previous allergy to ergocalciferol
• History of parathyroidectomy
• Current treatment with immunosuppressant medications
• Noncompliance with prescribed hemodialysis regimen (i.e. skipping treatments, ending sessions early)
• Functional renal transplant within the last five years

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
1	Cholecalciferol	Cholecalciferol (Vitamin D)

Primary Outcome Measures

Name	Time	Method
Change in Monocyte VDR Expression With Vitamin D Therapy	Change from End of Washout to Week 12	Monocytes will be analyzed pre- and post-cholecalciferol by flow cytometry to measure changes in monocyte VDR expression. Unit of measure is represented by mean florescence intensity (MFI), which is a relative measure.