Clinical trial NCT00677534: Role of Extrarenal 1-Alpha-Hydroxylase in Patients With End Stage Renal Disease
Official title: Exploring the Role of Extrarenal 1-Alpha-Hydroxylase in Patients With End Stage Renal Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: End-Stage Renal Disease
Keywords: Endstage renal disease
Vitamin D
Monocyte function
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2008-05-14
Enrollment: 7
Sex: ALL
Minimum age (years): 21
Maximum age (years): 88
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Monocyte VDR Expression With Vitamin D Therapy
timeFrame: Change from End of Washout to Week 12
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: University of Kansas Medical Center
name: Jason Stubbs, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Stubbs JR, Idiculla A, Slusser J, Menard R, Quarles LD. Cholecalciferol supplementation alters calcitriol-responsive monocyte proteins and decreases inflammatory cytokines in ESRD. J Am Soc Nephrol. 2010 Feb;21(2):353-61. doi: 10.1681/ASN.2009040451. Epub 2009 Dec 10.