The Role of Vitamin D in Immune Function in Patients With Chronic Kidney Disease (CKD) Stages 3 and 4.

Sponsor

Indiana University (Other)

Overall Status

Completed

CT.gov ID

NCT00749736

Collaborator

(none)

100

Enrollment

Location

Arms

Duration (Months)

2.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Patients with chronic kidney disease (CKD) are commonly deficient in vitamin D, with low levels of both calcidiol (25 hydroxy vitamin D) and calcitriol (1,25-hydroxy vitamin D). Patients with CKD are also known to have abnormalities in their immune cells, increased susceptibility to infection and increased prevalence of malignancies. In patients without kidney disease, repletion of vitamin D appears to help some immune mediated diseases. Thus it is logical that patients with CKD who are vitamin D deficient may benefit from repletion of vitamin D, in either its native form (cholecalciferol/ergocalciferol) or in the form of calcitriol or its analogues. However, no interventional data demonstrates that repletion positively impacts immune status in CKD patients. To test this hypothesis, a large interventional study will be required. However, prior to conducting this study, several important steps are needed. The present proposal aims to generate the necessary data to appropriately plan and conduct a future multi center interventional study. Specifically, we will examine the following specific aims in a population of CKD stage 3 and 4 subjects from Indiana University Affiliated Nephrology Clinics and determine

if abnormalities in immune cells and immune blood tests are related to abnormalities in vitamin D.
how reproducible these changes are on repeat testing and
if repletion of vitamin D changes these cells and immune blood tests in a small pilot study.

Condition or Disease	Intervention/Treatment	Phase
Chronic Kidney Disease	Dietary Supplement: cholecalciferol Dietary Supplement: doxercalciferol Dietary Supplement: placebo	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

The Role of Vitamin D in Immune Function in Patients With CKD Stages 3 and 4.

Study Start Date :

Jul 1, 2008

Actual Primary Completion Date :

Jul 1, 2012

Actual Study Completion Date :

Jul 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 1 4000 IU of cholecalciferol per day	Dietary Supplement: cholecalciferol 4000 IU of cholecalciferol per day 15 patients will be enrolled in each arm.
Active Comparator: 2 1 mcg of doxercalciferol per day.	Dietary Supplement: doxercalciferol 1 mcg of doxercalciferol per day
Placebo Comparator: 3 placebo for six months	Dietary Supplement: placebo placebo for 6 months; with stratification based on stage of CKD by modified MDRD formula. 15 patients will be enrolled in each arm.

Arm

Intervention/Treatment

Active Comparator: 1

4000 IU of cholecalciferol per day

Dietary Supplement: cholecalciferol

4000 IU of cholecalciferol per day 15 patients will be enrolled in each arm.

Active Comparator: 2

1 mcg of doxercalciferol per day.

Dietary Supplement: doxercalciferol

1 mcg of doxercalciferol per day

Placebo Comparator: 3

placebo for six months

Dietary Supplement: placebo

placebo for 6 months; with stratification based on stage of CKD by modified MDRD formula. 15 patients will be enrolled in each arm.

Outcome Measures

Primary Outcome Measures

The primary endpoint will be the change in CD4+/CD8+ ratio and other flow cytometry parameters based on the results of Aims 1 and 2, TH1/TH2 cytokine profile, and conversion from anergic to reactive skin testing. [6 months from baseline visit]

Secondary Outcome Measures

A change in mean blood pressure from one week of ambulatory measures, random protein/creatinine ratio, and differences in muscle strength by timed up and go test, and measures of quality of life using the SF36 forms. [6 months from baseline visit.]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

no administration of any form of vitamin D supplement or therapy in the last 60 days except for that in a multi vitamin
Hgb >10 mg/dl
able to sign informed consent
CKD stage 3 (GFR 30-59ml/min) or stage 4 (GFR 15-29ml/min)
iPTH <70pg/ml for stage 3 or iPTH <110pg/ml for stage 4
calcidiol levels < or +20ng/ml