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

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

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

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

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease
• Intervention / Treatment: Dietary supplement: cholecalciferol; Dietary supplement: doxercalciferol; Dietary supplement: placebo

• Study Type: Interventional
• Enrollment (Actual): 100
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Exclusion Criteria:

• initial corrected Calcium >9.7mg/dl
• initial serum Phosphorus >5.0mg/dl
• initial standardized blood pressure of >160/100
• history of significant liver disease or cirrhosis
• anticipated requirement for dialysis in 6 months
• malabsorption, severe chronic diarrhea, or ileostomy
• no calcimimetic or active vitamin D therapy 60 days prior to enrollment

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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

Outcome Measure	Time Frame
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.

Collaborators and Investigators

• Sponsor: Indiana University
• Investigators: Principal Investigator: Sharon M Moe, MD, Indiana University School of Medicine

Study record dates

Study Major Dates

• Study Start: July 1, 2008
• Primary Completion (Actual): July 1, 2012
• Study Completion (Actual): July 1, 2012

Study Registration Dates

• First Submitted: September 8, 2008
• First Submitted That Met QC Criteria: September 8, 2008
• First Posted (Estimate): September 9, 2008

Study Record Updates

• Last Update Posted (Estimate): March 29, 2013
• Last Update Submitted That Met QC Criteria: March 28, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Keywords: normal; immune system; vitamin D; variability; measures; determine; intrapatient; interpatient
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; 1 alpha-hydroxyergocalciferol
• Other Study ID Numbers: 0707-04