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

Study Overview
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Brief Summary
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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.

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

Conditions
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Chronic Kidney Disease

Intervention / Treatment
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* Dietary Supplement: cholecalciferol
* Dietary Supplement: doxercalciferol
* Dietary Supplement: placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vitamin D, determine, normal, intrapatient, interpatient, variability, measures, immune system