Impact of Vitamin D Repletion in Hemodialysis Patients

Immunologic Impact of Vitamin D Repletion in Hemodialysis Patients: A Randomized Controlled Trial

Dialysis patients often suffer from defects in their immune system (that part of the body which fights infection). Evidence suggests that Vitamin D deficiency may have a negative effect on immunity, and many dialysis patients are deficient in Vitamin D. We believe that by giving Vitamin D to dialysis patients who are deficient, we may help improve their immune system. This study will test that idea.

Study Overview

• Status: Completed
• Conditions: Vitamin D Deficiency; End-stage Renal Disease
• Intervention / Treatment: Drug: Cholecalciferol

Detailed Description

Innate and adaptive immunity are commonly impaired in patients with end stage renal disease (ESRD) on dialysis. The myriad of immune defects in these patients, often attributed to uremia, may account for their high risk of bacterial infection and suboptimal responses to vaccination. The mechanisms underlying these abnormalities in immune function remain elusive, but emerging evidence indicates that 25OH-Vitamin D exerts potent and complex control over innate and adaptive immunity. Vitamin D deficiency is common in dialysis patients, and the immune effects associated with 25OH-Vit D deficiency overlap with those found in many dialysis patients. The kidney is the dominant site of 1-alpha-hydroxylase activity required for producing active 1,25OH-Vit D; however, immune cells also express the 1-alpha-hydroxylase enzyme. Evidence indicates the effects of Vitamin D on modulating immunity require conversion of 25OH-Vit D to 1,25OH-Vit D within the immune cells (rather than via circulating 1,25OH-Vit D). As a consequence, total body deficiency of 25OH-Vit D can impact immune function despite ongoing therapy with active 1,25OH-Vit D (which most dialysis patients are receiving). Our preliminary data confirm the high prevalence of 25OH-Vit D deficiency in dialysis patients and show that Th1 T cell alloimmunity is stronger in patients deficient in 25OH-Vit D, supporting the hypothesis that Vit D deficiency has important immunological consequences. Based on the published literature and our preliminary data, we hypothesize that repletion of 25OH-Vit D enhances immunity in dialysis patients. To test this hypothesis, we propose a randomized controlled trial of oral 25OH-Vit D repletion in this patient population. One hundred fifty 25OH-Vit D deficient study subjects will be randomized to either treatment with 50,000 IU oral 25OH-Vit D weekly or no treatment (standard of care). The primary outcome of change in 25OH-Vit D level will be measured at 6 weeks, 3 months, 6 months, and 12 months. Secondary outcomes to be measured include change in peripheral blood mononuclear cell (PBMC) profile by flow cytometry at 6 and 12 months, change in ELISPOT-based panel of reactive T cell (PRT) readout at 6 and 12 months, change in PMBC cytokine production in response to toll-like-receptor stimulation at 6 and 12 months, and response to influenza vaccination.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai 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:

1. Age > 18 years
2. Chronic hemodialysis treatments for at least 2 consecutive months
3. 25OH-Vitamin D level < 25 ng/mL (inclusion criteria for randomization)

Exclusion Criteria:

1. History of acute renal failure requiring dialysis with potential for renal recovery
2. History of HIV/AIDS
3. Inability to provide informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: No treatment (standard of care); Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion).
Experimental: Vitamin D repletion; Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion).	Drug: Cholecalciferol; 50,000 IU PO weekly x 6 weeks; Other Names: Vitamin D

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in 25OH-Vitamin D Level	Vitamin D deficient study subjects will be randomized to either treatment with 50,000 IU oral 25OH-Vit D weekly or no treatment (standard of care). The primary outcome of change in 25OH-Vit D level will be measured at 6 weeks, 3 months, 6 months, and 12 months.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Immune Parameters	Secondary outcomes to be measured include change in peripheral blood mononuclear cell (PBMC) profile by flow cytometry at 6 and 12 months, change in ELISPOT-based panel of reactive T cell (PRT) readout at 6 and 12 months, change in PMBC cytokine production in response to toll-like-receptor stimulation at 6 and 12 months, and response to influenza vaccination.	1 year

Collaborators and Investigators

• Sponsor: Mehrotra, Anita, M.D.
• Collaborators: American Heart Association; National Kidney Foundation
• Investigators: Principal Investigator: Anita Mehrotra, MD, Icahn School of Medicine at Mount Sinai

Publications and helpful links

General Publications

• Li L, Lin M, Krassilnikova M, Ostrow K, Bader A, Radbill B, Uribarri J, Tokita J, Leisman S, Lapsia V, Albrecht RA, Garcia-Sastre A, Branch AD, Heeger PS, Mehrotra A. Effect of cholecalciferol supplementation on inflammation and cellular alloimmunity in hemodialysis patients: data from a randomized controlled pilot trial. PLoS One. 2014 Oct 8;9(10):e109998. doi: 10.1371/journal.pone.0109998. eCollection 2014.

Study record dates

Study Major Dates

• Study Start: August 1, 2010
• Primary Completion (Actual): August 1, 2013
• Study Completion (Actual): August 1, 2013

Study Registration Dates

• First Submitted: August 3, 2010
• First Submitted That Met QC Criteria: August 3, 2010
• First Posted (Estimate): August 5, 2010

Study Record Updates

• Last Update Posted (Estimate): September 22, 2014
• Last Update Submitted That Met QC Criteria: September 15, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: End-stage renal disease; Immunity; Vitamin D deficiency
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Nutrition Disorders; Avitaminosis; Deficiency Diseases; Malnutrition; Renal Insufficiency, Chronic; Kidney Diseases; Vitamin D Deficiency; Kidney Failure, Chronic; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 09-2275