Impact of Vitamin D Repletion in Hemodialysis Patients

This study has been completed.
Sponsor:
Collaborators:
National Kidney Foundation
American Heart Association
Information provided by (Responsible Party):
Anita Mehrotra MD, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:
NCT01175798
First received: August 3, 2010
Last updated: February 26, 2014
Last verified: July 2012
  Purpose

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.


Condition Intervention
Vitamin D Deficiency
End-stage Renal Disease
Drug: Cholecalciferol

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Immunologic Impact of Vitamin D Repletion in Hemodialysis Patients: A Randomized Controlled Trial

Resource links provided by NLM:


Further study details as provided by Mehrotra, Anita, M.D.:

Primary Outcome Measures:
  • Change in 25OH-Vitamin D level [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Change in immune parameters [ Time Frame: 1 year ] [ Designated as safety issue: No ]
    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.


Estimated Enrollment: 180
Study Start Date: August 2010
Study Completion Date: August 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: Vitamin D

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01175798

Locations
United States, New York
Mount Sinai School of Medicine
New York, New York, United States, 10029
Sponsors and Collaborators
Mehrotra, Anita, M.D.
National Kidney Foundation
American Heart Association
Investigators
Principal Investigator: Anita Mehrotra, MD Mount Sinai School of Medicine
  More Information

No publications provided

Responsible Party: Anita Mehrotra MD, Principal Investigator, Mount Sinai School of Medicine
ClinicalTrials.gov Identifier: NCT01175798     History of Changes
Other Study ID Numbers: 09-2275
Study First Received: August 3, 2010
Last Updated: February 26, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Mehrotra, Anita, M.D.:
Vitamin D deficiency
End-stage renal disease
Immunity

Additional relevant MeSH terms:
Kidney Diseases
Kidney Failure, Chronic
Vitamin D Deficiency
Urologic Diseases
Renal Insufficiency, Chronic
Renal Insufficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Cholecalciferol
Vitamin D
Ergocalciferols
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on July 24, 2014