Impact of Vitamin D Repletion in Hemodialysis Patients

NCT ID: NCT01175798

Last Updated: 2014-09-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-08-31
• Study Completion Date: 2013-08-31

Brief Summary

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.

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.

Conditions

Vitamin D Deficiency; End-stage Renal Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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).

Group Type: NO_INTERVENTION

No interventions assigned to this group

Vitamin D repletion

Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion).

Group Type: EXPERIMENTAL

Cholecalciferol

Intervention Type: DRUG

50,000 IU PO weekly x 6 weeks

Interventions

Cholecalciferol

50,000 IU PO weekly x 6 weeks

Intervention Type: DRUG

Other Intervention Names

Vitamin D

Eligibility Criteria

Inclusion Criteria

1. Age > 18 years

2. Chronic hemodialysis treatments for at least 2 consecutive months

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Kidney Foundation, United States

OTHER

Sponsor Role: collaborator

American Heart Association

OTHER

Sponsor Role: collaborator

Mehrotra, Anita, M.D.

INDIV

Sponsor Role: lead

Responsible Party

Anita Mehrotra MD

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Anita Mehrotra, MD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Mount Sinai School of Medicine

New York, New York, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 25296334 (View on PubMed)

Other Identifiers

09-2275

Identifier Type: -

Identifier Source: org_study_id