Clinical trial NCT01175798: Impact of Vitamin D Repletion in Hemodialysis Patients
Official title: Immunologic Impact of Vitamin D Repletion in Hemodialysis Patients: A Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vitamin D Deficiency
End-stage Renal Disease
Keywords: Vitamin D deficiency
End-stage renal disease
Immunity
Lead sponsor: Mehrotra, Anita, M.D.
Sponsor class: INDIV
Collaborators: name: National Kidney Foundation, United States
name: American Heart Association
First posted: 2010-08-05
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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

Primary outcomes:
measure: Change in 25OH-Vitamin D Level
timeFrame: 1 year
Secondary outcomes:
measure: Change in Immune Parameters
timeFrame: 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Anita Mehrotra, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.