End-stage Renal Disease, Vitamin D Deficiency
Conditions
Keywords
Vitamin D deficiency, End-stage renal disease, Immunity
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.
Interventions
DRUGCholecalciferol
50,000 IU PO weekly x 6 weeks
Sponsors
National Kidney Foundation, United States
American Heart Association
Mehrotra, Anita, M.D.
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 25OH-Vitamin D Level | 1 year | 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
| Measure | Time frame | Description |
|---|---|---|
| Change in Immune Parameters | 1 year | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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). | 34 |
| Vitamin D Repletion Patients will be randomized in a 3:2 ratio to oral Vitamin D treatment, or standard of care (no repletion).
Cholecalciferol: 50,000 IU PO weekly x 6 weeks | 62 |
| Total | 96 |
Baseline characteristics
| Characteristic | Total | Vitamin D Repletion | No Treatment (Standard of Care) |
|---|---|---|---|
| 25(OH) vitamin D | 13.2 ng/dL | 13.4 ng/dL | 13.1 ng/dL |
| Age, Continuous | 59 years STANDARD_DEVIATION 15 | 60.2 years STANDARD_DEVIATION 14.3 | 58.9 years STANDARD_DEVIATION 14.9 |
| Sex: Female, Male Female | 40 Participants | 26 Participants | 14 Participants |
| Sex: Female, Male Male | 56 Participants | 36 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 34 | 0 / 62 |
| serious Total, serious adverse events | 0 / 34 | 0 / 62 |
Outcome results
Primary
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.
Time frame: 1 year
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| No Treatment (Standard of Care) | Change in 25OH-Vitamin D Level | 15.8 ng/dL |
| Vitamin D Repletion | Change in 25OH-Vitamin D Level | 40.9 ng/dL |
Secondary
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.
Time frame: 1 year