Assessment of Vitamin D Supplementation and Immune Function

Study Overview
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Brief Summary
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Hypothesis: Volunteers with vitamin D insufficiency (serum 25(OH)D 25-50 nmol/L) given intermediate or high dose vitamin D supplements (2,000 or 5,000 IU per day) will have increased production of anti-bacterial peptides and interleukin-1, decreased production of other pro-inflammatory cytokines, increased production of regulatory cytokines and an enhanced T- and B-cell response to a tetanus vaccine compared to vitamin D insufficient subjects given low dose vitamin D supplements (400 IU per day).

Detailed Description
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Specific Aim 1: Determine if high dose vitamin D supplements decrease the production of proinflammatory and increase the production of regulatory cytokines and chemokines by innate immune cells stimulated ex vivo. Specific Aim 2: Determine if high dose vitamin D supplements decrease serum markers of inflammation and increase serum and cellular levels of defensive molecules (e.g., cathelicidin). Specific Aim 3: Determine if high dose vitamin D supplements decrease blood levels of proinflammatory T-helper type 1 (Th1) and Th17 cells and increase levels of anti-inflammatory T-regulatory (Treg) and Th2 cells. Specific Aim 4: Determine if high dose vitamin D supplements increase antigen specific T cell and B cell responses after tetanus vaccination.

Official Title
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Assessment of Vitamin D Supplementation and Immune Function

Conditions
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Vitamin D Deficiency

Intervention / Treatment
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* Dietary Supplement: Vitamin D - Treatment 1
* Dietary Supplement: Vitamin D - Treatment 2
* Dietary Supplement: Vitamin D - Treatment 3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 20-49 (men) and 20-45 (women) BMI 18.5-30 Serum 25OH Vitamin D 25-50 nmol/L Exclusion Criteria: Pregnant or nursing women Daily smoker Anemia (Hgb<12 mg/dL for women and <13 mg/dL for men) determined at initial visit Any report or diagnosis of disease or chronic condition that may affect vitamin D absorption such as cystic fibrosis, celiac disease, surgical removal of part of the stomach or intestines, and some forms of liver disease Diagnosis of hyper parathyroidism and chronic granulomatous disease, which increases risk of hypercalcemia. Planned to travel to a location at which either altitude or latitude would result in significant vitamin D synthesis during the study period. Not previously vaccinated with TT, or vaccinated within five years Use of steroids or antibiotics within the past 4 weeks Current use of nutritional supplements that may alter immune function such as omega 3 fatty acid supplements Current use of anti-inflammatory or anti-convulsion medications Self reported history of significant adverse response to previous vaccinations

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D - Treatment 1<br>400 IU/day Vitamin D | Dietary Supplement: Vitamin D - Treatment 1<br>* Volunteers will take a 400 IU/day dose of Vitamin D for 12 weeks.<br>|
| Experimental: Vitamin D- Treatment 2<br>2,000 IU/day Vitamin D | Dietary Supplement: Vitamin D - Treatment 2<br>* Volunteers will take a 2,000 IU/day dose of Vitamin D for 12 weeks.<br>|
| Experimental: Vitamin D- Treatment 3<br>5,000 IU/day Vitamin D | Dietary Supplement: Vitamin D - Treatment 3<br>* Volunteers will take a 5,000 IU/day dose of Vitamin D for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cathelicidin levels in granulocytes |  | 0, 8, and 12 weeks | 
| Change in cytokine levels from stimulated Periferal Blood Mononuclear Cells |  | 0, 8 and 12 weeks | 
| Change in serum cytokines and acute phase proteins |  | 0, 8 and 12 weeks | 
| Change in markers of response to tetanus vaccination | Markers of response to tetanus vaccine include tetanus-specific proliferation and production of cytokines by CD4 T-helper cells. | 0, 8, 9, 10 and 12 weeks | 
| Change in serum 25OH Vitamin D |  | 0, 4, 8, and 12 weeks | 
| Change in urinary calcium-to-creatinine ratio |  | 0, 2, 4, 6, 8 and 10 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in level of 5-lipoxygenase protein in granulocytes |  | 0, 8 and 12 weeks | 
| Change in production of leukotrienes in granulocytes |  | 0, 8, and 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Vitamin D, Immune function