Pharmacokinetics of Vitamin D in Multiple Sclerosis and in Health

Study Overview
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Brief Summary
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This is a pilot study of oral vitamin D supplementation to determine if patients with Multiple Sclerosis (MS) and healthy individuals attain a similar increase in serum 25-hydroxyvitamin D levels. The investigators will also assess whether the immunologic or relevant gene expression response to oral vitamin D supplementation differs in patients with MS and healthy controls.

Official Title
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Pharmacodynamic and Immunologic Effects of Vitamin D Supplementation in Patients With Multiple Sclerosis and Healthy Controls

Conditions
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Multiple Sclerosis, Relapsing-remitting

Intervention / Treatment
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* Dietary Supplement: Vitamin D3


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female Healthy or multiple sclerosis Aged 18 to 60 Body mass index is between 18 kg/m2 and 30 kg/m2 Screening 25-hydroxyvitamin D level ≤ 75 nmol/L (30 ng/mL) White race Non-Hispanic ethnicity Willing to use birth control during study Willing to not use tanning bed during study If subject has multiple sclerosis: Relapsing-remitting MS, as defined by McDonald 2005 criteria Screening Expanded Disability Status Scale score ≤ 3.0 Using no medication for MS, or taking Copaxone, (glatiramer acetate), interferons, or natalizumab Exclusion Criteria: Pregnant or nursing Taking multivitamin & unwilling to remain off it during study Taking cod liver oil & unwilling to remain off it during study On a fat-restricted diet History of renal disease or nephrolithiasis (kidney stones) History of liver disease Taking thiazide diuretics History of hyperthyroidism History of infection with Mycobacterium species History of sarcoidosis History of cancer History of cardiac disease History of HIV History of gastrointestinal disorder Taking medications that interfere with gastrointestinal absorption Cigarette smoker in past month Use of illicit drugs in past month Use of steroids in past month History of hypercalcemia, and screening serum calcium ≤ 10 mg/dL (UCSF) or ≤ 10.7 mg/dL (Johns Hopkins) History of hypercalciuria Evidence of anemia (Hgb <11.0 g/dL) History of other serious medical conditions Taking medications that involve the P450 system or may interact with vitamin D (digoxin, diltiazem, verapamil, cimetidine, heparin, or low-molecular weight heparin) Other concerns about safety from the perspective of the treating physician If subject has MS: -History of major heat sensitivity (leading to sun-avoidant behaviors)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Female

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: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Vitamin D3<br>Both those with MS and healthy controls will be given vitamin D3 5000 IU/day by mouth for 90 days. | Dietary Supplement: Vitamin D3<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Serum Level of 25-hydroxyvitamin D | Generalized estimating equations (GEE) with an autoregressive with lag one correlation matrix were used to compare the serially-measured serum 25(OH)D levels between MS patients and Healthy Controls (HCs) to take into account repeated measures and within-subject correlations. | Baseline to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Percentages of T Cell Subsets (IFNγ+ and IL-17+) | Analyzed the mean percentage change in IFNγ+ and IL-17+ cluster of differentiation 4 (CD4) + cells (post- versus pre- supplementation). This represents a change between two time points (90 days versus baseline). | Baseline, 90 days | 
| Gene Expression Microarray | We had initially planned to do whole blood gene expression. The experience gained by the laboratory that was to perform this since the original trial was planned was that this measure is too noisy and would not yield meaningful results. Thus, this analysis will no longer be conducted. | 90 days | 
| Change in Cytokine Levels | The original plan had been to measure the change in basic serum cytokine levels (e.g. IL-17, interferon gamma; IL-10; pg/microliter). However, due to emerging data suggesting low utility of these measures, this plan was abandoned. | 90 days | 
| Change in Percentage of B Cells | The change in percentage (day 90-baseline) was originally planned for study. Due to the limited number of patients with samples this plan was abandoned. | 90 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple sclerosis, Healthy controls, Pharmacokinetics, Vitamin D