Effect of Vitamin D Replacement on Immune Function and Cognition in MS Patients

Study Overview
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Brief Summary
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Assessing the immune activation in MS patients deficient in Vitamin D and whether Vitamin D supplementation reverse the immune activation Evaluating whether Vitamin D deficiency result in lower cognitive performance in MS patients and the effect of Vitamin D supplementation on reversing the cognitive impairment?

Detailed Description
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We will compare the immune responses in patients with Vitamin D deficiency (serum level <20ng/ml) to those of patients with normal Vitamin D (serum level >35 ng/ml). We will focus on proliferation and cytokine production to myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) peptides and on the percentage of Th1 (IFN gamma producing cells) and Th17 (IL-17 producing cells) during in vitro polarization assays. Our hypothesis is that patients with low Vitamin D have increase proliferation to MBP and MOG and increased production of pro-inflammatory cytokines (IFN gamma and IL-17) and that Vitamin D supplementation will decrease this pro-inflammatory profile. We will measure cognitive performance in patients with Vitamin D deficiency (serum level <20ng/ml) compared to those of patients with normal Vitamin D (serum level >35 ng/ml) after adjusting for educational levels and disease duration. We hypothesize that low Vitamin D has a negative effect on cognitive performance and that Vitamin D supplementation will improve cognitive function.

Official Title
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Effect of Vitamin D Replacement on Immune Function and Cognition in MS Patients

Conditions
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Multiple Sclerosis (MS)

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Definite diagnosis of Multiple Sclerosis following the revised McDonald MS diagnostic criteria Male and Female Aged 18 and above On interferon-β treatment (Rebif®, Avonex®, or Betaseron®) No signs of active inflammation or attack or new lesions on MRI Exclusion Criteria: Treatment with immune modulating/ suppressive drugs other than IFN-b within 6 weeks prior to enrolment Pregnancy Hypercalcemia eglomerular filtration rate<60 History of primary hyperparathyroidism, hypercalcemia, renal dysfunction, cardiac disease, malignancy, or granulomatous disease The occurrence of an exacerbation (defined as an episode of neurologic dysfunction lasting at least 24 hours) within 4 weeks of enrollment History of dementia or related disorders History of traumatic brain injury Diagnosis of epilepsy or history of seizure Diagnosis of psychiatric disease, substance abuse/dependence, alcohol abuse/dependence Currently, on any of the following medications Lithium, or Thiazide diuretics

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| vitamin D deficient,<br>Vitamin D deficiency (serum level <20ng/ml) | |
| Vitamin D normal<br>Serum level >35 ng/ml | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Is there evidence of immune activation in MS patients deficient in Vitamin D and does Vitamin D supplementation reverse the immune activation? | We will compare the immune responses in patients with Vitamin D deficiency (serum level <20ng/ml) to those of patients with normal Vitamin D (serum level >35 µg/ml). We will focus on proliferation and cytokine production to myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) peptides and on the percentage of Th1 (IFN gamma producing cells) and Th17 (IL-17 producing cells) during in vitro polarization assays. Our hypothesis is that patients with low Vitamin D have increase proliferation to MBP and MOG and increased production of pro-inflammatory cytokines (IFN gamma and IL-17) and that Vitamin D supplementation will decrease this pro-inflammatory profile. | 3months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Does Vitamin D deficiency result in lower cognitive performance in MS patients and does Vitamin D supplementation reverse the cognitive impairment? | We will measure cognitive performance in patients with Vitamin D deficiency (serum level <20ng/ml) compared to those of patients with normal Vitamin D (serum level >35 ng/ml) after adjusting for educational levels and disease duration. We hypothesize that low Vitamin D has a negative effect on cognitive performance and that Vitamin D supplementation will improve cognitive function. | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis (MS)