Impact of Vitamin A Supplementation on Immune System in Multiple Sclerosis Patients

Study Overview
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Brief Summary
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The aim of this study is to study the comparison between the effects of supplementation with 25000 IU preformed vitamin A (retinyl palmitate) or placebo for 6 months on immune system and Th1/Th2 balance in patients with Multiple Sclerosis.

Detailed Description
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Multiple Sclerosis (MS) is a chronic inflammatory disease where Th1 like responses from myelin-specific CD4+ T cells, as secretion of pro-inflammatory IFN-g, are believed to play a major role in the pathogenesis. The myelin-specific T cells that mediate tissue destruction in MS are believed to become activated outside the central nervous system (CNS) in lymphoid tissue and when they cross the blood brain barrier they will re-encounter their antigen. Immune deviation is the redirection of the immune response from most often Th1 like responses to Th2 like responses, even though the opposite can also occur. Vitamin A (VA) or VA-like analogs known as retinoids, are potent hormonal modifiers of type 1 or type 2 responses but a definitive description of their mechanism(s) of action is lacking. High level dietary vitamin A enhances Th2 cytokine production and IgA responses, and is likely to decrease Th1 cytokine production. Retinoic acid inhibits IL 12 production in activated macrophages, and RA pretreatment of macrophages reduces IFNγ production and increases IL4 production in antigen primed CD4 T cells. Supplemental treatment with vitamin A or retinoic acid (RA) decreases IFNγ and increases IL5, IL10, and IL4 production. Thus, vitamin A deficiency biases the immune response in a Th1 direction, whereas high level dietary vitamin A may bias the response in a Th2 direction.

Official Title
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The Study of the Effects of Vitamin A Supplementation on Immune System and Th1/Th2 Balance in Patients With Multiple Sclerosis

Conditions
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Relapsing Remitting Multiple Sclerosis

Intervention / Treatment
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* Dietary Supplement: Vitamin A
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have used interferon beta in last 3 months. Patients with 1-5 EDSS Exclusion Criteria: Patients who have diseases which affect on Th1/Th2 balance such as asthma, active viral infections, and autoimmune diseases, OR Patients who have allergy to vitamin A compounds, OR Patients who have used vitamin supplements in last 3 months.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 45 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: with Multiple Sclerosis/ vitamin A<br>Patients with MS confirmed Relapsing Remitting Type who receive 25000 IU/day vitamin A | Dietary Supplement: Vitamin A<br>* 25000 IU/day (one capsule per day) Vitamin A for 6 months<br>* Other names: Retinyl palmitate;|
| Placebo Comparator: with Multiple Sclerosis/ placebo<br>Patients with Multiple Sclerosis confirmed Relapsing Remitting Type who receive 1 cap of placebo per day | Drug: Placebo<br>* 1 capsule per day for six months<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference Serum Levels of High-sensitive C-reactive Protein (Hs-CRP), Before and After of Supplementation |  | first day and after 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference of IL-4 Levels in Supernatant of Peripheral Blood Mononucleated Cells (PBMCs) Stimulated With Phytohemagglutinin (PHA), Before and After of Supplementation |  | first day and after 6 month | 
| Difference of Retinol Binding Protein (RBP) / Transthyretin (TTR) Ratio, (Difference of RBP/ TTR Ratio), Before and After of Supplementation |  | first day and after 6 month | 
| Peripheral Blood Mononucleated Cells (PBMCs) Proliferation Assay (BrdU Colorimetric) | difference of PBMCs proliferation stimulated with myelin oligodendrocyte glycoprotein (MOG), before and after of supplementation | first day and after 6 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multiple Sclerosis, Vitamin A, CD4-Positive T-Lymphocytes, Th1 Cells, Th2 Cells