Clinical trial NCT01225289: Impact of Vitamin A Supplementation on Immune System in Multiple Sclerosis Patients
Official title: The Study of the Effects of Vitamin A Supplementation on Immune System and Th1/Th2 Balance in Patients With Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Relapsing Remitting Multiple Sclerosis
Keywords: Multiple Sclerosis
Vitamin A
CD4-Positive T-Lymphocytes
Th1 Cells
Th2 Cells
Lead sponsor: Tehran University of Medical Sciences
Sponsor class: OTHER
First posted: 2010-10-21
Enrollment: 36
Sex: ALL
Minimum age (years): 20
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Difference Serum Levels of High-sensitive C-reactive Protein (Hs-CRP), Before and After of Supplementation
timeFrame: first day and after 6 month
Secondary outcomes:
measure: Difference of IL-4 Levels in Supernatant of Peripheral Blood Mononucleated Cells (PBMCs) Stimulated With Phytohemagglutinin (PHA), Before and After of Supplementation
timeFrame: first day and after 6 month
measure: Difference of Retinol Binding Protein (RBP) / Transthyretin (TTR) Ratio, (Difference of RBP/ TTR Ratio), Before and After of Supplementation
timeFrame: first day and after 6 month
measure: Peripheral Blood Mononucleated Cells (PBMCs) Proliferation Assay (BrdU Colorimetric)
timeFrame: first day and after 6 month
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Tehran University of Medical Sciences, School of Public Health Tehran, Tehran, Iran, Islamic Republic o
city: Tehran
country: Iran, Islamic Republic of
facility: Tehran University of Medical Sciences, School of Public Health
Study officials:
affiliation: Tehran University of Medical Sciences
name: Ali Akbar Saboor Yaraghi, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Tehran University of Medical Sciences
name: Sima Jafarirad, PhD student
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mohammadzadeh Honarvar N, Harirchian MH, Koohdani F, Siassi F, Abdolahi M, Bitarafan S, Salehi E, Sahraian MA, Eshraghian MR, Saboor-Yarghi AA. The effect of vitamin A supplementation on retinoic acid-related orphan receptor gammat (RORgammat) and interleukin-17 (IL-17) gene expression in Avonex-treated multiple sclerotic patients. J Mol Neurosci. 2013 Nov;51(3):749-53. doi: 10.1007/s12031-013-0058-9. Epub 2013 Jul 19.