title: Dose-related effects of vitamin D on immune responses in patients with clinically isolated syndrome and healthy control participants: study protocol for an exploratory randomized double- blind placebo-controlled trial.
abstract: BACKGROUND
  There is increasing evidence linking vitamin D deficiency to both susceptibility to, and severity of, multiple sclerosis (MS). Patients with the clinically isolated syndrome represent the initial presentation of a demyelinating disorder, and those with asymptomatic lesions on magnetic resonance imaging (MRI) are at risk of progression to clinically definite MS. The aims of this study are to examine the immunologic effects of vitamin D in both healthy individuals and in patients with clinically isolated syndrome, and in the latter group the effects on disease progression assessed by MRI and clinical measures.
  
  
  METHODS
  This is a single-center double-blind randomized placebo-controlled clinical trial. The primary endpoint is the immunologic effects of two doses of vitamin D compared with placebo over 24 weeks in both healthy control participants and patients presenting with the clinically isolated syndrome. Healthy control participants (n = 39) and patients with clinically isolated syndrome (n = 45) will be randomized to one of three arms, namely 1) vitamin D 5,000 IU daily, 2) vitamin D 10,000 IU daily, or 3) placebo, and followed up for 24 weeks. In both patients and healthy control participants, the primary outcome will be immunologic measures of the frequency of CD4 T-cell subsets and cytokine responses in peripheral blood mononuclear cells, assessed at baseline, and after 16 and 24 weeks of treatment. Secondary endpoints, in the patients with clinically isolated syndrome, will be relapse activity, and the number of new T2 lesions and gadolinium-enhancing lesions assessed by MRI in the two vitamin D-treated groups compared with the placebo-treated group over the 24 weeks of the study.
  
  
  BACKGROUND
  EU Clinical Trials Register: EudraCT: 2012-000635-68. ClinicalTrials.gov identifier: NCT01728922.
authors: Department of Neurology, St Vincent's University Hospital, Elm Park, Dublin 4, Ireland. k.oconnell@st-vincents.ie.
authors: Karen
authors: K
authors: O'Connell
authors: Siobhan
authors: S
authors: Kelly
authors: Katie
authors: K
authors: Kinsella
authors: Sinead
authors: S
authors: Jordan
authors: Orla
authors: O
authors: Kenny
authors: David
authors: D
authors: Murphy
authors: Eric
authors: E
authors: Heffernan
authors: Risteard
authors: R
authors: O'Laoide
authors: Donal
authors: D
authors: O'Shea
authors: Carmel
authors: C
authors: McKenna
authors: Lorraine
authors: L
authors: Cassidy
authors: Jean
authors: J
authors: Fletcher
authors: Cathal
authors: C
authors: Walsh
authors: Jennifer
authors: J
authors: Brady
authors: Christopher
authors: C
authors: McGuigan
authors: Niall
authors: N
authors: Tubridy
authors: Michael
authors: M
authors: Hutchinson
mesh_terms: D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000187:drug effects / Q000473:pathology; D018791:CD4 Lymphocyte Count; D002762:Cholecalciferol / Q000008:administration & dosage*; D002985:Clinical Protocols; D016207:Cytokines / Q000097:blood; D003711:Demyelinating Diseases / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D018450:Disease Progression; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D064368:Healthy Volunteers; D006801:Humans; D007494:Ireland; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology; D008279:Magnetic Resonance Imaging; D009103:Multiple Sclerosis / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome; D014807:Vitamin D / Q000008:administration & dosage*
chemical_list: D015415:Biomarkers; D016207:Cytokines; D014807:Vitamin D; D002762:Cholecalciferol
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