TY - JOUR
T1 - Dose-related effects of vitamin D on immune responses in patients with clinically isolated syndrome and healthy control participants
T2 - Study protocol for an exploratory randomized double- blind placebo-controlled trial
AU - O'Connell, Karen
AU - Kelly, Siobhan
AU - Kinsella, Katie
AU - Jordan, Sinead
AU - Kenny, Orla
AU - Murphy, David
AU - Heffernan, Eric
AU - O'Laoide, Risteard
AU - O'Shea, Donal
AU - McKenna, Carmel
AU - Cassidy, Lorraine
AU - Fletcher, Jean
AU - Walsh, Cathal
AU - Brady, Jennifer
AU - McGuigan, Christopher
AU - Tubridy, Niall
AU - Hutchinson, Michael
PY - 2013/8/27
Y1 - 2013/8/27
N2 - 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/Design: 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.Trial registration: EU Clinical Trials Register: EudraCT: 2012-000635-68. ClinicalTrials.gov identifier: NCT01728922.
AB - 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/Design: 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.Trial registration: EU Clinical Trials Register: EudraCT: 2012-000635-68. ClinicalTrials.gov identifier: NCT01728922.
KW - Cholecalciferol
KW - Clinical trial
KW - Clinically isolated syndrome
KW - Immunomodulation
KW - Multiple sclerosis
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=84883094436&partnerID=8YFLogxK
U2 - 10.1186/1745-6215-14-272
DO - 10.1186/1745-6215-14-272
M3 - Article
C2 - 23981773
AN - SCOPUS:84883094436
SN - 1745-6215
VL - 14
SP - 272
JO - Trials
JF - Trials
IS - 1
M1 - 272
ER -
