Dose-related Effects of Vitamin D3 on Immune Responses in Patients With Clinically Isolated Syndrome

Dose-related Effects of Vitamin D3 on Immune Responses in Patients With Clinically Isolated Syndrome and Healthy Control Participants. An Exploratory Double Blind Placebo Randomised Controlled Study.

The primary purpose of this study is to assess the immune response to vitamin D supplementation at two doses (5,000 IU and 10,000 IU daily) in both healthy controls and patients with clinically isolated syndrome compared to placebo. Secondary endpoints include (1) disease outcome in the clinically isolated syndrome in terms of clinical relapses and evidence of new lesions on MRI (McDonald's MS), 2) Safety of doses used

Primary endpoint: To determine the effects of vitamin D supplementation at two doses a) 5,000 IU daily b) 10,000 IU daily compared to c) placebo a 24 weeks period on the change from baseline in frequency of CD4 T cell subsets and cytokine responses by peripheral blood mononuclear cells in 1) patients with the clinically isolated syndrome. 2) healthy control participants.

Secondary endpoints:

1. To determine whether there is a dose response effect of supplementation using 5,000 IU and 10,000 IU of vitamin D versus placebo over 24 weeks on the change from baseline in the frequency of CD4 T cell subsets and cytokine responses by PBMC in 1) patients with the clinically isolated syndrome (CIS) 2) healthy control participants
2. To establish whether there is a clinical response to vitamin D measured by a) change in the number of T2 lesions and Gadolinium enhancing lesions on MRI scanning at 24 weeks compared to baseline b) reduction in relapses over 24 weeks in treated (both 5,000 IU and 10,000 IU) CIS patients versus CIS patients receiving placebo.

Inclusion Criteria: To be eligible for inclusion, each subject must meet each of the following criteria at Screening (Visit 1) and must continue to fulfil these criteria at Baseline (Visit 2).

• CIS: Patients with a clinically isolated syndrome with onset relapse within the previous three months and two or more than two asymptomatic T2 lesions on MRI brain scan.
• Aged 18-55yrs.
• Not receiving any disease modifying therapy.

Exclusion Criteria:

• Patients in whom any disease other than demyelination could explain their signs and symptoms.
• Participants with known disease of the parathyroids, a history of vitamin D intolerance, sarcoidosis, a history of hypercalcaemia of any cause.
• Participants with a baseline abnormality in serum urea, creatinine, calcium, parathormone.
• Participants on thiazide diuretics (hypercalcaemia risk).
• Patients with occurrence of a relapse less than six weeks prior to entry to study.
• Previous treatment with beta-interferons or glatiramer acetate or steroids in the last three months.
• Any previous treatment with mitoxantrone or other immunosuppressant.
• Participants already taking supplemental vitamin D.