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

University College Dublin64 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Clinically Isolated Syndrome Multiple Sclerosis

Interventions

5000IU vitamin DDIETARY_SUPPLEMENT

Vigantol Oil

10000IU vitamin DDIETARY_SUPPLEMENT

Vigantol Oil

PlaceboOTHER

Placebo Oil

Eligibility

Sex: ALLMin age: 18 YearsMax age: 55 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (1)

St Vincent's University Hospital

Dublin, Dublin 4, Ireland

Outcomes

Primary Outcomes

The effects of two doses of vitamin D and placebo therapy on the change in the frequency of CD4 T cell subsets and cytokine responses of PBMC over 24 weeks of therapy from baseline.

A number of measures will be examined in particular IL-10 production and the frequency of Th17 cells.

Time frame: This outcome measure will be assessed at baseline and at 24 weeks.

Secondary Outcomes

The number of new T2 and gadolinium enhancing lesions compared to baseline amongst the study group.

The MRI out-come measure will assess the a) number of Gadolinium enhancing lesions b) the number of new and enlarging T2 lesions c) the combined unique lesion count (new and enlarging T2 lesions plus Gadolinium enhancing lesions) after 24 weeks of therapy in the three arms, 5000IU, 10,000IU vitamin D and placebo . Mean and median new T2 and gadolinium-enhancing lesions at 24 weeks (end of the trial) will be compared for each treatment allocation group. In addition the mean and median number of new T2 lesions plus gadolinium enhancing lesions in all the CIS patients on vitamin D will be compared to the mean and median in the placebo group.

Time frame: Baseline and 24 weeks

Relapse occurrence in the CIS patients during 24 weeks of the trial

Relapse occurrence in the CIS patients during 24 weeks of the trial;(i) annualised relapse rates (ARR), (ii) percentage of patients free from relapses and (iii) time to first relapse will be compared for each treatment allocation group. In addition the same relapse measures will be applied to both vitamin D treated groups combined and compared to those in the placebo group.

Time frame: At each clinic visit or as the need arises.

The percentage of CIS patients in each treatment arm free from any evidence of disease activity (No relapses, no new T2 lesions, no gadolinium enhancing lesions).

Time frame: At 24 weeks.

Data from ClinicalTrials.gov

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