Clinically Isolated Syndrome, Multiple Sclerosis
Conditions
Keywords
Clinically isolated syndrome, Multiple sclerosis, Vitamin D, Immune response, CD4 T cell subsets, Cytokine
Brief summary
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
Detailed description
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.
Interventions
DIETARY_SUPPLEMENT5000IU vitamin D
Vigantol Oil
DIETARY_SUPPLEMENT10000IU vitamin D
Vigantol Oil
OTHERPlacebo
Placebo Oil
Sponsors
University of Dublin, Trinity College
St Vincent's University Hospital, Ireland
University College Dublin
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
similar appearance of placebo and active drug
Intervention model description
double-blind, dose ranging, two doses of vitamin D, randomised parallel groups with placebo arms in clinically isolated syndrome and heathy control participants
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | This outcome measure will be assessed at baseline and at 24 weeks. | A number of measures will be examined in particular IL-10 production and the frequency of Th17 cells. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The number of new T2 and gadolinium enhancing lesions compared to baseline amongst the study group. | Baseline and 24 weeks | 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. |
| Relapse occurrence in the CIS patients during 24 weeks of the trial | At each clinic visit or as the need arises. | 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. |
| 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). | At 24 weeks. | — |
Other
| Measure | Time frame | Description |
|---|---|---|
| serum 25(OH)D levels | 4 weekly over 24 weeks | a measure of response to oral dosing and adherence to therapy. |
| Serum calcium | Every 4 weeks for 24 weeks | a measure of calcium homeostasis |
| serum parathormone (iPTH) | 4 weekly over 24 weeks | a measure of parathyroid function |
| Number of participants with adverse events as a measure of safety and tolerability of vitamin D in doses of 5,000IU and 10,000IU daily | four weekly assessments over 24 weeks | — |
| serum urea | 4 weekly over 24 weeks | a measure of renal function |
| serum creatinine | 4 weekly over 24 weeks | a measure of renal function |
Countries
Ireland
Outcome results
None listed