Phase IIb Randomized, Double-Blind, Placebo-Controlled, Dose Ranging Trial to determine the safety and efficacy of Vitamin D3 in preventing the risk of MS in Patients with a first demyelinating event.
- Conditions
- Neurological - Multiple sclerosisClinically Isolated Syndrome - those who have experienced only one demyelinating event and are yet to receive a diagnosis of clinically definite Multiple Sclerosis (MS).
- Registration Number
- ACTRN12612001160820
- Lead Sponsor
- MS Research Australia
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Stopped early
- Sex
- All
- Target Recruitment
- 202
For inclusion in this study, a participant must meet the following criteria:
* aged between 18 and 65 years old inclusive
* have a first isolated, well-defined, uni- or multi-focal first demyelinating event (FDE)
* be able to receive first dose of study drug within 135 days of FDE symptom onset
* have an MRI brain scan that is supportive of demyelinating disease (Paty A or Paty B criteria) OR have at least one >5mm diameter T2/Flair brain lesion which must be in a periventricular, callosal, subcortical U-fibre or posterior fossa location AND must have at least one spinal cord lesion.
* an EDSS between 0 - 6.5 (inclusive)
* be able to give informed consent and sign the informed consent form
* be willing to avoid open-label vitamin D supplementation and external serum vitamin D testing for the duration of the study
* be willing to avoid use of sunbeds
* not have received any prior disease modifying treatment for MS other than glucocorticoids
* be willing to avoid treatment with beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, or other chemotherapy agent specifically for demyelinating disease until recurrent disease activity occurs (ie the primary endpoint is met)
* be able and willing to comply with all study procedures including MRI scanning as per protocol
* be willing to use effective contraceptive methods for the duration of the study and at least 6 months following.
Any of the following conditions will exclude a participant from the study:
* currently pregnant or breastfeeding
* documented or likely prior neurological event consistent with a diagnosis of clinically definite MS
* treatment with beta-interferon, glatiramer acetate, natalizumab, mitoxantrone, or other chemotherapy agent specifically for demyelinating disease
* a second clinical demyelinating event prior to randomisation
* a history of primary hyperparathyroidism or any other condition causing hypercalcaemia
* a history of sarcoidosis
* a history of renal calculi
* a history of treated osteoporosis or any other condition requiring treatment with calcium, vitamin D, bisposphonates, strontium ranelate, denosumab, raloxifene, calcitriol or teriparetide
* hypercalcaemia on screening blood tests
* an abnormal eGFR (<60 ml/min/1.73m2), or an elevated uric acid laboratory value (above normal range for the local laboratory used)
* concurrent diagnosis of other neurological, psychiatric or other disease which, in the opinion of the investigator, could impair capacity to provide informed consent, interfere with study compliance, or impair the participant’s ability to comply with the study protocol
* current enrolment in another interventional trial
* any contraindication to MRI scanning or intravenous Gadolinium including:
a) cardiac pacemaker
b) cardiac defibrillator
c) metal fragments in the eye
d) any other non-MRI compatible medical device/implant or medical condition
e) previous reaction to Gadolinium
f) severe claustrophobia.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method To determine the relative efficacy of oral, daily, Vitamin D3 (1,000IU or 5000IU or 10,000IU) compared with placebo, in reducing the risk of recurrent disease activity (clinical demyelinating event or MRI activity) in the 12 months following onset of a first demyelinating event.[12 months following onset of a first demyelinating event.]
- Secondary Outcome Measures
Name Time Method To assess whether a beneficial clinical and/or radiological response exists for oral Vitamin D supplementation in preventing MS in high-risk FDE participants[12 months post randomisation];To assess whether there is a dose response relationship between study medication and the study endpoints[12 months post registration];To assess whether there is a relationship between serum 25(OH)D level and study endpoints[12 months post randomization];To determine if oral Vitamin D3 therapy has an acceptable side effect and safety profile by monitoring the adverse events over the 12 months. Blood calcium will be monitored at each timepoint because there is the unlikely possibility that it may increase.[12 months post randomisation]