TerminatedPhase 2ACTRN12612001160820

Preventing the risk of Multiple Sclerosis using Vitamin D in patients with a first demyelinating event in Australia and New Zealand (PrevANZ)

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.

Sponsor

MS Research Australia

Enrollment

240 participants

Start Date

Jul 8, 2013

Study Type

Interventional

Conditions

Clinically Isolated Syndrome - those who have experienced only one demyelinating event and are yet to receive a diagnosis of clinically definite Multiple Sclerosis (MS).

Summary

There is a great deal of lay information to suggest that people with MS or at risk of MS should take oral Vitamin D supplementation. However, no adequately powered scientific study has examined the role of Vitamin D3 supplementation as prevention or treatment for MS. There is insufficient commercial interest in conducting such a study, but the need for evidence is great. If effective, oral Vitamin D supplementation could provide a low cost MS therapy with virtually no side effects. Sponsored by Multiple Sclerosis Research Australia, we therefore plan to conduct a randomised, placebo controlled, double-blind clinical trial to assess the efficacy of oral Vitamin D3 in preventing the development of Multiple Sclerosis in participants at high risk of MS (participants with a first demyelinating event, FDE). We will compare three doses of oral daily vitamin D3 (1,000IU 5,000IU or 10,000IU/day) to placebo. After agreeing to participate, participants will be randomly and blindly assigned to one of these four study arms and will continue to take study medication for 48 weeks. Scope: We plan to enrol 240 participants with FDE from 21 Australian and New Zealand MS trial centres over the course of three years. We may invite additional centres depending on recruitment and trial progress.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 65 Yearss

Inclusion Criteria13

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.

Exclusion Criteria20

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.

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Interventions

Vitamin D 1,000IU; 5,000IU; 10,000IU. Arm 1: Placebo once daily oral capsule for 48 weeks; Arm 2: Vitamin D 1,000IU once daily oral capsule for 48 weeks; Arm 3: Vitamin D 5,000IU once daily oral ca

Vitamin D 1,000IU; 5,000IU; 10,000IU. Arm 1: Placebo once daily oral capsule for 48 weeks; Arm 2: Vitamin D 1,000IU once daily oral capsule for 48 weeks; Arm 3: Vitamin D 5,000IU once daily oral capsule for 48 weeks and Arm 4: Vitamin D 10,000IU once daily oral capsule for 48 weeks.