VITAMIN D MS PREVENTION TRIAL (PrevANZ)

The Vitamin D MS Prevention Trial – PrevANZ is a world-first clinical trial being undertaken as a collaboration between New Zealand and Australian researchers that will test whether vitamin D supplementation can prevent MS in those at risk of developing the disease.

This is a Phase IIb randomised, double blind, placebo-controlled trial testing a range of doses of oral vitamin D supplements in people with a first episode of symptoms that may be a precursor to MS (known as clinically isolated syndrome or CIS). This might include symptoms such as blurred vision (optic neuritis) or limb weakness (transverse myelitis) (these symptoms may also be described as a first demyelinating event).

The trial will test whether vitamin D supplements can delay or prevent a second episode, or attack, which would lead to a diagnosis of MS. It also tests the appropriate dosage levels and safety.

The need for the vitamin D MS prevention trial has arisen from a now significant body of evidence for the role that vitamin D deficiency plays in MS. However, to date there has not been a clinical trial conducted to provide the necessary evidence on the benefits that can be expected from vitamin D supplementation or the correct dose.

MS Research Australia and our colleagues in the MS research community see this trial as a high priority and an area in which the expertise in Australia and New Zealand can contribute significantly to the prevention and better treatment of MS globally.

The Steering Committee

A team of clinicians and researchers from Australia and New Zealand, with expertise in MS neurology, MS clinical trials, endocrinology and epidemiology has been assembled to oversee the trial. The trial is coordinated and funded by MS Research Australia. This has been made possible by generous support from the Australian state MS organisations, particularly, WA, Queensland and Tasmania, as well as Foundation 5 Million+, the Trish MS Research Foundation, and the John T Reid Trust.

Together with the Steering Committee, chaired by Professor Bill Carroll from the Sir Charles Gairdner Hospital, Perth, a collaborative team of neurologists, led by Professor Helmut Butzkueven from the University of Melbourne, and Professor Bruce Taylor, Menzies Institute for Medical Research, Hobart, will undertake this study across 18 sites in Australia and New Zealand.

The Timeline

The vitamin D MS Prevention Trial commenced recruitment in June 2013. The trial aims to enrol 240 people with CIS. It is expected the trial will be complete in 2019. The trial will test 3 dosage levels of daily oral vitamin D3 supplements (1000, 5000 & 10,000 International Units) against placebo (dummy tablets) .

The role of vitamin D in MS

The evidence for the role of vitamin D deficiency in MS is now very strong and was reinforced by the internationally important Australian study (Ausimmune, 2004-2007), comparing MS patients in with CIS in Brisbane, Newcastle, Geelong and Hobart. Vitamin D deficiency is thought to play a role in MS since geographical areas of lower levels of UV radiation, and hence lower vitamin D synthesis in the skin, have higher incidences of MS. Variations in genes involved in the vitamin D metabolism pathway have been implicated in susceptibility to MS and vitamin D deficiency has also been shown to be associated with a higher rate of relapses in people with established MS.

Taking part in the PrevANZ trial

People with CIS who are interested in taking part should discuss participation with their neurologist. Full details of the trial, including eligibility criteria for participants can be found here.

Inclusion criteria

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 120 days of FDE symptom onset
• have an MRI brain scan that is supportive of demyelinating disease (Paty A or Paty B criteria) 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.

Please note people who have already been diagnosed with MS are not eligible to participate in the trial.

People with MS who are concerned about their vitamin D levels should seek advice from their GP or neurologist.

Participating in New Zealand

There are 5 participating sites in New Zealand:

Auckland Hospital
Investigator – Dr Ernie Willoughby
Coordinator – Roddi Laurence
Email – RoddiL@adhb.govt.co.nz
Phone – 09 307 4949 Ext 25816

Christchurch Hospital
Investigator – Dr Deborah Mason
Coordinator – Jane Eagle
Email – jane.eagle@cdhb.health.nz
Phone – 03 378 6130

Dunedin Hospital
Investigator – Dr John Mottershead
Coordinator – Sharon Stevenson-Hall
Email – Sharon.Stevenson-Hall@southerndhb.govt.nz
Phone – 03 470 0999

Waikato Hospital
Investigator – Dr Chris Lynch
Coordinator – Linda Gilbertson
Email – Linda.Gilbertson@waikatodhb.health.nz
Phone – 02 154 9778

Wellington Hospital
Investigator – Dr David Abernethy
Coordinator – Liz Goode
Email – liz.goode@ccdhb.org.nz
Phone – 04 806 0078

See MS Research Australia for more information and details about Australian sites