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Title: Vitamin D did not reduce multiple sclerosis disease activity after a clinically isolated syndrome.
Austin Authors: Butzkueven, Helmut;Ponsonby, Anne-Louise;Stein, Mark S;Lucas, Robyn M;Mason, Deborah;Broadley, Simon;Kilpatrick, Trevor;Lechner-Scott, Jeannette;Barnett, Michael;Carroll, William;Mitchell, Peter;Hardy, Todd A;Macdonell, Richard A L ;McCombe, Pamela;Lee, Andrew;Kalincik, Tomas;van der Walt, Anneke;Lynch, Chris;Abernethy, David;Willoughby, Ernest;Barkhof, Frederik;MacManus, David;Clarke, Michael;Andrew, Julie;Morahan, Julia;Zhu, Chao;Dear, Keith;Taylor, Bruce V
Affiliation: Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
The Florey Institute of Neuroscience and Mental Health
Department of Diabetes and Endocrinology, The Royal Melbourne Hospital, Parkville, VIC 3010, Australia.
Australian National University, Canberra, ACT 0200, Australia.
Department of Neurology, Christchurch Hospital, Christchurch 8011, New Zealand.
School of Medicine and Dentistry, Griffith University, Southport, QLD 4222, Australia.
Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, VIC 3010, Australia.
Department of Neurology, John Hunter Hospital, Newcastle, NSW 2305, Australia.
Brain and Mind Research Institute University of Sydney, Sydney, NSW 2050, Australia.
Department of Neurology, Sir Charles Gairdner Hospital and Centre for Neuromuscular and Neurological Disorders and Perron Institute, University of Western Australia, WA 6009, Australia.
Department of Radiology, Royal Melbourne Hospital, Melbourne, VIC 3010, Australia.
Concord Hospital, University of Sydney, Sydney NSW 2139, Australia.
University of Queensland, Centre for Clinical Research, Brisbane, QLD 4029, Australia.
Flinders University College of Medicine and Public Health, Adelaide, SA 5042, Australia.
Neuroimmunology Centre, Department of Neurology, Royal Melbourne Hospital; CORe, Department of Medicine, University of Melbourne, Melbourne, VIC 3010, Australia.
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
Midland Neurology, Hamilton 3240, Waikato, New Zealand.
Department of Neurology, Wellington Hospital, Wellington 6021, New Zealand.
Department of Neurology, Auckland Hospital, Auckland 1023, New Zealand.
Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands.;Queen Square Institute of Neurology and Centre for Medical Image Computing, University College London, WC1N 3BG, UK.
University College London Queen Square Institute of Neurology, Queen Square MS Centre, London, WC1N 3BG, UK.
School of Biomedical Sciences, University of Western Australia, Perth, WA 6009, Australia.
Neurosciences Trials Australia, North Melbourne, VIC 3051, Australia.
Multiple Sclerosis Australia, North Sydney, NSW 2059, Australia.
Department of Neuroscience, Central Clinical School, Monash University, Melbourne, VIC 3004, Australia.
School of Public Health, University of Adelaide, SA 5005, Australia.
Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania 7000, Australia.
Issue Date: 12-Dec-2023
Date: 2023
Publication information: Brain : A Journal of Neurology 2023-12-12
Abstract: Low serum levels of 25-hydroxyvitamin D (25(OH)D), and low sunlight exposure, are known risk factors for the development of multiple sclerosis. Add-on vitamin D supplementation trials in established multiple sclerosis have been inconclusive. The effects of vitamin D supplementation to prevent multiple sclerosis is unknown. We aimed to test the hypothesis that oral vitamin D3 supplementation in high-risk clinically isolated syndrome (abnormal MRI, at least three T2 brain and/or spinal cord lesions), delays time to conversion to definite multiple sclerosis, that the therapeutic effect is dose-dependent, and that all doses are safe and well tolerated. We conducted a double-blind trial in Australia and New Zealand. Eligible participants were randomised 1:1:1:1 to placebo, 1000, 5000, or 10 000 IU of oral vitamin D3 daily within each study centre (n=23) and followed for up to 48 weeks. Between 2013 and 2021, we enrolled 204 participants. Brain MRI scans were performed at baseline, 24 and 48 weeks. The main study outcome was conversion to clinically definite multiple sclerosis based on the 2010 McDonald criteria defined as either a clinical relapse or new brain MRI T2 lesion development. We included 199 cases in the intention-to-treat analysis based on assigned dose. Of these, 116 converted to multiple sclerosis by 48 weeks (58%). Compared to placebo, the HRs (95%CI) for conversion were 1000 IU 0.87 (0.50, 1.50); 5000 IU 1.37 (0.82, 2.29); and 10 000 IU 1.28 (0.76, 2.14). In an adjusted model including age, sex, latitude, study centre, and baseline symptom number, clinically isolated syndrome onset site, presence of infratentorial lesions, and use of steroids, the HRs (versus placebo) were 1000 IU 0.80 (0.45, 1.44); 5000 IU 1.36 (0.78, 2.38); 10 000 IU 1.07 (0.62, 1.85). Vitamin D3 supplementation was safe and well tolerated. We did not demonstrate reduction in multiple sclerosis disease activity by vitamin D3 supplementation after a high-risk clinically isolated syndrome. Trial registration Australian Clinical Trials Registration Number ACTRN12612001160820.
DOI: 10.1093/brain/awad409
ORCID: 0000-0002-6581-3657
Journal: Brain : A Journal of Neurology
PubMed URL: 38085047
ISSN: 1460-2156
Type: Journal Article
Subjects: clinical trial
multiple sclerosis
vitamin D
Appears in Collections:Journal articles

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