A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis

M S Stein, Y Liu, Orla M Gray, J E Baker, Scott C Kolbe, Michael R Ditchfield, Gary F Egan, Peter J Mitchell, Leonard C Harrison, Helmut Butzkueven, Trevor J Kilpatrick

Research output: Contribution to journalArticleResearchpeer-review

Abstract

OBJECTIVE: Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated the effects of high-dose vitamin D2 (D2) in MS. METHODS: Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130-175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses. RESULTS: Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04). CONCLUSION: We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.
Original languageEnglish
Pages (from-to)1611 - 1618
Number of pages8
JournalNeurology
Volume77
Issue number17
DOIs
Publication statusPublished - 2011

Cite this

Stein, M S ; Liu, Y ; Gray, Orla M ; Baker, J E ; Kolbe, Scott C ; Ditchfield, Michael R ; Egan, Gary F ; Mitchell, Peter J ; Harrison, Leonard C ; Butzkueven, Helmut ; Kilpatrick, Trevor J. / A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. In: Neurology. 2011 ; Vol. 77, No. 17. pp. 1611 - 1618.
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title = "A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis",
abstract = "OBJECTIVE: Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated the effects of high-dose vitamin D2 (D2) in MS. METHODS: Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130-175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses. RESULTS: Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04). CONCLUSION: We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.",
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Stein, MS, Liu, Y, Gray, OM, Baker, JE, Kolbe, SC, Ditchfield, MR, Egan, GF, Mitchell, PJ, Harrison, LC, Butzkueven, H & Kilpatrick, TJ 2011, 'A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis' Neurology, vol. 77, no. 17, pp. 1611 - 1618. https://doi.org/10.1212/WNL.0b013e3182343274

A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis. / Stein, M S; Liu, Y; Gray, Orla M; Baker, J E; Kolbe, Scott C; Ditchfield, Michael R; Egan, Gary F; Mitchell, Peter J; Harrison, Leonard C; Butzkueven, Helmut; Kilpatrick, Trevor J.

In: Neurology, Vol. 77, No. 17, 2011, p. 1611 - 1618.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - A randomized trial of high-dose vitamin D2 in relapsing-remitting multiple sclerosis

AU - Stein, M S

AU - Liu, Y

AU - Gray, Orla M

AU - Baker, J E

AU - Kolbe, Scott C

AU - Ditchfield, Michael R

AU - Egan, Gary F

AU - Mitchell, Peter J

AU - Harrison, Leonard C

AU - Butzkueven, Helmut

AU - Kilpatrick, Trevor J

PY - 2011

Y1 - 2011

N2 - OBJECTIVE: Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated the effects of high-dose vitamin D2 (D2) in MS. METHODS: Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130-175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses. RESULTS: Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04). CONCLUSION: We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.

AB - OBJECTIVE: Higher latitude, lower ultraviolet exposure, and lower serum 25-hydroxyvitamin D (25OHD) correlate with higher multiple sclerosis (MS) prevalence, relapse rate, and mortality. We therefore evaluated the effects of high-dose vitamin D2 (D2) in MS. METHODS: Adults with clinically active relapsing-remitting MS (RRMS) were randomized to 6 months double-blind placebo-controlled high-dose vitamin D2, 6,000 IU capsules, dose adjusted empirically aiming for a serum 25OHD 130-175 nM. All received daily low-dose (1,000 IU) D2 to prevent deficiency. Brain MRIs were performed at baseline, 4, 5, and 6 months. Primary endpoints were the cumulative number of new gadolinium-enhancing lesions and change in the total volume of T2 lesions. Secondary endpoints were Expanded Disability Status Scale (EDSS) score and relapses. RESULTS: Twenty-three people were randomized, of whom 19 were on established interferon or glatiramer acetate (Copaxone) treatment. Median 25OHD rose from 54 to 69 nM (low-dose D2) vs 59 to 120 nM (high-dose D2) (p = 0.002). No significant treatment differences were detected in the primary MRI endpoints. Exit EDSS, after adjustment for entry EDSS, was higher following high-dose D2 than following low-dose D2 (p = 0.05). There were 4 relapses with high-dose D2 vs none with low-dose D2 (p = 0.04). CONCLUSION: We did not find a therapeutic advantage in RRMS for high-dose D2 over low-dose D2 supplementation. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that high-dose vitamin D2 (targeting 25OHD 130-175 nM), compared to low-dose supplementation (1,000 IU/d), was not effective in reducing MRI lesions in patients with RRMS.

UR - http://www.ncbi.nlm.nih.gov/pubmed/22025459

U2 - 10.1212/WNL.0b013e3182343274

DO - 10.1212/WNL.0b013e3182343274

M3 - Article

VL - 77

SP - 1611

EP - 1618

JO - Neurology

JF - Neurology

SN - 0028-3878

IS - 17

ER -