RT Journal Article
SR Electronic
T1 Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study
JF Journal of Neurology, Neurosurgery & Psychiatry
JO J Neurol Neurosurg Psychiatry
FD BMJ Publishing Group Ltd
SP jnnp-2018-319294
DO 10.1136/jnnp-2018-319294
A1 Ryuji Kaji
A1 Takashi Imai
A1 Yasuo Iwasaki
A1 Koichi Okamoto
A1 Masanori Nakagawa
A1 Yasuo Ohashi
A1 Takao Takase
A1 Takahisa Hanada
A1 Hiroki Shimizu
A1 Kunio Tashiro
A1 Shigeki Kuzuhara
YR 2019
UL http://jnnp.bmj.com/content/early/2019/01/12/jnnp-2018-319294.abstract
AB Objective To evaluate the efficacy and safety of intramuscular ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis (ALS).Methods 373 patients with ALS (El Escorial definite or probable; laboratory-supported probable; duration ≤36 months) were randomly assigned to placebo, 25 mg or 50 mg of methylcobalamin groups. The primary endpoints were the time interval to primary events (death or full ventilation support) and changes in the Revised ALS Functional Rating Scale (ALSFRS-R) score from baseline to week 182. Efficacy was also evaluated using post-hoc analyses in patients diagnosed early (entered ≤12 months after symptom onset).Results No significant differences were detected in either primary endpoint (minimal p value=0.087). However, post-hoc analyses of methylcobalamin-treated patients diagnosed and entered early (≤12 months’ duration) showed longer time intervals to the primary event (p<0.025) and less decreases in the ALSFRS-R score (p<0.025) than the placebo group. The incidence of treatment-related adverse events was similar and low in all groups.Conclusion Although ultra-high-dose methylcobalamin did not show significant efficacy in the whole cohort, this treatment may prolong survival and retard symptomatic progression without major side effects if started early.Trial registration number NCT00444613.