Ultra-high-dose methylcobalamin in amyotrophic lateral sclerosis: a long-term phase II/III randomised controlled study

Abstract

ObjectiveTo evaluate the efficacy and safety of intramuscular ultra-high-dose methylcobalamin in patients with amyotrophic lateral sclerosis (ALS).Methods373 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).ResultsNo 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.ConclusionAlthough 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 numberNCT00444613.

Duality of P2X7 Receptor in Amyotrophic Lateral Sclerosis

“…- Methylcobalamin is a vitamin B12 analog that enhances the survival of ALS motor neurons in vitro ( Ito et al., 2017 ) and may prolong survival and delay disease progression in patients, if started early ( Kaji et al., 2019 ).…”

Critical design considerations for time-to-event endpoints in amyotrophic lateral sclerosis clinical trials

“…However, early-enrolled participants would remain in the trial for a considerable amount of time, which may increase dropout rates. The feasibility of a prolonged follow-up period in ALS has been shown before by the Ceftriaxone trial,29 and recently by a trial with methylcobalamin,36 where some patients participated for over 4 years. Registry data from large longitudinal population-based cohorts could additionally provide insight into follow-up patterns, as patients are often monitored from diagnosis until death.…”

Quality of life and muscle strength improvement in an amyotrophic lateral sclerosis patient after nutraceuticals

“…Moreover, multivariate logistic regression revealed a robust direct association between plasma homocysteine levels and ALS presence and a shorter interval onset ALS diagnosis [16]. A high dose of methylcobalamin, a methylating agent, was tested in ALS, showing a prolonged survival and retarding symptomatic progression without significant side effects if started early in these patients [17].…”