Evidence map›Paper›PMID 30636701›Full record

Trial reportJournal of neurology, neurosurgery, and psychiatry2019

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

Ryuji Kaji, Takashi Imai, Yasuo Iwasaki, Koichi Okamoto, Masanori Nakagawa, Yasuo Ohashi, Takao Takase, Takahisa Hanada, Hiroki Shimizu, Kunio Tashiro and 1 more

Registry-linked trialOpen access · hybridAbstract readClinical Trial, Phase IIClinical Trial, Phase IIIRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Journal of neurology, neurosurgery, and psychiatry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00444613 (A Phase II/III Study in Patients With Amyotrophic Lateral Sclerosis), which is not on this map. Cited by 41 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed, 2 pooled it
6.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT00444613 phase2 / phase3completednot on this map

A Phase II/III Study in Patients With Amyotrophic Lateral Sclerosis (ALS)

TypeinterventionalSponsorEisai Co., Ltd.Ran2007 to 2014Enrolled373ConditionsAmyotrophic Lateral Sclerosis (ALS)ArmsE0302 (mecobalamin), Placebo
3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 2 syntheses or guidelines pooled it, 77 citations in OpenAlex.

  1. The level of homocysteine in amyotrophic lateral sclerosis: a systematic review and meta-analysis.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2023
    Pooled it
  2. Pooled it
  3. Trial
  4. Trial
  5. Review
  6. Article
  7. Review
  8. Red urine in a 68-year-old man with amyotrophic lateral sclerosis.Journal of general and family medicine · 2025
    Article
  9. Article
  10. Review
  11. Article
  12. Review
  13. Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Microbiome and micronutrient in ALS: From novel mechanisms to new treatments.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2024
    Review
  19. Review
  20. Therapeutic targeting of ALS pathways: Refocusing an incomplete picture.Annals of clinical and translational neurology · 2023
    Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

11 authors at 8 institutions in 1 country.

Ryuji KajiDepartment of Neurology, Tokushima University Hospital, Tokushima, Japan rkaji@tokushima-u.ac.jp.
Takashi ImaiNational Hospital Organization Miyagi National Hospital, Sendai, Japan.
Yasuo IwasakiDepartment of Neurology, Toho University Omori Medical Center, Tokyo, Japan.
Koichi OkamotoDepartment of Neurology, Geriatrics Research Institute and Hospital, Maebashi, Gunma, Japan.
Masanori NakagawaNorth Medical Center, Kyoto Prefectural University of Medicine, Kyoto, Japan.
Yasuo OhashiDepartment of Integrated Science and Engineering for Sustainable Society, Chuo University, Hachioji, Japan.
Takao TakaseEisai, Tokyo, Japan.
Takahisa HanadaEisai, Tokyo, Japan.
Hiroki ShimizuEisai, Tokyo, Japan.
Kunio TashiroDepartment of Neurology, Hokuyukai Neurological Hospital, Sapporo, Japan.
Shigeki KuzuharaSchool of Nursing, Suzuka University of Medical Science, Suzuka, Japan.
Eisai (Japan) · JPChuo University · JPFukuoka Tokushukai Hospital · JPHokuyukai Neurology Hospital · JPKyoto Prefectural University of Medicine · JPSuzuka University of Medical Science · JPToho University Omori Medical Center · JPTokushima University Hospital · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

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 NUMBER: NCT00444613.

Indexed as

AgedAmyotrophic Lateral SclerosisDouble-Blind MethodFemaleHumansInjections, IntramuscularMaleMiddle AgedRespiration, ArtificialSurvival RateVitamin B 12mecobalaminVitamin B 12

Identifiers

PMID30636701
PMCPMC6581107
OpenAlexW2909006243

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.