Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
Summary
To examine the clinical efficacy and safety of ultra-high dose (50mg, im, twice a week) methylcobalamin in retarding the progression of symptoms in amyotrophic lateral sclerosis (ALS) patients, we enroll ALS patients diagnosed by Updated Awaji Criteria within 12 months after the clinical onset. First they are followed for 12 weeks with Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) scores, and only those who exhibit drops of 1-2 points are allowed to enter into the test period. A total of 128 patients are randomized and the half having placebo. They are blindly evaluated for drops of ALSFRS-R in 16 weeks, as the primary outcome. After this, all subjects receive methylcobalamin.
Timeline
- Start
- 2017-11-01
- Primary completion
- 2020-02-14
- Completion
- 2025-02-18
Outcome
Met primary endpoint
paper The least square means difference in ALSFRS-R total score at week 16 of the randomized period was 1.97 points greater with methylcobalamin than placebo PMID 35532908 ↗
paper (-2.66 vs -4.63; 95% CI, 0.44-3.50; P = .01). PMID 35532908 ↗
release “In JETALS, the mecobalamin 50mg group showed a statistically significant slowing of progression compared to the placebo group” eisai.com ↗
Publications
- Results Ikeda K, Iwasaki Y, Kaji R. Neuroprotective effect of ultra-high dose methylcobalamin in wobbler mouse model of amyotrophic lateral sclerosis. J Neurol Sci. 2015 Jul 15;354(1-2):70-4. doi: 10.1016/j.jns.2015.04.052. Epub 2015 May 8.
- Results Kaji R, Kodama M, Imamura A, Hashida T, Kohara N, Ishizu M, Inui K, Kimura J. Effect of ultrahigh-dose methylcobalamin on compound muscle action potentials in amyotrophic lateral sclerosis: a double-blind controlled study. Muscle Nerve. 1998 Dec;21(12):1775-8. doi: 10.1002/(sici)1097-4598(199812)21:123.0.co;2-v.
- Oki R, Izumi Y, Fujita K, Miyamoto R, Nodera H, Sato Y, Sakaguchi S, Nokihara H, Kanai K, Tsunemi T, Hattori N, Hatanaka Y, Sonoo M, Atsuta N, Sobue G, Shimizu T, Shibuya K, Ikeda K, Kano O, Nishinaka K, Kojima Y, Oda M, Komai K, Kikuchi H, Kohara N, Urushitani M, Nakayama Y, Ito H, Nagai M, Nishiyama K, Kuzume D, Shimohama S, Shimohata T, Abe K, Ishihara T, Onodera O, Isose S, Araki N, Morita M, Noda K, Toda T, Maruyama H, Furuya H, Teramukai S, Kagimura T, Noma K, Yanagawa H, Kuwabara S, Kaji R; Japan Early-Stage Trial of Ultrahigh-Dose Methylcobalamin for ALS (JETALS) Collaborators. Efficacy and Safety of Ultrahigh-Dose Methylcobalamin in Early-Stage Amyotrophic Lateral Sclerosis: A Randomized Clinical Trial. JAMA Neurol. 2022 Jun 1;79(6):575-583. doi: 10.1001/jamaneurol.2022.0901.
- Oki R, Izumi Y, Nodera H, Sato Y, Nokihara H, Kanai K, Sonoo M, Urushitani M, Nishinaka K, Atsuta N, Kohara N, Shimizu T, Kikuchi H, Oda M, Ikeda K, Nagai M, Komai K, Kojima Y, Kuzume D, Isose S, Shimohama S, Abe K, Ito H, Noda K, Ishihara T, Morita M, Shimohata T, Teramukai S, Kagimura T, Noma K, Yanagawa H, Kuwabara S, Kaji R; JETALS. The Japanese Early-Stage Trial of High-Dose Methylcobalamin for Amyotrophic Lateral Sclerosis (JETALS): Protocol for a Randomized Controlled Trial. JMIR Res Protoc. 2018 Dec 21;7(12):e12046. doi: 10.2196/12046.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | methylcobalamin | Small molecule | 50 mg | Intramuscular |