Japanese Early-stage Clinical Trial of Ultra-high Dose Methylcobalamin for Amyotrophic Lateral Sclerosis: a Pivotal Phase 3 Randomized Controlled Study

Study Purpose:

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 revised-Awaji-El Escorial 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.

Study Status:

Not recruiting


Amyotrophic Lateral Sclerosis

Study Type:


Type of Intervention:


Intervention Name:

methylcobalamin, saline solution




Phase 3

Study Chair(s)/Principal Investigator(s):

Ryuji Kaji, MD, Tokushima University Hospital

Clinicaltrials.gov ID:


Neals Affiliated?


Coordinating Center Contact Information

Yuisin Izumi, MD / email hidden; JavaScript is required / 81-88-633-7207

Study Sponsor:

University of Tokushima

Estimated Enrollment:


Estimated Study Start Date:

11 / 01 / 2017

Estimated Study Completion Date:

03 / 31 / 2020

Posting Last Modified Date:

06 / 26 / 2018

Date Study Added to neals.org:

06 / 07 / 2018

Minimum Age:

20 Years

Maximum Age:


Inclusion Criteria:

- ALS patients within 12 months after clinical onset at the entry

- Updated Awaji combined with El Escorial criteria: definite, probably or laboratory supported probable

- Decline of ALSFRSR being 1 or 2 during observation period of 12 weeks

- Japanese Clinical Severity Scale 1 or 2

- Those who can visit the participating medical centers

Exclusion Criteria:

- Those who have tracheostomy

- Those who had NIPPV

- %FVC<60%

- Those who have Chronic Obstructive Pulmonary Disease (COPD)

- Those who have symptoms and signs of B12 deficiency

- Those who had edaravone less than 4 weeks prior to entry

- Those who changed the schedule and dosing of riluzole

- Those who have dementia

- Those who have the possibility of pregnancy

- Those who have serious respiratory or cardiac diseases

- Those who have malignancies

- Those who participated other clinical trials within 12 weeks

- Those who have allergies to B12 and related compounds

Nagoya University Hospital | Recruiting

Naoki Atsuta, MD / 81-52-741-2111

Nagoya, Aichi 466-8560

Miyoshi Neurological Clinic | Recruiting

Masaya Oda, MD

Miyoshi, Hiroshima 728-0013

Sapporo Medical University Hospital | Recruiting

Shun Shimohama, MD / 81-11-611-2111

Sapporo, Hokkaido 060-8543

Kobe Central Munincipal Medical center | Recruiting

Nobuo Kohara, MD / 81-78-302-4321

Kobe, Hyogo 650-0047

Ioh National Hospital | Recruiting

Kiyonobu Komai, MD / 81-76-258-1180

Kanazawa, Ishikawa 920-0192

Kitasato University East Hospital | Recruiting

Makiko Nagai, MD / 81-42-748-9111

Sagamihara, Kanagawa 252-0380

Shiga Medical University Hospital | Recruiting

Makoto Urushidani, MD / 81-77-548-2111

Otsu, Shiga 520-2192

Chiba University Hospital | Recruiting

Satoshi Kuwabara, MD / 81-43-222-7171 / email hidden; JavaScript is required

Chiba 260-8677

Murakami Karindo Hospital | Recruiting

Hitoshi Kikuchi, MD / 81-92-811-3331

Fukuoka 819-8585

Okayama University Hospital | Recruiting

Koji Abe, MD / 88-86-223-7151 / email hidden; JavaScript is required

Okayama 770-8558

Tokushima University Hospital | Recruiting

Hiroyuki Nodera, MD / 81-88-633-9658 / email hidden; JavaScript is required

Tokushima 770-8503

Juntendo University Hospital | Recruiting

Kazuaki Kanai, MD

Tokyo 113-8431

Toho University Hospital | Recruiting

Tokyo 143-8541

Teikyo University Hospital | Recruiting

Masahiro Sonoo, MD

Tokyo 173-8606

Tokyo Metropolitan Neurological Hospital | Recruiting

Tokyo 183-0042

Wakayama Medical University Hospital | Recruiting

Hidefumi Ito, MD / 81-73-447-2300

Wakayama 641-8509