Amyotrophic Lateral SclerosisPhase 3JETALSNCT03548311
Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
A Phase 3 study testing methylcobalamin and saline solution in people with Amyotrophic Lateral Sclerosis, run by Eisai Co., Ltd. at 16 sites in Japan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 years and older
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- methylcobalamin and saline solution
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 130 participants
- Where
- 16 sitesJapan
- Study dates
- 1 Nov 2017to 18 Feb 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Treatment and OLE Phase:
- ALS patients within 12 months after clinical onset at the entry
- Diagnosed based on updated Awaji 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
- Tsunagi Phase:
- The subjects for the Tsunagi phase are patients with ALS who are continuing the administration of this drug at the time of approval, and have obtained consent for the transition to the Tsunagi phase.
Who cannot join
- Treatment and OLE Phase:
- 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
Show all 16Show fewer
- 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
- Tsunagi Phase:
- Not applicable.
Trial locations and contacts
16 sites in 1 country.
16 sites in 1 country
Japan16 sites
Chiba University Hospital
Chiba, 260-8677
Murakami Karindo Hospital
Fukuoka, 819-8585
Ioh National Hospital
Kanazawa, Ishikawa-ken, 920-0192
Kobe Central Munincipal Medical center
Kobe, Hyōgo, 650-0047
Miyoshi Neurological Clinic
Miyoshi, Hiroshima, 728-0013
Nagoya University Hospital
Nagoya, Aichi-ken, 466-8560
Okayama University Hospital
Okayama, 770-8558
Shiga Medical University Hospital
Ōtsu, Shiga, 520-2192
Kitasato University East Hospital
Sagamihara, Kanagawa, 252-0380
Sapporo Medical University Hospital
Sapporo, Hokkaido, 060-8543
Tokushima University Hospital
Tokushima, 770-8503
Juntendo University Hospital
Tokyo, 113-8431
Toho University Hospital
Tokyo, 143-8541
Teikyo University Hospital
Tokyo, 173-8606
Tokyo Metropolitan Neurological Hospital
Tokyo, 183-0042
Wakayama Medical University Hospital
Wakayama, 641-8509
About this study
Official title: Japanese Early-stage Clinical Trial of Ultra-high Dose Methylcobalamin for Amyotrophic Lateral Sclerosis: a Pivotal Phase 3 Randomized Controlled Study
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.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- methylcobalamin, saline solution
- Keywords
- ALS, motor neuron disease, Lou Gehrig's disease
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Motor Neuron Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
methylcobalaminDrug
Patients receive methylcobalamin 50mg intramuscular injection twice a week.
saline solutionDrug
Patients receive saline solution intramuscular injection twice a week.
| Study group | Role | What they receive |
|---|---|---|
| Treatment Phase: Placebo | Placebo comparator | intramuscular injection of saline solution Receives: Drug: saline solution |
| Treatment Phase: methylcobalamin | Active comparator | intramuscular injection of methylcobalamin Receives: Drug: methylcobalamin |
| OLE Phase: methylcobalamin | Experimental | intramuscular injection of methylcobalamin Receives: Drug: methylcobalamin |
| Tsunagi Phase: methylcobalamin | Experimental | intramuscular injection of methylcobalamin Receives: Drug: methylcobalamin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Treatment Phase: ALSFRS-R
Drop of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (maximum or normal 48 and minimum 0; higher values represent better condition)
Measured: during 16 weeks of test period
Secondary outcomes (7)
Treatment Phase: time to event
time from the randomization to the onset of any of the event (24-hour use of noninvasive respiratory support, use of invasive respiratory support, or death)
Measured: during 16 weeks of test period
Treatment Phase: %Functional Vital Capacity (FVC)
changes of per cent Functional Vital Capacity
Measured: during 16 weeks of test period
Treatment Phase: homocystein
changes of serum levels of homocystein
Measured: during 16 weeks of test period
Treatment Phase: Manual Muscle Testing (MMT)
changes of sum of Medical Research Council scales of manual muscle testing, ranging 5 (normal), 4, 4+, 3, 2, 1, 0 (minimal) ( for analysis each is converted to 6, 5, 4, 3, 2, 1, 0) of the 11 muscles in the limbs (5x2) and neck(1)
Measured: during 16 weeks of test period
Treatment Phase: Norris scale
changes of Norris scale (39 normal - 0 worst)
Measured: during 16 weeks of test period
Treatment Phase: Grip Power
changes of sum of grip power in kilograms on both sides
Measured: during 16 weeks of test period
Treatment Phase: 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40)
changes of sum of ALSAQ-40 (40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire) score (40 normal - 200 worst)
Measured: during 16 weeks of test period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2018
- Study start1 Nov 2017
- Primary completion14 Feb 2020
- Study completion18 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- double-blinded randomized controlled
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 130 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eisai Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- University of Tokushima
- Responsible party
- Sponsor
- Investigators
- Ryuji Kaji, MD, Study director, Tokushima University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03548311
- Sponsor's protocol ID
- 763
- Acronym
- JETALS
- Status last verified
- Feb 2025
- First submitted
- 14 May 2018
- Last updated
- 26 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: anonymous data are available
Publications
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.
PubMed 25982504Kaji 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.
PubMed 9843082Oki 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.
PubMed 35532908Oki 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.
PubMed 30578206
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Japanese Early-stage Clinical Trial of Ultra-high Dose Methylcobalamin for Amyotrophic Lateral Sclerosis: a Pivotal Phase 3 Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT03548311
- Acronym / sponsor ID
- JETALS / 763
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- ALS, motor neuron disease, Lou Gehrig's disease
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 130 participants (actual)
- Lead sponsor
- Eisai Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- University of Tokushima
- Study start
- 1 Nov 2017 (actual)
- Primary completion
- 14 Feb 2020 (actual)
- Study completion
- 18 Feb 2025 (actual)
- First posted
- 7 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- double-blinded randomized controlled
| Arm | Type | Receives |
|---|---|---|
| Treatment Phase: Placebo | Placebo comparator | Drug: saline solutionintramuscular injection of saline solution |
| Treatment Phase: methylcobalamin | Active comparator | Drug: methylcobalaminintramuscular injection of methylcobalamin |
| OLE Phase: methylcobalamin | Experimental | Drug: methylcobalaminintramuscular injection of methylcobalamin |
| Tsunagi Phase: methylcobalamin | Experimental | Drug: methylcobalaminintramuscular injection of methylcobalamin |
Who may qualify
- Ages
- 20 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- ALS patients within 12 months after clinical onset at the entry
- Diagnosed based on updated Awaji 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| methylcobalaminPatients receive methylcobalamin 50mg intramuscular injection twice a week. | Drug | OLE Phase: methylcobalamin, Treatment Phase: methylcobalamin, Tsunagi Phase: methylcobalamin |
| saline solutionPatients receive saline solution intramuscular injection twice a week. | Drug | Treatment Phase: Placebo |
Primary outcome
Treatment Phase: ALSFRS-R
Time frame: during 16 weeks of test period
Drop of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (maximum or normal 48 and minimum 0; higher values represent better condition)
7 secondary outcomes
Treatment Phase: time to event
Time frame: during 16 weeks of test period
Treatment Phase: %Functional Vital Capacity (FVC)
Time frame: during 16 weeks of test period
Treatment Phase: homocystein
Time frame: during 16 weeks of test period
Treatment Phase: Manual Muscle Testing (MMT)
Time frame: during 16 weeks of test period
Treatment Phase: Norris scale
Time frame: during 16 weeks of test period
Treatment Phase: Grip Power
Time frame: during 16 weeks of test period
Treatment Phase: 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40)
Time frame: during 16 weeks of test period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2025.
- Results publication: PubMed 25982504Ikeda 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 publication: PubMed 9843082Kaji 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.
- Derived from this study: PubMed 35532908Oki 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.
- Derived from this study: PubMed 30578206Oki 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.
- Individual participant dataSharing planned: Yes. anonymous data are available
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ryuji Kaji, MD study director
Tokushima University Hospital
16 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing methylcobalamin and saline solution in people with Amyotrophic Lateral Sclerosis, run by Eisai Co., Ltd. at 16 sites in Japan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 16 sites in Japan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Treatment Phase: ALSFRS-R (time frame: during 16 weeks of test period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03548311, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2025; AzTrials last refreshed its copy on 8 Nov 2026.