NCT03548311

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
130

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Nov 2017

Longer than P75 for phase_3

Geographic Reach
1 country

16 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

November 1, 2017

Completed
6 months until next milestone

First Submitted

Initial submission to the registry

May 14, 2018

Completed
24 days until next milestone

First Posted

Study publicly available on registry

June 7, 2018

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 14, 2020

Completed
5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

February 18, 2025

Completed
Last Updated

March 26, 2025

Status Verified

February 1, 2025

Enrollment Period

2.3 years

First QC Date

May 14, 2018

Last Update Submit

March 25, 2025

Conditions

Amyotrophic Lateral Sclerosis

Keywords

ALSmotor neuron diseaseLou Gehrig's disease

Outcome Measures

Primary Outcomes (1)

  • 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)

    during 16 weeks of test period

Secondary Outcomes (7)

  • Treatment Phase: time to event

    during 16 weeks of test period

  • Treatment Phase: %Functional Vital Capacity (FVC)

    during 16 weeks of test period

  • Treatment Phase: homocystein

    during 16 weeks of test period

  • Treatment Phase: Manual Muscle Testing (MMT)

    during 16 weeks of test period

  • Treatment Phase: Norris scale

    during 16 weeks of test period

  • +2 more secondary outcomes

Other Outcomes (7)

  • Treatment Phase: safety

    during 16 weeks of test period

  • OLE Phase: time to event

    up to 6 years 11 months

  • OLE Phase: ALSFRS-R

    up to 6 years 11 months

  • +4 more other outcomes

Study Arms (4)

Treatment Phase: Placebo

PLACEBO COMPARATOR

intramuscular injection of saline solution

Drug: saline solution

Treatment Phase: methylcobalamin

ACTIVE COMPARATOR

intramuscular injection of methylcobalamin

Drug: methylcobalamin

OLE Phase: methylcobalamin

EXPERIMENTAL

intramuscular injection of methylcobalamin

Drug: methylcobalamin

Tsunagi Phase: methylcobalamin

EXPERIMENTAL

intramuscular injection of methylcobalamin

Drug: methylcobalamin

Interventions

methylcobalaminDRUG

Patients receive methylcobalamin 50mg intramuscular injection twice a week.

OLE Phase: methylcobalaminTreatment Phase: methylcobalaminTsunagi Phase: methylcobalamin
saline solutionDRUG

Patients receive saline solution intramuscular injection twice a week.

Treatment Phase: Placebo

Eligibility Criteria

Age20 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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
  • 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:
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (16)

Nagoya University Hospital

Nagoya, Aichi-ken, 466-8560, Japan

Location

Miyoshi Neurological Clinic

Miyoshi, Hiroshima, 728-0013, Japan

Location

Sapporo Medical University Hospital

Sapporo, Hokkaido, 060-8543, Japan

Location

Kobe Central Munincipal Medical center

Kobe, Hyōgo, 650-0047, Japan

Location

Ioh National Hospital

Kanazawa, Ishikawa-ken, 920-0192, Japan

Location

Kitasato University East Hospital

Sagamihara, Kanagawa, 252-0380, Japan

Location

Shiga Medical University Hospital

Ōtsu, Shiga, 520-2192, Japan

Location

Chiba University Hospital

Chiba, 260-8677, Japan

Location

Murakami Karindo Hospital

Fukuoka, 819-8585, Japan

Location

Okayama University Hospital

Okayama, 770-8558, Japan

Location

Tokushima University Hospital

Tokushima, 770-8503, Japan

Location

Juntendo University Hospital

Tokyo, 113-8431, Japan

Location

Toho University Hospital

Tokyo, 143-8541, Japan

Location

Teikyo University Hospital

Tokyo, 173-8606, Japan

Location

Tokyo Metropolitan Neurological Hospital

Tokyo, 183-0042, Japan

Location

Wakayama Medical University Hospital

Wakayama, 641-8509, Japan

Location

Related Publications (4)

  • 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.

    PMID: 25982504RESULT

  • 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.

    PMID: 9843082RESULT

  • 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.

    PMID: 35532908DERIVED

  • 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.

    PMID: 30578206DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral SclerosisMotor Neuron Disease

Interventions

mecobalaminSaline Solution

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesNeurodegenerative DiseasesTDP-43 ProteinopathiesNeuromuscular DiseasesProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Crystalloid SolutionsIsotonic SolutionsSolutionsPharmaceutical Preparations

Study Officials

  • Ryuji Kaji, MD

    Tokushima University Hospital

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: double-blinded randomized controlled
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 14, 2018

First Posted

June 7, 2018

Study Start

November 1, 2017

Primary Completion

February 14, 2020

Study Completion

February 18, 2025

Last Updated

March 26, 2025

Record last verified: 2025-02

Data Sharing

IPD Sharing
Will share

anonymous data are available

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
Time Frame
from October 1, 2017 till March 31, 2020
Access Criteria
those who have approval from Institutional Review Board (IRB)
More information

Locations

JP(16)