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Completed

NCT Number: NCT03548311

Clinical Trial of Ultra-high Dose Methylcobalamin for ALS

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.

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Key information

Conditions

Amyotrophic Lateral Sclerosis Central Nervous System Diseases Metabolic Diseases Motor Neuron Disease Nervous System Diseases Neurodegenerative Diseases Neuromuscular Diseases Nutritional and Metabolic Diseases Proteostasis Deficiencies Spinal Cord Diseases TDP-43 Proteinopathies

Age range

20 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Nagoya University Hospital, Nagoya, Aichi-ken, Japan

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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.

Exclusion criteria

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:

Not applicable.

Treatment and study plan

methylcobalamin

Drug

Patients receive methylcobalamin 50mg intramuscular injection twice a week.

Saline Solution

Drug

Patients receive saline solution intramuscular injection twice a week.

Primary outcomes

  1. 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)

Secondary outcomes

  1. Treatment Phase: time to event

    Time frame: during 16 weeks of test period

    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)

  2. Treatment Phase: %Functional Vital Capacity (FVC)

    Time frame: during 16 weeks of test period

    changes of per cent Functional Vital Capacity

  3. Treatment Phase: homocystein

    Time frame: during 16 weeks of test period

    changes of serum levels of homocystein

  4. Treatment Phase: Manual Muscle Testing (MMT)

    Time frame: during 16 weeks of test period

    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)

  5. Treatment Phase: Norris scale

    Time frame: during 16 weeks of test period

    changes of Norris scale (39 normal - 0 worst)

  6. Treatment Phase: Grip Power

    Time frame: during 16 weeks of test period

    changes of sum of grip power in kilograms on both sides

  7. Treatment Phase: 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40)

    Time frame: during 16 weeks of test period

    changes of sum of ALSAQ-40 (40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire) score (40 normal - 200 worst)

Other outcomes

  1. Treatment Phase: safety

    Time frame: during 16 weeks of test period

    any adverse events during the treatment period

  2. OLE Phase: time to event

    Time frame: up to 6 years 11 months

    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)

  3. OLE Phase: ALSFRS-R

    Time frame: up to 6 years 11 months

    Drop of ALSFRS-R Scale-Revised (maximum or normal 48 and minimum 0; higher values represent better condition)

  4. OLE Phase: safety

    Time frame: up to 6 years 11 months

    any adverse events during the OLE period including laboratory tests and vital signs assessment.

  5. Tsunagi Phase: time to event

    Time frame: up to 6 months

    time period from drug assignment to any of the event (24-hour use of noninvasive respiratory support, use of invasive respiratory support, or death)

  6. Tsunagi Phase: ALSFRS-R

    Time frame: up to 6 months

    Drop of ALSFRS-R Scale-Revised (maximum or normal 48 and minimum 0; higher values represent better condition)

  7. Tsunagi Phase: safety

    Time frame: up to 6 months

    any adverse events during the Tsunagi phase including laboratory tests and vital signs assessment.

Sponsors and collaborators

Lead sponsor

Eisai Co., Ltd.

Industry

Collaborators

  • University of Tokushima

Registry information

Official study title

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

Acronym: JETALS

Important dates

Study start
2017
Primary completion
2020
Study completion
2025
First posted
Jun 7, 2018
Registry last updated
Mar 26, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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