Clinical Trial of Ultra-high Dose Methylcobalamin for ALS

Study Overview
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Brief Summary
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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.

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

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Drug: methylcobalamin
* Drug: saline solution


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 20 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double-blinded randomized controlled
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>intramuscular injection of saline solution | Drug: saline solution<br>* Patients receive saline solution intramuscular injection twice a week.<br>|
| Active Comparator: methylcobalamin<br>intramuscular injection of methylcobalamin | Drug: methylcobalamin<br>* Patients receive methylcobalamin 50mg intramuscular injection twice a week.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 weks of test period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| survival | time period from drug assignment to death or becoming bound to respirator | during 16 weeks of test period | 
| %Functional Vital Capacity (FVC) | changes of per cent Functional Vital Capacity | during 16 weeks of test period | 
| homocystein | changes of serum levels of homocystein | during 16 weeks of test period | 
| 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) | during 16 weeks of test period | 
| Norris scale | changes of Norris scale (39 normal - 0 worst) | during 16 weeks of test period | 
| Grip Power | changes of sum of grip power in kilograms on both sides | during 16 weeks of test period | 
| 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) | during 16 weks of test period | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, motor neuron disease, Lou Gehrig's disease