Amyotrophic Lateral Sclerosis
Conditions
Keywords
ALS, motor neuron disease, Lou Gehrig's disease
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.
Interventions
DRUGmethylcobalamin
Patients receive methylcobalamin 50mg intramuscular injection twice a week.
DRUGsaline solution
Patients receive saline solution intramuscular injection twice a week.
Sponsors
University of Tokushima
Eisai Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
double-blinded randomized controlled
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Phase: ALSFRS-R | 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
| Measure | Time frame | Description |
|---|---|---|
| Treatment Phase: time to event | 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) |
| Treatment Phase: %Functional Vital Capacity (FVC) | during 16 weeks of test period | changes of per cent Functional Vital Capacity |
| Treatment Phase: homocystein | during 16 weeks of test period | changes of serum levels of homocystein |
| Treatment Phase: Manual Muscle Testing (MMT) | 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) |
| Treatment Phase: Norris scale | during 16 weeks of test period | changes of Norris scale (39 normal - 0 worst) |
| Treatment Phase: Grip Power | during 16 weeks of test period | changes of sum of grip power in kilograms on both sides |
| Treatment Phase: 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) | 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
| Measure | Time frame | Description |
|---|---|---|
| OLE Phase: time to event | 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) |
| OLE Phase: ALSFRS-R | up to 6 years 11 months | Drop of ALSFRS-R Scale-Revised (maximum or normal 48 and minimum 0; higher values represent better condition) |
| OLE Phase: safety | up to 6 years 11 months | any adverse events during the OLE period including laboratory tests and vital signs assessment. |
| Tsunagi Phase: time to event | 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) |
| Tsunagi Phase: ALSFRS-R | up to 6 months | Drop of ALSFRS-R Scale-Revised (maximum or normal 48 and minimum 0; higher values represent better condition) |
| Tsunagi Phase: safety | up to 6 months | any adverse events during the Tsunagi phase including laboratory tests and vital signs assessment. |
| Treatment Phase: safety | during 16 weeks of test period | any adverse events during the treatment period |
Countries
Japan
Outcome results
None listed