Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
- Conditions
- Amyotrophic Lateral Sclerosis
- Interventions
- Drug: saline solution
- Registration Number
- NCT03548311
- Lead Sponsor
- Eisai Co., Ltd.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 130
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.
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Treatment Phase: methylcobalamin methylcobalamin intramuscular injection of methylcobalamin Treatment Phase: Placebo saline solution intramuscular injection of saline solution Tsunagi Phase: methylcobalamin methylcobalamin intramuscular injection of methylcobalamin OLE Phase: methylcobalamin methylcobalamin intramuscular injection of methylcobalamin
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Treatment Phase: %Functional Vital Capacity (FVC) during 16 weeks of test period changes of per cent Functional Vital Capacity
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)
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: 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: homocystein during 16 weeks of test period changes of serum levels of homocystein
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
Trial Locations
- Locations (16)
Chiba University Hospital
🇯🇵Chiba, Japan
Okayama University Hospital
🇯🇵Okayama, Japan
Nagoya University Hospital
🇯🇵Nagoya, Aichi, Japan
Sapporo Medical University Hospital
🇯🇵Sapporo, Hokkaido, Japan
Ioh National Hospital
🇯🇵Kanazawa, Ishikawa, Japan
Tokushima University Hospital
🇯🇵Tokushima, Japan
Tokyo Metropolitan Neurological Hospital
🇯🇵Tokyo, Japan
Miyoshi Neurological Clinic
🇯🇵Miyoshi, Hiroshima, Japan
Kobe Central Munincipal Medical center
🇯🇵Kobe, Hyogo, Japan
Kitasato University East Hospital
🇯🇵Sagamihara, Kanagawa, Japan
Murakami Karindo Hospital
🇯🇵Fukuoka, Japan
Toho University Hospital
🇯🇵Tokyo, Japan
Shiga Medical University Hospital
🇯🇵Otsu, Shiga, Japan
Juntendo University Hospital
🇯🇵Tokyo, Japan
Teikyo University Hospital
🇯🇵Tokyo, Japan
Wakayama Medical University Hospital
🇯🇵Wakayama, Japan