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| Name | Class |
|---|---|
| University of Tokushima | OTHER |
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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 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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Treatment Phase: Placebo | Placebo Comparator | intramuscular injection of saline solution |
|
| Treatment Phase: methylcobalamin | Active Comparator | intramuscular injection of methylcobalamin |
|
| OLE Phase: methylcobalamin | Experimental | intramuscular injection of methylcobalamin |
|
| Tsunagi Phase: methylcobalamin | Experimental | intramuscular injection of methylcobalamin |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| methylcobalamin | Drug | Patients receive methylcobalamin 50mg intramuscular injection twice a week. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment Phase: time to event | 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) | during 16 weeks of test period |
| Treatment Phase: %Functional Vital Capacity (FVC) |
| Measure | Description | Time Frame |
|---|---|---|
| Treatment Phase: safety | any adverse events during the treatment period | during 16 weeks of test period |
| OLE Phase: time to event | 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) |
Inclusion Criteria:
Treatment and OLE Phase:
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:
Tsunagi Phase:
Not applicable.
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| Name | Affiliation | Role |
|---|---|---|
| Ryuji Kaji, MD | Tokushima University Hospital | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Nagoya University Hospital | Nagoya | Aichi-ken | 466-8560 | Japan | ||
| Miyoshi Neurological Clinic |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25982504 | Result | 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. | |
| 9843082 | Result | 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. |
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anonymous data are available
from October 1, 2017 till March 31, 2020
those who have approval from Institutional Review Board (IRB)
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| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| D016472 | Motor Neuron Disease |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D019636 | Neurodegenerative Diseases |
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| ID | Term |
|---|---|
| C019476 | mecobalamin |
| D000077330 | Saline Solution |
| ID | Term |
|---|---|
| D000077324 | Crystalloid Solutions |
| D007552 | Isotonic Solutions |
| D012996 | Solutions |
| D004364 | Pharmaceutical Preparations |
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double-blinded randomized controlled
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| saline solution | Drug | Patients receive saline solution intramuscular injection twice a week. |
|
changes of per cent Functional Vital Capacity |
| during 16 weeks of test period |
| Treatment Phase: homocystein | changes of serum levels of homocystein | during 16 weeks of test period |
| Treatment Phase: 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 |
| Treatment Phase: Norris scale | changes of Norris scale (39 normal - 0 worst) | during 16 weeks of test period |
| Treatment Phase: Grip Power | changes of sum of grip power in kilograms on both sides | during 16 weeks of test period |
| Treatment Phase: 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 weeks of test period |
| up to 6 years 11 months |
| OLE Phase: ALSFRS-R | Drop of ALSFRS-R Scale-Revised (maximum or normal 48 and minimum 0; higher values represent better condition) | up to 6 years 11 months |
| OLE Phase: safety | any adverse events during the OLE period including laboratory tests and vital signs assessment. | up to 6 years 11 months |
| Tsunagi Phase: time to event | time period from drug assignment to any of the event (24-hour use of noninvasive respiratory support, use of invasive respiratory support, or death) | up to 6 months |
| Tsunagi Phase: ALSFRS-R | Drop of ALSFRS-R Scale-Revised (maximum or normal 48 and minimum 0; higher values represent better condition) | up to 6 months |
| Tsunagi Phase: safety | any adverse events during the Tsunagi phase including laboratory tests and vital signs assessment. | up to 6 months |
| Miyoshi |
| Hiroshima |
| 728-0013 |
| Japan |
| Sapporo Medical University Hospital | Sapporo | Hokkaido | 060-8543 | Japan |
| Kobe Central Munincipal Medical center | Kobe | Hyōgo | 650-0047 | Japan |
| Ioh National Hospital | Kanazawa | Ishikawa-ken | 920-0192 | Japan |
| Kitasato University East Hospital | Sagamihara | Kanagawa | 252-0380 | Japan |
| Shiga Medical University Hospital | Ōtsu | Shiga | 520-2192 | Japan |
| Chiba University Hospital | Chiba | 260-8677 | Japan |
| Murakami Karindo Hospital | Fukuoka | 819-8585 | Japan |
| Okayama University Hospital | Okayama | 770-8558 | Japan |
| Tokushima University Hospital | Tokushima | 770-8503 | Japan |
| Juntendo University Hospital | Tokyo | 113-8431 | Japan |
| Toho University Hospital | Tokyo | 143-8541 | Japan |
| Teikyo University Hospital | Tokyo | 173-8606 | Japan |
| Tokyo Metropolitan Neurological Hospital | Tokyo | 183-0042 | Japan |
| Wakayama Medical University Hospital | Wakayama | 641-8509 | Japan |
| 35532908 | Derived | 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. |
| 30578206 | Derived | 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. |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |