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Clinical Trial of Ultra-high Dose Methylcobalamin for ALS (JETALS)

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ClinicalTrials.gov Identifier: NCT03548311
Recruitment Status : Recruiting
First Posted : June 7, 2018
Last Update Posted : June 25, 2018
Sponsor:
Collaborator:
Eisai Co., Ltd.
Information provided by (Responsible Party):
Ryuji Kaji, University of Tokushima

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 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.

Condition or disease Intervention/treatment Phase
Amyotrophic Lateral Sclerosis Drug: methylcobalamin Drug: saline solution Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 128 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: double-blinded randomized controlled
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Japanese Early-stage Clinical Trial of Ultra-high Dose Methylcobalamin for Amyotrophic Lateral Sclerosis: a Pivotal Phase 3 Randomized Controlled Study
Actual Study Start Date : November 1, 2017
Estimated Primary Completion Date : February 28, 2020
Estimated Study Completion Date : March 31, 2020


Arm Intervention/treatment
Placebo Comparator: Placebo
intramuscular injection of saline solution
Drug: saline solution
Patients receive saline solution intramuscular injection twice a week.

Active Comparator: methylcobalamin
intramuscular injection of methylcobalamin
Drug: methylcobalamin
Patients receive methylcobalamin 50mg intramuscular injection twice a week.




Primary Outcome Measures :
  1. ALSFRS-R [ Time Frame: during 16 weks 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 :
  1. survival [ Time Frame: during 16 weeks of test period ]
    time period from drug assignment to death or becoming bound to respirator

  2. %Functional Vital Capacity (FVC) [ Time Frame: during 16 weeks of test period ]
    changes of per cent Functional Vital Capacity

  3. homocystein [ Time Frame: during 16 weeks of test period ]
    changes of serum levels of homocystein

  4. 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. Norris scale [ Time Frame: during 16 weeks of test period ]
    changes of Norris scale (39 normal - 0 worst)

  6. Grip Power [ Time Frame: during 16 weeks of test period ]
    changes of sum of grip power in kilograms on both sides

  7. 40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) [ Time Frame: during 16 weks of test period ]
    changes of sum of ALSAQ-40 (40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire) score (40 normal - 200 worst)


Other Outcome Measures:
  1. safety [ Time Frame: during 16 weks of test period ]
    any adverse events during the study period



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Ages Eligible for Study:   20 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03548311


Contacts
Contact: Yuisin Izumi, MD 81-88-633-7207 yizumi@tokushima-u.ac.jp
Contact: Ryosuke Oki, MD 81-88-633-9658 oki.ryosuke@tokushima-u.ac.jp

Locations
Japan
Nagoya University Hospital Recruiting
Nagoya, Aichi, Japan, 466-8560
Contact: Naoki Atsuta, MD    81-52-741-2111      
Miyoshi Neurological Clinic Recruiting
Miyoshi, Hiroshima, Japan, 728-0013
Contact: Masaya Oda, MD         
Sapporo Medical University Hospital Recruiting
Sapporo, Hokkaido, Japan, 060-8543
Contact: Shun Shimohama, MD    81-11-611-2111      
Kobe Central Munincipal Medical center Recruiting
Kobe, Hyogo, Japan, 650-0047
Contact: Nobuo Kohara, MD    81-78-302-4321      
Ioh National Hospital Recruiting
Kanazawa, Ishikawa, Japan, 920-0192
Contact: Kiyonobu Komai, MD    81-76-258-1180      
Kitasato University East Hospital Recruiting
Sagamihara, Kanagawa, Japan, 252-0380
Contact: Makiko Nagai, MD    81-42-748-9111      
Shiga Medical University Hospital Recruiting
Otsu, Shiga, Japan, 520-2192
Contact: Makoto Urushidani, MD    81-77-548-2111      
Chiba University Hospital Recruiting
Chiba, Japan, 260-8677
Contact: Satoshi Kuwabara, MD    81-43-222-7171    kuwabara-s@faculty.chiba-u.jp   
Murakami Karindo Hospital Recruiting
Fukuoka, Japan, 819-8585
Contact: Hitoshi Kikuchi, MD    81-92-811-3331      
Okayama University Hospital Recruiting
Okayama, Japan, 770-8558
Contact: Koji Abe, MD    88-86-223-7151    abekabek@cc.okayama-u.ac.jp   
Tokushima University Hospital Recruiting
Tokushima, Japan, 770-8503
Contact: Hiroyuki Nodera, MD    81-88-633-9658    hnodera@tokushima-u.ac.jp   
Juntendo University Hospital Recruiting
Tokyo, Japan, 113-8431
Contact: Kazuaki Kanai, MD         
Toho University Hospital Recruiting
Tokyo, Japan, 143-8541
Teikyo University Hospital Recruiting
Tokyo, Japan, 173-8606
Contact: Masahiro Sonoo, MD         
Tokyo Metropolitan Neurological Hospital Recruiting
Tokyo, Japan, 183-0042
Wakayama Medical University Hospital Recruiting
Wakayama, Japan, 641-8509
Contact: Hidefumi Ito, MD    81-73-447-2300      
Sponsors and Collaborators
University of Tokushima
Eisai Co., Ltd.
Investigators
Study Director: Ryuji Kaji, MD Tokushima University Hospital

Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Ryuji Kaji, Professor of Neurology, University of Tokushima
ClinicalTrials.gov Identifier: NCT03548311     History of Changes
Other Study ID Numbers: 763
First Posted: June 7, 2018    Key Record Dates
Last Update Posted: June 25, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: anonymous data are available
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: from October 1, 2017 till March 31, 2020
Access Criteria: those who have approval from Institutional Review Board (IRB)
URL: http://als-mecobalamin.org

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Ryuji Kaji, University of Tokushima:
ALS
motor neuron disease
Lou Gehrig's disease

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases
Pharmaceutical Solutions
Vitamin B 12
Vitamin B Complex
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs