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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status
Unknown status
Phase
Phase 3
Locations
Japan
Study Type
Interventional
Intervention
methylcobalamin
saline solution
Sponsored by
University of Tokushima
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring ALS, motor neuron disease, Lou Gehrig's disease

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Nagoya University HospitalRecruiting
  • Miyoshi Neurological ClinicRecruiting
  • Sapporo Medical University HospitalRecruiting
  • Kobe Central Munincipal Medical centerRecruiting
  • Ioh National HospitalRecruiting
  • Kitasato University East HospitalRecruiting
  • Shiga Medical University HospitalRecruiting
  • Chiba University HospitalRecruiting
  • Murakami Karindo HospitalRecruiting
  • Okayama University HospitalRecruiting
  • Tokushima University HospitalRecruiting
  • Juntendo University HospitalRecruiting
  • Toho University HospitalRecruiting
  • Teikyo University HospitalRecruiting
  • Tokyo Metropolitan Neurological HospitalRecruiting
  • Wakayama Medical University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Placebo

methylcobalamin

Arm Description

intramuscular injection of saline solution

intramuscular injection of methylcobalamin

Outcomes

Primary Outcome Measures

ALSFRS-R
Drop of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (maximum or normal 48 and minimum 0; higher values represent better condition)

Secondary Outcome Measures

survival
time period from drug assignment to death or becoming bound to respirator
%Functional Vital Capacity (FVC)
changes of per cent Functional Vital Capacity
homocystein
changes of serum levels of homocystein
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)
Norris scale
changes of Norris scale (39 normal - 0 worst)
Grip Power
changes of sum of grip power in kilograms on both sides
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)

Full Information

First Posted
May 14, 2018
Last Updated
June 21, 2018
Sponsor
University of Tokushima
Collaborators
Eisai Co., Ltd.
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1. Study Identification

Unique Protocol Identification Number
NCT03548311
Brief Title
Clinical Trial of Ultra-high Dose Methylcobalamin for ALS
Acronym
JETALS
Official Title
Japanese Early-stage Clinical Trial of Ultra-high Dose Methylcobalamin for Amyotrophic Lateral Sclerosis: a Pivotal Phase 3 Randomized Controlled Study
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Unknown status
Study Start Date
November 1, 2017 (Actual)
Primary Completion Date
February 28, 2020 (Anticipated)
Study Completion Date
March 31, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Tokushima
Collaborators
Eisai Co., Ltd.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
ALS, motor neuron disease, Lou Gehrig's disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
double-blinded randomized controlled
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
128 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
intramuscular injection of saline solution
Arm Title
methylcobalamin
Arm Type
Active Comparator
Arm Description
intramuscular injection of methylcobalamin
Intervention Type
Drug
Intervention Name(s)
methylcobalamin
Intervention Description
Patients receive methylcobalamin 50mg intramuscular injection twice a week.
Intervention Type
Drug
Intervention Name(s)
saline solution
Intervention Description
Patients receive saline solution intramuscular injection twice a week.
Primary Outcome Measure Information:
Title
ALSFRS-R
Description
Drop of Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (maximum or normal 48 and minimum 0; higher values represent better condition)
Time Frame
during 16 weks of test period
Secondary Outcome Measure Information:
Title
survival
Description
time period from drug assignment to death or becoming bound to respirator
Time Frame
during 16 weeks of test period
Title
%Functional Vital Capacity (FVC)
Description
changes of per cent Functional Vital Capacity
Time Frame
during 16 weeks of test period
Title
homocystein
Description
changes of serum levels of homocystein
Time Frame
during 16 weeks of test period
Title
Manual Muscle Testing (MMT)
Description
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)
Time Frame
during 16 weeks of test period
Title
Norris scale
Description
changes of Norris scale (39 normal - 0 worst)
Time Frame
during 16 weeks of test period
Title
Grip Power
Description
changes of sum of grip power in kilograms on both sides
Time Frame
during 16 weeks of test period
Title
40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40)
Description
changes of sum of ALSAQ-40 (40-item Amyotrophic Lateral Sclerosis Assessment Questionnaire) score (40 normal - 200 worst)
Time Frame
during 16 weks of test period
Other Pre-specified Outcome Measures:
Title
safety
Description
any adverse events during the study period
Time Frame
during 16 weks of test period

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Yuisin Izumi, MD
Phone
81-88-633-7207
Email
yizumi@tokushima-u.ac.jp
First Name & Middle Initial & Last Name or Official Title & Degree
Ryosuke Oki, MD
Phone
81-88-633-9658
Email
oki.ryosuke@tokushima-u.ac.jp
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ryuji Kaji, MD
Organizational Affiliation
Tokushima University Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Nagoya University Hospital
City
Nagoya
State/Province
Aichi
ZIP/Postal Code
466-8560
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Naoki Atsuta, MD
Phone
81-52-741-2111
Facility Name
Miyoshi Neurological Clinic
City
Miyoshi
State/Province
Hiroshima
ZIP/Postal Code
728-0013
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Masaya Oda, MD
Facility Name
Sapporo Medical University Hospital
City
Sapporo
State/Province
Hokkaido
ZIP/Postal Code
060-8543
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shun Shimohama, MD
Phone
81-11-611-2111
Facility Name
Kobe Central Munincipal Medical center
City
Kobe
State/Province
Hyogo
ZIP/Postal Code
650-0047
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nobuo Kohara, MD
Phone
81-78-302-4321
Facility Name
Ioh National Hospital
City
Kanazawa
State/Province
Ishikawa
ZIP/Postal Code
920-0192
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kiyonobu Komai, MD
Phone
81-76-258-1180
Facility Name
Kitasato University East Hospital
City
Sagamihara
State/Province
Kanagawa
ZIP/Postal Code
252-0380
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Makiko Nagai, MD
Phone
81-42-748-9111
Facility Name
Shiga Medical University Hospital
City
Otsu
State/Province
Shiga
ZIP/Postal Code
520-2192
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Makoto Urushidani, MD
Phone
81-77-548-2111
Facility Name
Chiba University Hospital
City
Chiba
ZIP/Postal Code
260-8677
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Satoshi Kuwabara, MD
Phone
81-43-222-7171
Email
kuwabara-s@faculty.chiba-u.jp
Facility Name
Murakami Karindo Hospital
City
Fukuoka
ZIP/Postal Code
819-8585
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hitoshi Kikuchi, MD
Phone
81-92-811-3331
Facility Name
Okayama University Hospital
City
Okayama
ZIP/Postal Code
770-8558
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Koji Abe, MD
Phone
88-86-223-7151
Email
abekabek@cc.okayama-u.ac.jp
Facility Name
Tokushima University Hospital
City
Tokushima
ZIP/Postal Code
770-8503
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hiroyuki Nodera, MD
Phone
81-88-633-9658
Email
hnodera@tokushima-u.ac.jp
Facility Name
Juntendo University Hospital
City
Tokyo
ZIP/Postal Code
113-8431
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kazuaki Kanai, MD
Facility Name
Toho University Hospital
City
Tokyo
ZIP/Postal Code
143-8541
Country
Japan
Individual Site Status
Recruiting
Facility Name
Teikyo University Hospital
City
Tokyo
ZIP/Postal Code
173-8606
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Masahiro Sonoo, MD
Facility Name
Tokyo Metropolitan Neurological Hospital
City
Tokyo
ZIP/Postal Code
183-0042
Country
Japan
Individual Site Status
Recruiting
Facility Name
Wakayama Medical University Hospital
City
Wakayama
ZIP/Postal Code
641-8509
Country
Japan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hidefumi Ito, MD
Phone
81-73-447-2300

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
anonymous data are available
IPD Sharing Time Frame
from October 1, 2017 till March 31, 2020
IPD Sharing Access Criteria
those who have approval from Institutional Review Board (IRB)
IPD Sharing URL
http://als-mecobalamin.org
Citations:
PubMed Identifier
25982504
Citation
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.
Results Reference
result
PubMed Identifier
9843082
Citation
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.
Results Reference
result
PubMed Identifier
35532908
Citation
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.
Results Reference
derived
PubMed Identifier
30578206
Citation
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.
Results Reference
derived

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Clinical Trial of Ultra-high Dose Methylcobalamin for ALS

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