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

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ClinicalTrials.gov Identifier: NCT03548311

Recruitment Status : Unknown

Verified June 2018 by Ryuji Kaji, University of Tokushima.
Recruitment status was: Recruiting

First Posted : June 7, 2018

Last Update Posted : June 26, 2018

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborator:

Eisai Co., Ltd.

Information provided by (Responsible Party):

Ryuji Kaji, University of Tokushima

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.

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

Study Design

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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

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Amyotrophic lateral sclerosis Juvenile primary lateral sclerosis

MedlinePlus related topics: Amyotrophic Lateral Sclerosis

Drug Information available for: Cyanocobalamin Cobalamin Mecobalamin

Genetic and Rare Diseases Information Center resources: Primary Lateral Sclerosis Amyotrophic Lateral Sclerosis

U.S. FDA Resources

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

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 :

survival [ Time Frame: during 16 weeks of test period ]
time period from drug assignment to death or becoming bound to respirator
%Functional Vital Capacity (FVC) [ Time Frame: during 16 weeks of test period ]
changes of per cent Functional Vital Capacity
homocystein [ Time Frame: during 16 weeks of test period ]
changes of serum levels of homocystein
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)
Norris scale [ Time Frame: during 16 weeks of test period ]
changes of Norris scale (39 normal - 0 worst)
Grip Power [ Time Frame: during 16 weeks of test period ]
changes of sum of grip power in kilograms on both sides
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:

safety [ Time Frame: during 16 weks of test period ]
any adverse events during the study period

Eligibility Criteria

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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

Contacts and Locations

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

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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

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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

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Study Director:	Ryuji Kaji, MD	Tokushima University Hospital

More Information

Publications of Results:

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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Responsible Party:	Ryuji Kaji, Professor of Neurology, University of Tokushima
ClinicalTrials.gov Identifier:	NCT03548311
Other Study ID Numbers:	763
First Posted:	June 7, 2018 Key Record Dates
Last Update Posted:	June 26, 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

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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:

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Motor Neuron Disease Amyotrophic Lateral Sclerosis Sclerosis Pathologic Processes Neurodegenerative Diseases Nervous System Diseases Neuromuscular Diseases Spinal Cord Diseases Central Nervous System Diseases	TDP-43 Proteinopathies Proteostasis Deficiencies Metabolic Diseases Vitamin B 12 Vitamin B Complex Vitamins Micronutrients Physiological Effects of Drugs

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