Clinical Trial of Ultra-high Dose Methylcobalamin for ALS

Amyotrophic Lateral Sclerosis Clinical Trial

— JETALS  

Official title:

Japanese Early-stage Clinical Trial of Ultra-high Dose Methylcobalamin for Amyotrophic Lateral Sclerosis: a Pivotal Phase 3 Randomized Controlled Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03548311
• Other study ID #: 763
• Status: Recruiting
• Phase: Phase 3
• Start date: November 1, 2017
• Est. completion date: March 31, 2020

Study information

• Verified date: June 2018
• Source: University of Tokushima
• Contact: Yuisin Izumi, MD
• Phone: 81-88-633-7207
• Email: yizumi[@]tokushima-u.ac.jp
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 128
• Est. completion date: March 31, 2020
• Est. primary completion date: February 28, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• methylcobalamin
Patients receive methylcobalamin 50mg intramuscular injection twice a week.
• saline solution
Patients receive saline solution intramuscular injection twice a week.

Locations

Country	Name	City	State
Japan	Chiba University Hospital	Chiba
Japan	Murakami Karindo Hospital	Fukuoka
Japan	Ioh National Hospital	Kanazawa	Ishikawa
Japan	Kobe Central Munincipal Medical center	Kobe	Hyogo
Japan	Miyoshi Neurological Clinic	Miyoshi	Hiroshima
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Okayama University Hospital	Okayama
Japan	Shiga Medical University Hospital	Otsu	Shiga
Japan	Kitasato University East Hospital	Sagamihara	Kanagawa
Japan	Sapporo Medical University Hospital	Sapporo	Hokkaido
Japan	Tokushima University Hospital	Tokushima
Japan	Juntendo University Hospital	Tokyo
Japan	Teikyo University Hospital	Tokyo
Japan	Toho University Hospital	Tokyo
Japan	Tokyo Metropolitan Neurological Hospital	Tokyo
Japan	Wakayama Medical University Hospital	Wakayama

Sponsors (2)

Lead Sponsor	Collaborator
University of Tokushima	Eisai Co., Ltd.

Country where clinical trial is conducted

Japan, 

References & Publications (2)

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. — View 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):17 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	safety	any adverse events during the study period	during 16 weks of test period
Primary	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 weks of test period
Secondary	survival	time period from drug assignment to death or becoming bound to respirator	during 16 weeks of test period
Secondary	%Functional Vital Capacity (FVC)	changes of per cent Functional Vital Capacity	during 16 weeks of test period
Secondary	homocystein	changes of serum levels of homocystein	during 16 weeks of test period
Secondary	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
Secondary	Norris scale	changes of Norris scale (39 normal - 0 worst)	during 16 weeks of test period
Secondary	Grip Power	changes of sum of grip power in kilograms on both sides	during 16 weeks of test period
Secondary	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 weks of test period