JETALS: Clinical Trial of Ultra-high Dose Methylcobalamin for ALS

Sponsor

University of Tokushima (Other)

Overall Status

Unknown status

CT.gov ID

NCT03548311

Collaborator

Eisai Co., Ltd. (Industry)

128

Enrollment

Locations

Arms

28.9

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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

Study Type:

Interventional

Anticipated Enrollment :

128 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

double-blinded randomized controlleddouble-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 :

Nov 1, 2017

Anticipated Primary Completion Date :

Feb 28, 2020

Anticipated Study Completion Date :

Mar 31, 2020

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.

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 [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 [during 16 weeks of test period]
time period from drug assignment to death or becoming bound to respirator
%Functional Vital Capacity (FVC) [during 16 weeks of test period]
changes of per cent Functional Vital Capacity
homocystein [during 16 weeks of test period]
changes of serum levels of homocystein
Manual Muscle Testing (MMT) [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 [during 16 weeks of test period]
changes of Norris scale (39 normal - 0 worst)
Grip Power [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) [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 [during 16 weks of test period]
any adverse events during the study period

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years and Older

Sexes Eligible for Study:

All

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Nagoya University Hospital	Nagoya	Aichi	Japan	466-8560
2	Miyoshi Neurological Clinic	Miyoshi	Hiroshima	Japan	728-0013
3	Sapporo Medical University Hospital	Sapporo	Hokkaido	Japan	060-8543
4	Kobe Central Munincipal Medical center	Kobe	Hyogo	Japan	650-0047
5	Ioh National Hospital	Kanazawa	Ishikawa	Japan	920-0192
6	Kitasato University East Hospital	Sagamihara	Kanagawa	Japan	252-0380
7	Shiga Medical University Hospital	Otsu	Shiga	Japan	520-2192
8	Chiba University Hospital	Chiba		Japan	260-8677
9	Murakami Karindo Hospital	Fukuoka		Japan	819-8585
10	Okayama University Hospital	Okayama		Japan	770-8558
11	Tokushima University Hospital	Tokushima		Japan	770-8503
12	Juntendo University Hospital	Tokyo		Japan	113-8431
13	Toho University Hospital	Tokyo		Japan	143-8541
14	Teikyo University Hospital	Tokyo		Japan	173-8606
15	Tokyo Metropolitan Neurological Hospital	Tokyo		Japan	183-0042
16	Wakayama Medical University Hospital	Wakayama		Japan	641-8509