UMIN-CTR Clinical Trial

Basic information
Public title	A multicentre trial of KN01 in patients with mitochondrial encephalomyopathy (MELAS)
Acronym	MELAS-taurine study
Scientific Title	A multicentre trial of KN01 in patients with mitochondrial encephalomyopathy (MELAS)
Scientific Title:Acronym	MELAS-taurine study
Region	Japan

Condition
Condition	motochondrial encephalomyopathy (MELAS)
Classification by specialty	Neurology
Classification by malignancy	Others
Genomic information	YES

Objectives
Narrative objectives1	To investigate the effocacy and safety of taurine supplementation therapy for prevention of stroke-like episodes in patients with MELAS
Basic objectives2	Safety,Efficacy
Basic objectives -Others
Trial characteristics_1	Confirmatory
Trial characteristics_2
Developmental phase	Phase III

Assessment
Primary outcomes	(1) efficacy: 100% respondor rate (2) safety: adverse events and adverse effects
Key secondary outcomes	(1) Japan Mitochondrial Disease Rating Scale (2) 50% responder rate (3) the number of abrupt-onset focal neurological deficits (4) the levels of lactate, pyruvate and taurine in the blood and CSF (5) brain MRI study (6) the number of uses intravenous formulation with L-arginine (7) the number of times in which high intensity lesions detected by brain MRI

Base
Study type	Interventional

Study design
Basic design	Single arm
Randomization	Non-randomized
Randomization unit
Blinding	Open -no one is blinded
Control	Uncontrolled
Stratification
Dynamic allocation
Institution consideration
Blocking
Concealment

Intervention
No. of arms	1
Purpose of intervention	Prevention
Type of intervention	Medicine
Interventions/Control_1	taurine supplementation
Interventions/Control_2
Interventions/Control_3
Interventions/Control_4
Interventions/Control_5
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	Not applicable
Age-upper limit	Not applicable
Gender	Male and Female
Key inclusion criteria	(1) patients comprehensively diagnosed with MELAS based on clinical manifestations, muscle pathological findings, and genetic testing, as followed by the diagnostic criteria of MELAS (2) patients with point mutations of either A3243G, T3271C, G3244A, T3258C, or T3291C in the mitochondrial DNA (3) age at the time of obtaining informed consent , gender , hospitalization or outpatient are unquestioned (4) patients not using arginine for 78 weeks before obtaining informed consent, or patients continuously using arginine for at least 26 weeks before obtaining informed consent (5) patients who meet any of the following: 1) patients without arginine use should have stroke-like episodes more than twice in 78 weeks and more than once in 52 weeks before obtaining informed consent (no arginine combination cases ) 2) patients with arginine use who meet any of the following, depending on the period of arginine use (arginine combination cases) If (i) arginine use period within 78 weeks, patients should have stroke-like episodes more than twice in the period of use and at least more than once in 52 weeks before obtaining informed consent If (ii) arginine use period exceeds 78 weeks, patients should have stroke-like episodes more than twice in 78 weeks and at least more than once in 52 weeks before obtaining informed consent The definition of stroke-like episodes in the selection criteria , includes any of the following paroxysmal focal neurological symptoms of 1) ~ 6), and the implementation of the head MRI does not matter . 1) hemiparesis or monoparesis 2) cortical sensory impairment ( sensory extinction ) 3) cortical visual impairment (scintilating scotoma, cortical blindness) 4) aphasia 5) apraxia 6) agnosia (6) patient that has not been treated with oral taurine supplementation (7) patient capable of being evaluated by clinical findings of stroke-like episodes
Key exclusion criteria	(1) patients can not be conducted by head MRI scan because of pacemaker implantation, etc. (2) patients with severe coma or status epileptics (3) patients incapable of communication due to dementia, bedridden, etc., (4) patients with merger sepsis (5) patients with severe impairment in cardiac, liver, or renal function (6) patients in need of systemic administration of steroids for a long period of time (2 weeks or more) (7) patients with pyruvate in 12 weeks before obtaining informed consent (8) patients who are pregnant or lactating, or may be pregnant (9) patients with history of hypersensitivity to the component of study drug (10) patients with history of drug allergy (11) patients who participated in clinical trials within 12 weeks before obtaining informed consent (12) other, patients whom physician or investigator has determined disqualified as participants
Target sample size	15

Research contact person
Name of lead principal investigator	1st name Middle name Last name Yoshihide Sunada
Organization	Kawasaki Medical School
Division name	Neurology
Zip code
Address	577 Matsushima,Kurashiki-city,Okayama 701-0192 Japan
TEL	086-462-1111
Email	ysunada@med.kawasaki-m.ac.jp

Public contact
Name of contact person	1st name Middle name Last name Mai Moriyama
Organization	CTD inc.
Division name	Medicinal Products Promotion Division
Zip code
Address	3-3-2, Tsukiji, Chuo-ku, Tokyo
TEL	03-6228-4105
Homepage URL	https://www.c-ctd.co.jp/project_sn01/researcher/contents/documents.html
Email	taurine@c-ctd.co.jp

Sponsor
Institute	Kawasaki Medical School Hospital
Institute
Department

Funding Source
Organization	Ministry of Health, Labour and Welfare
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor	National Defense Medical College Hospital Seirei Hamamatsu General Hospital Fujita Health University School of Medicine National Hospital Organization Kyoto Medical Center Hyogo-Chuo National Hospital Fukuoka University Chikushi Hospital Kurume University Hospital Nagasaki University Hospital Hiroshima University Hospital Nippon Medical School National Center of Neurology and Psychiatry Teikyo University of Science
Name of secondary funder(s)

IRB Contact (For public release)
Organization
Address
Tel
Email

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW	9月13日

Institutions

Institutions

川崎医科大学附属病院/Kawasaki Medical School 防衛医科大学校病院/National Defense Medical College Hospital 聖隷浜松病院/Seirei Hamamatsu General Hospital 藤田保健衛生大学病院/Fujita Health University School of Medicine 独立行政法人国立病院機構京都医療センター/National Hospital Organization Kyoto Medical Center 独立行政法人国立病院機構兵庫中央病院/Hyogo-Chuo National Hospital 福岡大学筑紫病院/Fukuoka University Chikushi Hospital 久留米大学医学部附属病院/Kurume University Hospital 長崎大学病院/Nagasaki University Hospital 広島大学病院/Hiroshima University Hospital

Other administrative information
Date of disclosure of the study information	2013 Year 09 Month 30 Day

Related information
URL releasing protocol	https://www.c-ctd.co.jp/project_sn01/researcher/contents/documents.html
Publication of results	Unpublished

Result
URL related to results and publications
Number of participants that the trial has enrolled
Results	Look at the attached file, "clinical trial report"
Results date posted
Results Delayed
Results Delay Reason
Date of the first journal publication of results
Baseline Characteristics
Participant flow
Adverse events
Outcome measures
Plan to share IPD
IPD sharing Plan description

Progress
Recruitment status	Completed
Date of protocol fixation	2013 Year 07 Month 24 Day
Date of IRB
Anticipated trial start date	2013 Year 10 Month 03 Day
Last follow-up date	2015 Year 01 Month 09 Day
Date of closure to data entry
Date trial data considered complete
Date analysis concluded	2015 Year 03 Month 31 Day

Other
Other related information

Management information
Registered date	2013 Year 09 Month 30 Day
Last modified on	2019 Year 02 Month 25 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013908

Research Plan
Registered date	File name
2017/11/04	Protocol.pdf

Research case data specifications
Registered date	File name

Research case data
Registered date	File name
2017/11/04	ClinicalTrialReport.pdf

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