UMIN-CTR Clinical Trial

Basic information
Official scientific title of the study	The efficacy of repeated transcranial magnetic stimulation on communication and skilled motor function of children
Title of the study (Brief title)	The efficacy of repeated transcranial magnetic stimulation on communication and skilled motor function of children
Region	Japan

Condition
Condition	autism spectrum disorder
Classification by specialty	Pediatrics
Classification by malignancy	Others
Genomic information	NO

Objectives
Narrative objectives1	To evaluate the safety and the effect of repeated transcranial magnetic stimulation (rTMS) on social and motor function of children with autism spectrum disorder
Basic objectives2	Efficacy
Basic objectives -Others
Trial characteristics_1	Exploratory
Trial characteristics_2	Pragmatic
Developmental phase	Not applicable

Assessment
Primary outcomes	1. Outcome for efficacy (evaluated on the day when rTMS is performed) a. coordinated upper limb movement evaluated by Trace Coder b. Motor evoked potential c. Sociocognitive function evaluated by GazeFinder 2. Outcome for safety a. the occurrence of adverse events and their extent
Key secondary outcomes	1. Outcome for efficacy (evaluated on the day when rTMS is performed) Global motor function evaluated by movement assessment battery for children 2 (M-ABC2) 2. Outcome for saftey The occurrence of severe adverse events at each site of stimulation

Base
Study type	Interventional

Study design
Basic design	Cross-over
Randomization	Randomized
Randomization unit	Individual
Blinding	Single blind -participants are blinded
Control	Placebo
Stratification	NO
Dynamic allocation	NO
Institution consideration	Institution is not considered as adjustment factor.
Blocking	NO
Concealment	Pseudo-randomization

Intervention
No. of arms	5
Purpose of intervention	Treatment
Type of intervention	Device,equipment
Interventions/Control_1	Repeated transcranial magnetic stimulation (rTMS) with intensity of 90% of resting motor threshold and 900 pulses for one session was given to the following brain regions in the following order at the low frequency (1 Hz). Regarding the right cerebellar hemisphere, rTMS was administered at a fixed level of 55% of maximum stimulator output. Washout period of more than 13 days are set between each session. 1. right primary motor area, 2. right dorsal premotor area, 3. right ventral premotor area, 4. right cerebellar hemisphere, 5. right primary motor area (sham stimulation)
Interventions/Control_2	Repeated transcranial magnetic stimulation (rTMS) with intensity of 90% of resting motor threshold and 900 pulses for one session was given to the following brain regions in the following order at the low frequency (1 Hz). Regarding the right cerebellar hemisphere, rTMS was administered at a fixed level of 55% of maximum stimulator output. Washout period of more than 13 days are set between each session. 2. right dorsal premotor area, 3. right ventral premotor area, 1. right primary motor area, 5. right primary motor area (sham stimulation), 4. right cerebellar hemisphere
Interventions/Control_3	Repeated transcranial magnetic stimulation (rTMS) with intensity of 90% of resting motor threshold and 900 pulses for one session was given to the following brain regions in the following order at the low frequency (1 Hz). Regarding the right cerebellar hemisphere, rTMS was administered at a fixed level of 55% of maximum stimulator output. Washout period of more than 13 days are set between each session. 1. right primary motor area, 4. right cerebellar hemisphere, 5. right primary motor area (sham stimulation), 2. right dorsal premotor area, 3. right ventral premotor area,
Interventions/Control_4	Repeated transcranial magnetic stimulation (rTMS) with intensity of 90% of resting motor threshold and 900 pulses for one session was given to the following brain regions in the following order at the low frequency (1 Hz). Regarding the right cerebellar hemisphere, rTMS was administered at a fixed level of 55% of maximum stimulator output. Washout period of more than 13 days are set between each session. 3. right ventral premotor area, 2. right dorsal premotor area, 5. right primary motor area (sham stimulation), 1. right primary motor area, 4. right cerebellar hemisphere
Interventions/Control_5	Repeated transcranial magnetic stimulation (rTMS) with intensity of 90% of resting motor threshold and 900 pulses for one session was given to the following brain regions in the following order at the low frequency (1 Hz). Regarding the right cerebellar hemisphere, rTMS was administered at a fixed level of 55% of maximum stimulator output. Washout period of more than 13 days are set between each session. 2. right dorsal premotor area, 1. right primary motor area, 4. right cerebellar hemisphere, 5. right primary motor area (sham stimulation), 3. right ventral premotor area
Interventions/Control_6
Interventions/Control_7
Interventions/Control_8
Interventions/Control_9
Interventions/Control_10

Eligibility
Age-lower limit	10 years-old <=
Age-upper limit	15 years-old >=
Gender	Male
Key inclusion criteria	1. Boys who were diagnosed as autism spectrum disorder in the clinic of developmental disorders in Osaka University Hospital. The diagnosis was made by specialists in child neurology or psychiatry according to the DSM-V (The Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders), ADI-R (Autism Diagnostic Interview, Revised) which is a specific interview form to the parent with ASD, or AODS (Autism Diagnostic Observation Schedule) which is a specific observation tool for autism diagnosis. 2. Children in whom organic brain abnormality or epileptic abnormality were denied by MRI and EEG examination performed less than two and one year prior to rTMS, respectively. 3. Children with IQ more than 80. 4. Right-handed children judged by Edinburgh Handedness Inventory. 5. Children with age of 10 to 15 years when consent are obtained. Written informed consent should be obtained after the detailed explanation.
Key exclusion criteria	1. Those who suffer from physical comorbid disorders except developmental disorders. 2. Those who have any instrument including metal in the head except oral cavity. 3. Those who have a history of heart, gastrointestinal, chronic renal diseases, head trauma or brain tumors. 4. Those who were instrumented with a cardiac pacemaker, a deep brain or a spinal stimulation or drug-delivery pump. 5. Those who possess intracranial organic lesions and at increased risk for induction of convulsion. 6. Those who have a history of convulsive diseases including febrile seizures, epileptic seizures or epilepsy. 7. Those who take medicine that decrease the convulsive threshold such as anti-depressant, anti-psycotic or anti-histamine drugs. 8. Those who is judged to be not suitable for participating in the study by responsible or contributing doctors.
Target sample size	20

Research contact person
Name of lead principal investigator	Masako Taniike
Organization	Osaka University Hospital
Division name	Pediatrics
Address	2-2 Yamadaoka, Suita
TEL	06-6879-3863
Email	masako@kokoro.med.osaka-u.ac.jp

Public contact
Name of contact person	Kuriko Shimono
Organization	Osaka University Hospital
Division name	Pediatrics
Address	2-2 Yamadaoka, Suita
TEL	06-6879-3863
Homepage URL
Email	kuriko@ped.med.osaka-u.ac.jp

Sponsor
Institute	Osaka University
Institute
Department

Funding Source
Organization	Japan Science AND Technology Agency
Organization
Division
Category of Funding Organization	Japanese Governmental office
Nationality of Funding Organization

Other related organizations
Co-sponsor
Name of secondary funｄer(s)

Secondary IDs
Secondary IDs	NO
Study ID_1
Org. issuing International ID_1
Study ID_2
Org. issuing International ID_2
IND to MHLW

Institutions
Institutions

Other administrative information
Date of disclosure of the study information	2016 Year 11 Month 01 Day

Progress
Recruitment status	Enrolling by invitation
Date of protocol fixation	2016 Year 10 Month 01 Day
Anticipated trial start date	2017 Year 03 Month 01 Day
Last follow-up date
Date of closure to data entry
Date trial data considered complete
Date analysis concluded

Related information
URL releasing protocol
Publication of results	Unpublished
URL releasing results
Results
Other related information

Management information
Registered date	2016 Year 09 Month 29 Day
Last modified on	2018 Year 04 Month 10 Day

Link to view the page
URL(English)	https://upload.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000027849