Efficacy and Mechanism of rTMS in Children With ASD: an Open-label Clinical Trial(Ⅱ)

Study Overview
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Brief Summary
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This study is a open-label clinical trial involving over 30 children aged ≥4 years with autism spectrum disorder. During the study, subjects received repeated transcranial magnetic stimulation (rTMS) intervention at the left primary motor cortex (M1) 10 times per day for 5 days. From the beginning of intervention to the end of 4 weeks after the completion of intervention, the subjects's clinical symptomatology, cognitive psychology, neuroimaging, and adverse events will be followed up. Based on results from a recent unpublished pilot data, the investigators propose that cTBS treatment will induce a significant improvement in verbal/social communication performance in ASD children.

Detailed Description
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Participants will receive continuous theta burst stimulation (cTBS) for a 5 day period (5 sessions), 10 times a day, for about 3min each. If feasible for the participant, all stimulation sessions will be held at the same time of the day. During this study, participants' clinical symptomatology, cognitive psychology, neuroimaging, and adverse events will be followed up for three times, specifically before intervention, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention.The purpose of this current study is to explore whether rTMS can improve the clinical symptoms of children with autism spectrum disorder in China, and to explore the neurophysiological mechanism of rTMS for autistic children.

Official Title
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Efficacy and Mechanism of Repeated Transcranial Magnetic Stimulation in Children With Autism Spectrum Disorder: an Open-label Clinical Trial(Ⅱ)

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Device: repetitive Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children aged ≥4 years. Meeting the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders, Edition 5 (DSM-5) . Confirmed by the ADOS and/or ADI-R diagnostic tool. Informed consent. Exclusion Criteria: Patients with metal implants . Patients with neurological diseases such as epilepsy . Patients requiring surgical treatment due to structural abnormalities indicated by brain MRI . Genetic or chromosomal abnormalities . Suffering from mental disorders (such as mood disorders, etc.) Suffering from serious heart disease . Hearing-impaired . Intracranial hypertension . Participating in other clinical trials. Participants who received other interventions within 4 weeks prior to enrollment.

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rTMS Group<br>Participants will receive continuous theta burst stimulation (cTBS) for a 5-day period (5 sessions), at an intensity that is 80% of the resting motor threshold (RMT) . cTBS repeats ten times a day with about 50 min interval . If feasible for the participant, all stimulation sessions will be held at the same time of the day. Treatment will be applied in left primary motor cortext (M1). | Device: repetitive Transcranial Magnetic Stimulation<br>* A technique that involves the use of electrical coils on the head to generate a brief magnetic field which reaches the cerebral cortex.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Social Response Scale (SRS) | SRS is a questionnaire used to assess the presence and severity of social impairment, with high scores indicating severe symptoms. Change of the SRS from baseline to 1 month after treatment to evaluate the effect of rTMS treatment on ASD children. | Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Childhood Autism Rating Scale (CARS) | CARS is a behaviour-rating scale used to assess the presence and severity of the symptoms of autism spectrum disorder(ASD), with scores ranging from 15 to 60 and high scores indicating severe symptoms. Change of the CARS from baseline to 1 months after treatment to evaluate the effect of rTMS treatment on ASD. children. | Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention. | 
| Behavior Rating Inventory of Executive Function(BRIEF) | Specifically the investigators will evaluate the changes in executive function (EF) scores before and after cTBS treatment. The higer scores indicate more impairment in executive function. | Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention. | 
| Conners Scale | Conners is a questionnaire that asks about things like behavior, work or schoolwork, and social life. The answers show ADHD symptoms and how serious they are. There，parents fill out scales for children. | Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention. | 
| Repetitive Stereotyped Behavior - Revised (RBS-R) | The Repetitive Behaviors Scale - Revised (RBS-R) is a questionnaire that is used to measure the breadth of repetitive behavior in children, adolescents, and adults with Autism Spectrum disorders. The RBS-R provides a quantitative, continuous measure of the full spectrum of repetitive behaviors. The RBS-R consists of six subscales including: Stereotyped Behavior, Self-injurious Behavior, Compulsive Behavior, Routine Behavior, Sameness Behavior, and Restricted Behavior, that have no overlap of item content. | Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention. | 
| Peabody Picture Vocabulary Test（PPVT） | The Peabody Picture Vocabulary Test is one of the most commonly used assessment tests that measure verbal ability. Change of the score from baseline to 1 months after treatment to evaluate the effect of rTMS treatment on ASD children's verbal ability. | Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention. | 
| Chinese Communicative Development Inventory (CCDI) | CCDI provides a powerful tool to assess early vocabulary development ，and it is a reliable predictor of children's later language skills. Change of the score from baseline to 1 months after treatment to evaluate the effect of rTMS treatment on ASD children's language. | Baseline and 4 weeks after the completion of intervention. | 
| Clinical Efficacy Rating Scale (CGI) | CGI is a scale used to assess the severity of the illness and the global improvement of the patient under intervention. | After the completion of 5-days intervention and 4 weeks after the completion of intervention. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Repetitive Transcranial Magnetic Stimulation（rTMS）, Continuous theta Burst Stimulation （cTBS）