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

Not Applicable

Completed

Conditions: Autism Spectrum Disorder

Interventions: Device: repetitive Transcranial Magnetic Stimulation

Registration Number: NCT05472870

Lead Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Brief Summary: This study is a open-label clinical trial involving over 30 ASD children aged ≥4 years old. During the study, subjects received repeated transcranial magnetic stimulation (rTMS) intervention on the left primary motor cortex (M1) 10 times per day for 5 consecutive days and complete clinical assessments from pre-intervention to post-intervention. This study hopes to explore whether accelerated continuous theta-burst stimulation (a-cTBS) over left primary motor cortex (M1) can improve clinical symptoms of children with ASD in China.

Detailed Description: This study is a single-arm open-label clinical trial, designed to enroll at least 30 children with ASD aged over 4 years old.

During the trial, participants will receive accelerated continuous theta-burst stimulation (a-cTBS)on the left primary motor cortex (M1) for 5 consecutive days and complete clinical assessments within 2 weeks before the cTBS intervention (pre-cTBS), repeated within 3 days after the completion of the cTBS course (post-cTBS) and 1 month following the last cTBS session (one month follow-up), respectively. 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 investigate the neurophysiological mechanism of rTMS for ASD children.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 30

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
rTMS Group	repetitive Transcranial Magnetic Stimulation	Participants will receive cTBS over the left primary motor cortext (M1) for 5 consecutive days. The detailed parameters as follows: 80% of RMT, 60 cycles of 10 bursts of three pulses at 50 Hz were delivered in 2-second trains (5 Hz) with no intertrain interval (i.e. triplet standard cTBS, 1800 pulses, 120s). Stimulation sessions were delivered hourly, 10 sessions were applied per day (18,000 pulses/day).

Primary Outcome Measures

Name	Time	Method
Social Response Scale (SRS) Scores	Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention.	Social Response Scale (SRS) is a parent questionnaire used to assess the presence and severity of social impairment. The SRS generates a total score and five subscale scores (social awareness, social cognition, social communication, social motivation, and autistic mannerisms), and 5 subscales scores are summed to compute the total score; higher scores indicate greater social impairment. The SRS total score range is "0-195", the social awareness subscale score range is "0-24", the social cognition subscale score range is "0-36", the social communication subscale score range is "0-66", the social motivation subscale score range is "0-33", and the autistic mannerisms subscale score range is "0-36". We collected the SRS from baseline to 1 month follow-up to evaluate the effect of rTMS treatment on ASD syptoms among these children.

Secondary Outcome Measures

Name	Time	Method
Childhood Autism Rating Scale (CARS)	Baseline, and 4 weeks after the completion of intervention.	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.
Chinese Communicative Development Inventory (CCDI)	Baseline and 4 weeks after the completion of intervention.	CCDI provides a powerful tool to assess early vocabulary development and the language skills of older children with developmental disorders and the effectiveness of their intervention. Here we collected the CCDI words produced score, it ranges from 0-798. The higher scores mean a better outcome.
Behavior Rating Inventory of Executive Function (BRIEF)	Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention.	BRIEF is a quick and efficient measure of executive function(have school-age version (BRIEF-S) and preschool version (BRIEF-P)), we asked parents to complete the 86-item (BRIEF-S) or 63-item (BRIEF-P) form to rate a child's executive functions (1-3 score) within the context of his everyday environments (home or school). Here we report the BRIEF composite score, BRIEF-S score range is 86 -258 and BRIEF-P score range is 63-189. The higer scores indicate more impairment in executive function. We evaluate the changes in executive function (EF) scores before and after cTBS treatment.
Conners Parent Symptom Questionnaire (PSQ)	Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention.	Conners Parent Symptom Questionnaire (PSQ) is a questionnaire screening for children's behavioral problems (especially with ADHD), it has 48 items（4-stage: 0-3) that can be divided into 6 factors (conduct problems, learning problems, psychosomatic problems, impulsive-hyperactivity, anxiety, and hyperactivity index). Add the scores and divide by the item numbers of each factor to get Z score. Here we mainly observe the changes in Hyperactivity Index (HI) Z scores, it ranges from 0-3, a higher score mean a worse outcome.
Clinical Global Impression of Improvement (CGI-I)	After the completion of 5-days intervention and 4 weeks after the completion of intervention.	CGI is a scale used to assess the severity of the illness and the global improvement of the patient under intervention. Here we used Clinical Global Impression of Improvement (CGI-I) to rate how much the patient's illness has improved or worsened relative to baseline (a seven-point scale: 1 = "very much improved" to 7 = "very much worse"). The CGI was carried out by trained clinical assessors according to children's CARS、ADOS assessment results and parent interviews before and after intervention. We calculated the number of subjects with improvement (CGI-I≤3).
Repetitive Behaviors Scale - Revised (RBS-R)	baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention.	The Repetitive Behaviors Scale - Revised (RBS-R) is a 44-item (rated 0-3) 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. Here we use the RBS-R total score, it ranges from 0-132, the higher score means worse repetitive behavior.
Peabody Picture Vocabulary Test（PPVT）	Baseline, and 4 weeks after the completion of intervention.	The Peabody Picture Vocabulary Test is one of the most commonly used assessment tests for measuring single-word comprehension. The raw score ranges from 0-110, the higher scores mean a better outcome. we collected the PPVT raw score from baseline to 1 months after treatment to evaluate the effect of rTMS treatment on ASD children's words comprehension.