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

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

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.

Study Overview

• Status: Completed
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Device: repetitive Transcranial Magnetic Stimulation

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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 200092
      • Fei Li

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 12 years (Child)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: rTMS Group; 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).

Device: repetitive Transcranial Magnetic Stimulation; A technique that involves the use of electrical coils on the head to generate a brief magnetic field which reaches the cerebral cortex.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Social Response Scale (SRS) Scores	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.	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, and 4 weeks after the completion of intervention.
Behavior Rating Inventory of Executive Function (BRIEF)	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.	Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention.
Conners Parent Symptom Questionnaire (PSQ)	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.	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 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.	Baseline, and 4 weeks after the completion of intervention.
Chinese Communicative Development Inventory (CCDI)	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.	Baseline and 4 weeks after the completion of intervention.
Clinical Global Impression of Improvement (CGI-I)	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).	After the completion of 5-days intervention and 4 weeks after the completion of intervention.
Repetitive Behaviors Scale - Revised (RBS-R)	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.	baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Power Spectral Density (PSD) Within the Alpha Frequency Band	For EEG data, we caculated the power spectral density (PSD) within the alpha frequency band (8-13 Hz) for all channels.	Baseline, immediately after the completion of 5-days intervention.
Multilingual Assessment Instrument for Narratives (MAIN)	For a subset of ASD children with adequate expressive ability (those able to at least use phrases), we use Multilingual Assessment Instrument for Narratives (MAIN) tool to assess their narrative comprehension and production skills. In this test, children were asked to tell and retell the story and answer comprehension questions, and then assessors scored children's performance from four dimensions (i.e., story structure, structural complexity, and internal state terms and comprehension questions). The story structure score range is 0-18, structural complexity score range is 0-4, internal state terms score range is 0-no limit, and comprehension questions score range is 0-10. The higher score means better performance.	Baseline, and 4 weeks after the completion of intervention.

Collaborators and Investigators

• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
• Collaborators: Shanghai Mental Health Center
• Investigators: Principal Investigator: Fei Li, Xinhua hospital Affilated to Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): July 12, 2022
• Primary Completion (Actual): December 15, 2022
• Study Completion (Actual): January 20, 2023

Study Registration Dates

• First Submitted: July 22, 2022
• First Submitted That Met QC Criteria: July 22, 2022
• First Posted (Actual): July 25, 2022

Study Record Updates

• Last Update Posted (Actual): August 21, 2024
• Last Update Submitted That Met QC Criteria: August 15, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Repetitive Transcranial Magnetic Stimulation（rTMS）; Continuous theta Burst Stimulation （cTBS）
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder
• Other Study ID Numbers: XHEC-C-2022-008-4

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No