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Efficacy and Mechanism of Repetitive Transcranial Magnetic Stimulation in Children With Autism Spectrum Disorders

Primary Purpose

Autism Spectrum Disorder

Status
Recruiting
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
repeated transcranial magnetic stimulation (continuous theta-burst stimulation)
sham repeated transcranial magnetic stimulation
Sponsored by
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Autism Spectrum Disorder focused on measuring Repetitive Transcranial Magnetic Stimulation(rTMS), Autism Spectrum Disorder, Intervention, Social Deficits, Language Function, Children

Eligibility Criteria

4 Years - 10 Years (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Children aged 4-10 years old Meet the diagnostic criteria for ASD of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) ASD Diagnosis confirmed by the Autism Diagnostic Observation Schedule (ADOS) or Autism Diagnostic Interview, Revised (ADI-R) IQ of 50 or above Provide written informed consents Exclusion Criteria: With metal implants in the body History of epilepsy or other neurological disease Require surgical treatment due to structural abnormalities indicated by brain MRI Diagnosed with genetic and chromosomal abnormalities With psychiatric/mental disorder (e.g., very early-onset schizophrenia) other than ASD Suffer from serious heart disease and/or severe hearing impairment Intracranial hypertension Participating in other clinical trials Participants who received other interventions within 4 weeks prior to enrollment.

Sites / Locations

  • Henan Children's HospitalRecruiting
  • Qilu Hospital of Shandong UniversityRecruiting
  • Xinhua Hospital, Shanghai Jiao Tong University School of MedicineRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

Intervention Group

Sham Group

Arm Description

participants in intervention group will receive accelerated continuous theta-burst stimulation (a-cTBS) on the left primary motor cortex (M1) for 5 consecutive days.

The sham group will be stimulated with a pseudo-stimulation coil, which emitted sounds with the same intensity, rhythm and vibratory sensation as the real stimulation, and the intervention target, duration and frequency are the same as the real intervention group.

Outcomes

Primary Outcome Measures

Changes of Social Responsiveness Scale, Second Edition (SRS-2) scores from pre-intervention to post-intervention
SRS provides the multi-dimensional measure of social interaction allowing the rating of social impairment in ASD. SRS generates a total score and five theoretical subscale scores (labeled social awareness, social cognition, social communication, social motivation, restricted interests and repetitive behavior), and higher scores are indicative of greater social impairment.
Changes of Social Responsiveness Scale, Second Edition (SRS-2) scores from pre-intervention to 1 month follow-up
SRS provides the multi-dimensional measure of social interaction allowing the rating of social impairment in ASD. SRS generates a total score and five theoretical subscale scores (labeled social awareness, social cognition, social communication, social motivation, restricted interests and repetitive behavior), and higher scores are indicative of greater social impairment.

Secondary Outcome Measures

Chinese Communicative Development Inventory (CCDI)
a parent questionnaire serves as a powerful tool to evaluate the early vocabulary development and language skills of older children with developmental disorders and the effectiveness of their interventions. CCDI yields two subscale scores, including words produced score and sentence complexity score.Higher scores suggest better language level.
Language Comprehension Test
Peabody Picture Vocabulary Test (PPVT) is a standard assessment tool for measuring single-word comprehension, to objectively evaluate the language ability of the children involved in our study. Higher scores suggest better language level. Meanwhile, a sentence-picture matching test will be administered to test children's language comprehension abilities in the syntactic domain.
Multilingual Assessment Instrument for Narratives (MAIN)
assess narrative comprehension and production skills of children who exhibited a certain level of expressive ability (at least can use flexible phrases).In this test, children tell or retell the stories and answer some questions, with assessors evaluating performance across four dimensions: story structure, structural complexity, internal state terms, and comprehension questions. Higher scores suggest better language level.
Clinical Global Impression Scale (CGI)
we used CGI-I to rate how much the patient's illness has improved or worsened relative to a baseline measurement (a seven-point scale: 1 = "very much improved" to 7 = "very much worse")
Vineland Adaptive Behavior Scales, Third Edition (Vineland-3)
The Vineland Adaptive Behavior Scales were designed to address adaptive behavior, or the personal and social skills necessary for everyday independent living. For individuals with ASDs, the Vineland can be used for tracking and reporting progress of intervention or treatment. Domains of adaptive functioning assessed with the Vineland include: Communication, Daily Living Skills, Socialization, Motor Skills. The higher scores suggest better adaptive level.
Electroencephalography (EEG)
Electroencephalography (EEG): We plan to collect resting-state and task-related EEG data from children with ASD at baseline, after 5 days of intervention after intervention to evaluate changes in power spectrum and inter-trial phase coherence (ITPC) in the alpha and theta frequency bands at different time points. The EEG data will be collected using a 128-channel EEG system with a sampling rate of 1000 Hz and a reference electrode at Cz (central zero). Prior to data collection, we will ensure that the resistance of each channel is below 100 kΩ.

Full Information

First Posted
June 13, 2023
Last Updated
August 27, 2023
Sponsor
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Collaborators
Shanghai Mental Health Center, Zhengzhou Children's Hospital, China, Qilu Hospital of Shandong University
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1. Study Identification

Unique Protocol Identification Number
NCT05927792
Brief Title
Efficacy and Mechanism of Repetitive Transcranial Magnetic Stimulation in Children With Autism Spectrum Disorders
Official Title
Efficacy and Mechanism of Repetitive Transcranial Magnetic Stimulation in Children With Autism Spectrum Disorders: a Multicenter, Randomized Controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
July 17, 2023 (Actual)
Primary Completion Date
September 1, 2025 (Anticipated)
Study Completion Date
December 30, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
Collaborators
Shanghai Mental Health Center, Zhengzhou Children's Hospital, China, Qilu Hospital of Shandong University

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
This study is a prospective, two-center, randomized, single-blind controlled trial to enroll 200 children with autism spectrum disorders (ASD). The investigators hope to further explore the effectiveness of accelerated continuous theta-burst stimulation (a-cTBS) over the left primary motor cortex (M1) to improve core symptoms in ASD children based on a previous open-label clinical trial.
Detailed Description
This study is a prospective, two-center, randomized, single-blind controlled trial. Xinhua hospital and Henan children's hospital expect to enroll 200 children with autism spectrum disorders (ASD) in total. The children seen at Department of Developmental Behavioral Child Health, who meet the The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition(DSM-5) ASD diagnostic criteria and strict inclusion/exclusion criteria, can be enrolled for the intervention after informed consent. At each study center, participants will be randomized into intervention group and sham group stratified by IQ level. The participants, their legal guardians, and the assessors were unaware of the grouping except for the intervention operator (single-blind). During the trial, participants in intervention group will receive accelerated continuous theta-burst stimulation (a-cTBS) on the left primary motor cortex (M1) for 5 consecutive days. The sham group will be stimulated with a pseudo-stimulation coil, which emitted sounds with the same intensity, rhythm and vibratory sensation as the real stimulation, and the intervention target, duration and frequency are the same as the real intervention group. All participants need to 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 investigators hope to further explore the effectiveness of accelerated continuous theta-burst stimulation (a-cTBS) over the left primary motor cortex (M1) to improve core symptoms in ASD children based on a previous open-label clinical trial and investigate the appropriate intervention model, effective adaptation population and underlying neurological mechanisms.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Autism Spectrum Disorder
Keywords
Repetitive Transcranial Magnetic Stimulation(rTMS), Autism Spectrum Disorder, Intervention, Social Deficits, Language Function, Children

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantOutcomes Assessor
Masking Description
The participants, their legal guardians, and the assessors were unaware of the grouping except for the intervention operator (single-blind).
Allocation
Randomized
Enrollment
200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention Group
Arm Type
Experimental
Arm Description
participants in intervention group will receive accelerated continuous theta-burst stimulation (a-cTBS) on the left primary motor cortex (M1) for 5 consecutive days.
Arm Title
Sham Group
Arm Type
Sham Comparator
Arm Description
The sham group will be stimulated with a pseudo-stimulation coil, which emitted sounds with the same intensity, rhythm and vibratory sensation as the real stimulation, and the intervention target, duration and frequency are the same as the real intervention group.
Intervention Type
Device
Intervention Name(s)
repeated transcranial magnetic stimulation (continuous theta-burst stimulation)
Intervention Description
Participants in intervention group will receive cTBS over the left M1for 5 consecutive days. The detailed parameters as follows: 80% of resting motor threshold (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).
Intervention Type
Device
Intervention Name(s)
sham repeated transcranial magnetic stimulation
Intervention Description
The sham group will be stimulated with a pseudo-stimulation coil, which emitted sounds with the same intensity, rhythm and vibratory sensation as the real stimulation, and the intervention target, duration and frequency are the same as the real intervention group.
Primary Outcome Measure Information:
Title
Changes of Social Responsiveness Scale, Second Edition (SRS-2) scores from pre-intervention to post-intervention
Description
SRS provides the multi-dimensional measure of social interaction allowing the rating of social impairment in ASD. SRS generates a total score and five theoretical subscale scores (labeled social awareness, social cognition, social communication, social motivation, restricted interests and repetitive behavior), and higher scores are indicative of greater social impairment.
Time Frame
within 2 weeks before the intervention (pre-intervention), within 3 days after the completion of the intervention course (post-intervention)
Title
Changes of Social Responsiveness Scale, Second Edition (SRS-2) scores from pre-intervention to 1 month follow-up
Description
SRS provides the multi-dimensional measure of social interaction allowing the rating of social impairment in ASD. SRS generates a total score and five theoretical subscale scores (labeled social awareness, social cognition, social communication, social motivation, restricted interests and repetitive behavior), and higher scores are indicative of greater social impairment.
Time Frame
within 2 weeks before the intervention (pre-intervention), 1 month following the last intervention session (one month follow-up)
Secondary Outcome Measure Information:
Title
Chinese Communicative Development Inventory (CCDI)
Description
a parent questionnaire serves as a powerful tool to evaluate the early vocabulary development and language skills of older children with developmental disorders and the effectiveness of their interventions. CCDI yields two subscale scores, including words produced score and sentence complexity score.Higher scores suggest better language level.
Time Frame
within 2 weeks before the intervention (pre-intervention), 1 month following the last intervention session (one month follow-up)
Title
Language Comprehension Test
Description
Peabody Picture Vocabulary Test (PPVT) is a standard assessment tool for measuring single-word comprehension, to objectively evaluate the language ability of the children involved in our study. Higher scores suggest better language level. Meanwhile, a sentence-picture matching test will be administered to test children's language comprehension abilities in the syntactic domain.
Time Frame
within 2 weeks before the intervention (pre-intervention), 1 month following the last intervention session (one month follow-up)
Title
Multilingual Assessment Instrument for Narratives (MAIN)
Description
assess narrative comprehension and production skills of children who exhibited a certain level of expressive ability (at least can use flexible phrases).In this test, children tell or retell the stories and answer some questions, with assessors evaluating performance across four dimensions: story structure, structural complexity, internal state terms, and comprehension questions. Higher scores suggest better language level.
Time Frame
within 2 weeks before the intervention (pre-intervention), 1 month following the last intervention session (one month follow-up)
Title
Clinical Global Impression Scale (CGI)
Description
we used CGI-I to rate how much the patient's illness has improved or worsened relative to a baseline measurement (a seven-point scale: 1 = "very much improved" to 7 = "very much worse")
Time Frame
within 3 days after the completion of the intervention course (post-intervention), 1 month following the last intervention session (one month follow-up)
Title
Vineland Adaptive Behavior Scales, Third Edition (Vineland-3)
Description
The Vineland Adaptive Behavior Scales were designed to address adaptive behavior, or the personal and social skills necessary for everyday independent living. For individuals with ASDs, the Vineland can be used for tracking and reporting progress of intervention or treatment. Domains of adaptive functioning assessed with the Vineland include: Communication, Daily Living Skills, Socialization, Motor Skills. The higher scores suggest better adaptive level.
Time Frame
within 2 weeks before the intervention (pre-intervention), 1 month following the last intervention session (one month follow-up)
Title
Electroencephalography (EEG)
Description
Electroencephalography (EEG): We plan to collect resting-state and task-related EEG data from children with ASD at baseline, after 5 days of intervention after intervention to evaluate changes in power spectrum and inter-trial phase coherence (ITPC) in the alpha and theta frequency bands at different time points. The EEG data will be collected using a 128-channel EEG system with a sampling rate of 1000 Hz and a reference electrode at Cz (central zero). Prior to data collection, we will ensure that the resistance of each channel is below 100 kΩ.
Time Frame
within 2 weeks before the intervention (pre-intervention), within 2 days after the completion of the intervention course (post-intervention)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
4 Years
Maximum Age & Unit of Time
10 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Children aged 4-10 years old Meet the diagnostic criteria for ASD of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) ASD Diagnosis confirmed by the Autism Diagnostic Observation Schedule (ADOS) or Autism Diagnostic Interview, Revised (ADI-R) IQ of 50 or above Provide written informed consents Exclusion Criteria: With metal implants in the body History of epilepsy or other neurological disease Require surgical treatment due to structural abnormalities indicated by brain MRI Diagnosed with genetic and chromosomal abnormalities With psychiatric/mental disorder (e.g., very early-onset schizophrenia) other than ASD Suffer from serious heart disease and/or severe hearing impairment Intracranial hypertension Participating in other clinical trials Participants who received other interventions within 4 weeks prior to enrollment.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Fei Li, MD, PhD
Phone
+86-18930830950
Email
feili@shsmu.edu.cn
First Name & Middle Initial & Last Name or Official Title & Degree
Hangyu Tan, MD
Phone
+86-18002304570
Email
astro4570no1@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Fei Li, MD, PhD
Organizational Affiliation
Shanghai Jiaotong University School of Medicine Xinhua Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Henan Children's Hospital
City
Zhengzhou
State/Province
Henan
ZIP/Postal Code
450000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shuanfeng Fang, Doctor
Phone
13937193903
Email
fangshuanfeng@126.com
Facility Name
Qilu Hospital of Shandong University
City
Qilu
State/Province
Shandong
ZIP/Postal Code
250000
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Aihua Cao, Doctor
Phone
18560086317
Email
xinercah@163.com
Facility Name
Xinhua Hospital, Shanghai Jiao Tong University School of Medicine
City
Shanghai
State/Province
Shanghai
ZIP/Postal Code
200092
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Fei Li, Doctor
Phone
18930830950
Email
feili@shsmu.edu.cn

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
Study Protocol, Statistical Analysis Plan, Informed Consent Form (ICF), etc are available through contacting researchers if required.

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Efficacy and Mechanism of Repetitive Transcranial Magnetic Stimulation in Children With Autism Spectrum Disorders

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