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| Name | Class |
|---|---|
| Shanghai Mental Health Center | OTHER |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| rTMS Group | Experimental | 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| repetitive Transcranial Magnetic Stimulation | Device | A technique that involves the use of electrical coils on the head to generate a brief magnetic field which reaches the cerebral cortex. |
| 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. |
| 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. |
| 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) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Fei Li | Xinhua hospital Affilated to Shanghai Jiao Tong University School of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Fei Li | Shanghai | Shanghai Municipality | 200092 | China |
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| ID | Title | Description |
|---|---|---|
| FG000 | rTMS Group | Participants will receive accelerated continuous theta burst stimulation (a-cTBS, i.e. triplet standard cTBS, 1800 pulses/120s) for a 5 consecutive days, at an intensity that is 80% of the resting motor threshold (RMT) . a-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). 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | rTMS Group | Participants will receive accelerated continuous theta burst stimulation (a-cTBS, i.e. triplet standard cTBS, 1800 pulses/120s) for a 5 consecutive days, at an intensity that is 80% of the resting motor threshold (RMT) . a-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). |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention. |
|
A semi-structured interview was administered following each treatment session and 1 month follow-up.
rating the event as mild (no impairment, no need stopping trial), moderate (some impairment, need stopping trial, no need for intervention), severe (evidence of impairment, need stopping trial and need for intervention).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | rTMS Group | Participants will receive accelerated continuous theta burst stimulation (a-cTBS, i.e. triplet standard cTBS, 1800 pulses/120s) for a 5 consecutive days, at an intensity that is 80% of the resting motor threshold (RMT) . a-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). 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| agitation | Nervous system disorders | Non-systematic Assessment | during intervention period, mild and disappeared without any specific therapy. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Fei Li | Shanghai Jiaotong University School of Medicine Xinhua Hospital | 18930830950 | feili@shsmu.edu.cn |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 2, 2022 | May 23, 2023 | Prot_SAP_000.pdf |
| ICF | No | No | Yes | Informed Consent Form | Jun 21, 2022 | May 23, 2023 | ICF_001.pdf |
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| ID | Term |
|---|---|
| D000067877 | Autism Spectrum Disorder |
| ID | Term |
|---|---|
| D002659 | Child Development Disorders, Pervasive |
| D065886 | Neurodevelopmental Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
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| 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. |
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. |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Full Scale intelligence quotient (FSIQ) | We use the Wechsler Intelligence Scale to measure the intellectual ability of children. It can generate the full scale intelligence quotient (FSIQ) about children's the overall level of intelligence. The FSIQ ranges from 40-160, the higher values represent a better outcome. | Mean | Standard Deviation | units on a scale |
|
| Childhood Autism Rating Scale (CARS) | Childhood Autism Rating Scale (CARS) is one of the recommended diagnostic tools for ASD. It is comprised of 15 items (with a 4-point rating) covering a range of functions including social, emotional, adaptive, communicative, and cognitive. The CARS total score ranges from 15 to 60, a higher values represent a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| Autism Diagnostic Observation Schedule (ADOS) | The Autism Diagnostic Observation Schedule (ADOS) is a standardized diagnostic test for assessing autism spectrum disorder. ADOS determined social, communication, and social-communication domains scores, here we use the social-communication domain score as the ADOS score(social score and communication score are summed to compute). ADOS score ranges from 0-20, a higher values represent a worse outcome. | Mean | Standard Deviation | units on a scale |
|
| rTMS Group |
Participants will receive accelerated continuous theta burst stimulation (a-cTBS, i.e. triplet standard cTBS, 1800 pulses/120s) for a 5 consecutive days, at an intensity that is 80% of the resting motor threshold (RMT) . a-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). 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. |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline, and 4 weeks after the completion of intervention. |
|
|
|
| Secondary | 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. | Three parents of participants did not complete the questionnaire | Posted | Mean | Standard Deviation | score on a scale | Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention. |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention. |
|
|
|
| Secondary | 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. | Three subjects did not cooperate with the test, so their data were excluded from the analysis | Posted | Mean | Standard Deviation | score on a scale | Baseline, and 4 weeks after the completion of intervention. |
|
|
|
| Secondary | 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. | 8 subjects whose parents did not complete the follow-up scale or who had reached the highest measurable score on the scale in terms of ability (ceiling effect) were not included in the analysis | Posted | Mean | Inter-Quartile Range | score on a scale | Baseline and 4 weeks after the completion of intervention. |
|
|
|
| Secondary | 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). | Posted | Count of Participants | Participants | After the completion of 5-days intervention and 4 weeks after the completion of intervention. |
|
|
|
| Secondary | 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. | Posted | Median | Inter-Quartile Range | score on a scale | baseline, immediately after the completion of 5-days intervention, and 4 weeks after the completion of intervention. |
|
|
|
| Other Pre-specified | 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. | We successfully collected EEG data from 26 children before and after the intervention, and one patient was excluded after a quality control procedure. Due to limited implementation conditions (e.g., epidemics, installations) , we did not collect EEG data at 1-month follow-up. The phase locking value(PLV) and coherence (Coh) were not analyzed due to data and analyst issues. | Posted | Mean | Standard Deviation | W/Hz | Baseline, immediately after the completion of 5-days intervention. |
|
|
|
| Other Pre-specified | 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. | 14 children having certain expression ability to complete MAIN test. | Posted | Mean | Standard Deviation | score on a scale | Baseline, and 4 weeks after the completion of intervention. |
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| 0 |
| 30 |
| 0 |
| 30 |
| 8 |
| 30 |
|
| scalp pain | Skin and subcutaneous tissue disorders | Non-systematic Assessment | during the first few stimulation treatments, mild and disappeared without any specific therapy. |
|
| nausea | Nervous system disorders | Non-systematic Assessment | Occurred once during the follow-up period after full-doses treatment, disappeared without any specific therapy. |
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| 1month follow-up |
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| Title | Measurements |
|---|---|
|
|
|
| Telling_Structural Complexity_1month follow-up |
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| Telling_Internal States Terms_Pre-intervention |
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| Telling_Internal States Terms_1month follow-up |
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| Telling_Comprehension Questions_Pre-intervention |
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| Telling_Comprehension Questions_1month follow-up |
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| Retelling_Story Structure_Pre-intervention |
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| Retelling_Story Structure_1month follow-up |
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| Retelling_Structural Complexity_Pre-intervention |
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| Retelling_Structural Complexity_1month follow-up |
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| Retelling_Internal States Terms_Pre-intervention |
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| Retelling_Internal States Terms_1month follow-up |
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| Retelling_Comprehension Questions_Pre-intervention |
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| Retelling_Comprehension Questions_1month follow-up |
|