pBFS-guided Noninvasive Neuromodulation for Pre-school Children With ASD

Study Overview
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Brief Summary
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This randomized controlled trial aims to evaluate the efficacy and safeness of the pBFS-guided rTMS intervention for core symptom relief in pre-school children with autism spectrum disorder (ASD).

Detailed Description
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Autism spectrum disorder is a neurodevelopmental disorder, begins early in life. Using the personalized brain functional sectors (pBFS) technology, investigators could precisely identify individualized brain function networks based on the functional MRI scan. For each participant, two personalised TMS intervention targets will be chosen by blinded researcher. One executive function network target is located in the dorsal lateral prefrontal cortex (DLPFC) , and the other social function network target is located in the dorsal medial prefrontal cortex (DMPFC). The participants will be equally randomized to the following four groups, active iTBS to the left DMPFC or the left DLPFC, and sham iTBS to either the left DMPFC or left DLPFC at a ratio of 2:2:1:1. Later analyses will combine the two sham groups as one control group. Each participant will receive 1800 pulse active or sham iTBS (100% RMT) in each session, 3 sessions daily, 5 days per week for 8 weeks, as well as background behavioral training between iTBS sessions. Pre-and post-treatment functional MRI data will be collected under sedation.

Official Title
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Personalized Brain Functional Sectors (pBFS) Guided Noninvasive Neuromodulation Treatment for Pre-school Children With Autism Spectrum Disorder (ASD): a Single-center, Double-blinded, Sham-Controlled, Randomized Clinical Trial Study

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Device: active iTBS
* Device: active iTBS
* Device: sham iTBS
* Device: sham iTBS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 2.5-6 years old Have the diagnosis of autism spectrum disorder ADOS-2 score is higher than the ASD cut-offs Capacity to follow the study procedures, including fMRI scan under sedation, assessment, and rehabilitation training Participant's parents or other legal guardians give informed consent Exclusion Criteria: Current or history of psychotic disorders, such as schizophrenia, schizoaffective disorder, bipolar disorder Severe self-injury or suicidal behavior presented in the last 1 year Severe visual, auditory, or motor disability that interferes with any study procedure Current, history or family history of epilepsy Known severe physical diseases, such as congenital heart defect, traumatic brain injury Metal implantations, which are contradicted by MRI or TMS, such as artificial cardiac pacemakers, stents, cochlear implants Received TMS, tCS, FUS, or other neuromodulation treatment in the last 3 months Currently participating in other clinical trials

Ages Eligible for Study
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Minimum Age: 30 Months
Maximum Age: 6 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DLPFC group<br>Active iTBS will be delivered to the left DLPFC. | Device: active iTBS<br>* Each participant will receive 1800 pulse active iTBS (100% RMT) in each session, 3 sessions per day, 5 days per week for 8 weeks.<br>|
| Experimental: DMPFC group<br>Active iTBS will be delivered to the left DMPFC. | Device: active iTBS<br>* Each participant will receive 1800 pulse active iTBS (100% RMT) in each session, 3 sessions per day, 5 days per week for 8 weeks.<br>|
| Sham Comparator: Sham to DLPFC group<br>Sham iTBS will be delivered to the left DLPFC. | Device: sham iTBS<br>* Each participant will receive 1800 pulse sham iTBS (100% RMT) in each session, 3 sessions per day, 5 days per week for 8 weeks.<br>|
| Sham Comparator: Sham to DMPFC group<br>Sham iTBS will be delivered to the left DMPFC. | Device: sham iTBS<br>* Each participant will receive 1800 pulse sham iTBS (100% RMT) in each session, 3 sessions per day, 5 days per week for 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADOS-2 SA change | The social affect (SA) dimension score change of autism diagnostic observation scale, 2nd edition (ADOS-2) from baseline. Higher scores mean a worse outcome. | Pre-treatment (baseline), immediately post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ADOS-2 total score change | The total score change of autism diagnostic observation scale, 2nd edition (ADOS-2) from baseline. Higher scores mean a worse outcome. | Pre-treatment (baseline), immediately post-treatment | 
| CBCL score change | Score change of the child behavior checklist (CBCL) from baseline. Higher scores mean a worse outcome. | Pre-treatment (baseline), immediately post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TMS, ASD, fMRI, personalized medicine