Precision TMS Treatment Guided by Personalized Brain Functional Sectors (pBFS) for ASD

Study Overview
=================
Brief Summary
-----------------
This study will evaluate the efficacy and safety of pBFS-guided TMS treatment for social communication ability in autism spectrum disorder children, adolescents and young adults.

Detailed Description
-----------------
Autism spectrum disorder is a neurodevelopmental disorder characterized by impaired social communication and repetitive behaviors. Using the personalized Brain Functional Sectors (pBFS) technique, investigators could precisely identify individualized brain areas underlying social communication and executive function based on the resting-state functional MRI data. Two tailored TMS intervention targets will be selected for each participant by a blinded researcher. One is the dorsal medial prefrontal cortex (DMPFC) target within the social function network, and the other one is the dorsal lateral prefrontal cortex (DLPFC) target within the executive function network. 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. The two sham groups will be combined as one control group in later analyses. Each participant will receive 5 days of treatment per week for 8 weeks. Functional MRI data under sedation will be collected pre-and post-treatment.

Official Title
-----------------
Personalized Brain Functional Sectors (pBFS) Guided Transcranial Magnetic Stimulation (TMS) Treatment for Autism Spectrum Disorder (ASD): a Single-center, Sham-controlled, Double-blinded, Randomized Clinical Trial Study

Conditions
-----------------
Autism Spectrum Disorder

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 6-30 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
-----------------
Minimum Age: 6 Years
Maximum Age: 30 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 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>|
| 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>|
| 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>|
| 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>|

What is the study measuring?
-----------------
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
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
TMS, personalized medicine, ASD, fMRI