The Therapeutic Effects of Continuous Theta Burst Stimulation in Autism Spectrum Disorder

Study Overview
=================
Brief Summary
-----------------
The investigator would like to investigate the impact of theta burst stimulation over left dorsolateral prefrontal cortex in autism spectrum disorder

Official Title
-----------------
To Explore the Therapeutic Effects of Continuous Theta-burst Stimulation Over Left Dorsolateral Prefrontal Cortex in Autism Spectrum Disorder

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

Intervention / Treatment
-----------------
* Device: continuous theta burst stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: autism spectrum disorder, confirmed by ADOS Exclusion Criteria: current and past systemic disease current and past major psychiatric disorders including schizophrenia, bipolar affective disorder and major depressive disorder current and past brain injuries intelligence < 70 seizure history pregnant

Ages Eligible for Study
-----------------
Minimum Age: 8 Years
Maximum Age: 30 Years

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

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active<br>Participants received the real intervention of TBS (cTBS 600) over the left dorsolateral prefrontal cortex for 8 weeks (2 days/week). *cTBS = continuous theta burst stimulation | Device: continuous theta burst stimulation<br>* stimulatory protocol<br>|
| Sham Comparator: Sham<br>Participants received the sham intervention of TBS (coil tilted one-wing 90° off the head) over the left dorsolateral prefrontal cortex for 8 weeks (2 days/week). | Device: continuous theta burst stimulation<br>* stimulatory protocol<br>|
| No Intervention: Normal control<br>No intervention. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of total scores of Social Responsiveness Scale | Social Responsiveness Scale can measure the autism clinical severity with the range from 65-260. The lower scores stand for better social responsiveness. | baseline; post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | 
| Changes of total scores of Repetitive Behavior Scale-Revised | Repetitive Behavior Scale-Revised is a questionnaire that focuses on repetitive behavior. The score ranges from 0-129. The lower scores stand for lower repetitive behavior. | baseline; post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of total scores of Emotional Dysregulation Inventory | Emotional Dysregulation Inventory is a parents' report questionnaire for emotional dysregulation. The score ranges from 0-120. The lower scores stand for better emotional regulation. | baseline; post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | 
| Changes of total scores of Adaptive Behavior Assessment System | Adaptive Behavior Assessment System is a parents' report questionnaire for adaptive behavior. The score ranges from 9-171. The higher scores stand for better adaptive behavior. | baseline; post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | 
| Changes of total scores of Vineland Adaptive Behavior Scales | Vineland Adaptive Behavior Scales is a parents' report questionnaire for adaptive behavior. The score ranges from 0-484. The higher scores stand for better adaptive behavior. | baseline; post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | 
| Changes in accuracy of Frith-Happe animation | A quick and objective test of Theory of Mind. 8 questions in total, the more correct questions stand for better Social Cognition. | baseline; post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | 
| Changes in accuracy of Eyes task | An advanced test for Theory of Mind. 43 questions in total, the more correct questions stand for better social skills. | baseline; post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | 
| Changes in accuracy of Wisconsin Card Sorting Test | An advanced test for cognitive flexibility. 128 questions in total, the more correct questions stand for better cognitive flexibility. | baseline; post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | 
| Changes of total scores of Behavior Rating Inventory of Executive Function | Behavior Rating Inventory of Executive Function is a parents' report questionnaire for executive function. The score ranges from 86-258. The lower scores stand for better executive function. | baseline; post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | 
| Raven's Progressive Matrices | An advanced test for for executive function. 60 questions in total, the more correct questions stand for better executive function. | baseline; post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | 
| Autism Diagnostic Observation Schedule - Generic | The Autism Diagnostic Observation Schedule is a semi-structured assessment of communication, social interaction, and play (or imaginative use of materials) for individuals suspected of having autism spectrum disorders. The social affect domain includes the social and communication items ranging from 0 to 20. The higher scores stand for more clinical severity of autism spectrum disorder. | baseline; post TBS (8 weeks after baseline) | 
| MRI T1 | Brain structural volumes (cm²) | baseline; post TBS (8 weeks after baseline) | 
| functional MRI (resting-state/biological motion task) - BOLD signal | Blood-oxygen-level-dependent (BOLD) signal is a measurement used in fMRI, which reflects the neural activity. | baseline; post TBS (8 weeks after baseline) | 
| Diffusion Tensor Imaging (DTI) - FA | Fractional anisotropy (FA) is a measurement used in DTI, which reflects the movement of water molecules. FA ranges from 0 to 1, the higher FA value may represent more intact axons. | baseline; post TBS (8 weeks after baseline) |