Autism Spectrum Disorder
Conditions
Brief summary
The investigator would like to investigate the impact of theta-burst stimulation over posterior superior temporal sulcus in children and adolescents with autism spectrum disorder
Interventions
DEVICEintermittent theta burst stimulation
stimulatory protocol
Sponsors
Chang Gung Memorial Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
7 Years to 18 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes of Total Scores of Social Responsiveness Scale | baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | Social Responsiveness Scale can measure the autism clinical severity with the range from 65-260. The lower scores stand for better social responsiveness. |
| Changes of Total Scores of Repetitive Behavior Scale-Revised | baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | RBS-R is a questionnaire that focuses on repetitive behavior. The score range from 0-129. The lower scores stand for lower repetitive behavior. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Functional MRI (Biological Motion Task) | baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline) | The MRI data have to be pre-processed before analysis. It may take few years. |
| Changes in Accuracy of Frith-Happe Animation | baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | A quick and objective test of Theory of Mind. 8 questions in total, the more correct questions stand for better Social Cognition (The score ranges from 0-48). |
| Diffusion Tensor Imaging | baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline) | The MRI data have to be pre-processed before analysis. It may take few years. |
| Resting State fMRI | baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline) | The MRI data have to be pre-processed before analysis. It may take few years. |
| Changes in Accuracy of Eyes Task | baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS) | An advanced test for Theory of Mind. 43 questions in total, the more correct questions stand for better social skills (The score ranges from 0-43). |
Countries
Taiwan
Participant flow
Pre-assignment details
Of the total 80 patients, 5 withdrew from the study.
Participants by arm
| Arm | Count |
|---|---|
| Active-Active Participants received the real intervention of TBS (iTBS 1200) over the posterior superior temporal sulcus for 8 weeks (2 days/week).
\*iTBS = intermittent theta burst stimulation | 40 |
| Sham-Active Participants received the sham intervention of TBS (coil tilted one-wing 90° off the head) over the posterior superior temporal sulcus for 4 weeks (2 days/week) and then received the real intervention of TBS (iTBS 1200) over the posterior superior temporal sulcus for 4 weeks (2 days/week).
\*iTBS = intermittent theta burst stimulation | 35 |
| Total | 75 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Physician Decision | 0 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 3 |
Baseline characteristics
| Characteristic | Sham-Active | Total | Active-Active |
|---|---|---|---|
| Age, Continuous | 12.5 years STANDARD_DEVIATION 2.9 | 12.8 years STANDARD_DEVIATION 2.9 | 13 years STANDARD_DEVIATION 2.8 |
| Comorbidity with ADHD | 14 Participants | 36 Participants | 22 Participants |
| Eye task | 24.8 units on a scale STANDARD_DEVIATION 6.9 | 22.7 units on a scale STANDARD_DEVIATION 7.8 | 20.8 units on a scale STANDARD_DEVIATION 8 |
| Frith-Happe Animation (Total) | 5.6 units on a scale STANDARD_DEVIATION 1.9 | 5.5 units on a scale STANDARD_DEVIATION 2 | 5.5 units on a scale STANDARD_DEVIATION 2.1 |
| Full scale intelligence | 90 units on a scale STANDARD_DEVIATION 14.7 | 89 units on a scale STANDARD_DEVIATION 15.8 | 88.2 units on a scale STANDARD_DEVIATION 16.7 |
| Medication (Antipsychotics) | 5 Participants | 10 Participants | 5 Participants |
| Medication (Atomoxetine) | 1 Participants | 2 Participants | 1 Participants |
| Medication (Methylphenidate) | 10 Participants | 24 Participants | 14 Participants |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Repetitive Behavior Scale-Revised | 33.5 units on a scale STANDARD_DEVIATION 20.6 | 32.8 units on a scale STANDARD_DEVIATION 19.7 | 32.2 units on a scale STANDARD_DEVIATION 18.9 |
| Sex: Female, Male Female | 5 Participants | 10 Participants | 5 Participants |
| Sex: Female, Male Male | 30 Participants | 65 Participants | 35 Participants |
| Social Responsiveness Scale | 102.1 units on a scale STANDARD_DEVIATION 23.2 | 104.9 units on a scale STANDARD_DEVIATION 23.8 | 107.3 units on a scale STANDARD_DEVIATION 24 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 40 | 0 / 35 |
| other Total, other adverse events | 4 / 40 | 10 / 35 |
| serious Total, serious adverse events | 0 / 40 | 0 / 35 |
Outcome results
Primary
Changes of Total Scores of Repetitive Behavior Scale-Revised
RBS-R is a questionnaire that focuses on repetitive behavior. The score range from 0-129. The lower scores stand for lower repetitive behavior.
Time frame: baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active-Active | Changes of Total Scores of Repetitive Behavior Scale-Revised | Baseline | 32.2 score on a scale | Standard Deviation 18.9 |
| Active-Active | Changes of Total Scores of Repetitive Behavior Scale-Revised | During TBS | 28.9 score on a scale | Standard Deviation 20.1 |
| Active-Active | Changes of Total Scores of Repetitive Behavior Scale-Revised | Post TBS | 25.9 score on a scale | Standard Deviation 20.5 |
| Active-Active | Changes of Total Scores of Repetitive Behavior Scale-Revised | One month follow up | 24.3 score on a scale | Standard Deviation 17.6 |
| Sham-Active | Changes of Total Scores of Repetitive Behavior Scale-Revised | One month follow up | 29 score on a scale | Standard Deviation 23.9 |
| Sham-Active | Changes of Total Scores of Repetitive Behavior Scale-Revised | Baseline | 33.5 score on a scale | Standard Deviation 20.6 |
| Sham-Active | Changes of Total Scores of Repetitive Behavior Scale-Revised | Post TBS | 31.5 score on a scale | Standard Deviation 23.9 |
| Sham-Active | Changes of Total Scores of Repetitive Behavior Scale-Revised | During TBS | 28.1 score on a scale | Standard Deviation 21.5 |
Primary
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.
Time frame: baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active-Active | Changes of Total Scores of Social Responsiveness Scale | Baseline | 107.3 score on a scale | Standard Deviation 24 |
| Active-Active | Changes of Total Scores of Social Responsiveness Scale | During TBS | 103.4 score on a scale | Standard Deviation 25.5 |
| Active-Active | Changes of Total Scores of Social Responsiveness Scale | Post TBS | 98.5 score on a scale | Standard Deviation 28.7 |
| Active-Active | Changes of Total Scores of Social Responsiveness Scale | One month follow up | 97.2 score on a scale | Standard Deviation 25.6 |
| Sham-Active | Changes of Total Scores of Social Responsiveness Scale | One month follow up | 94.7 score on a scale | Standard Deviation 27.9 |
| Sham-Active | Changes of Total Scores of Social Responsiveness Scale | Baseline | 102.1 score on a scale | Standard Deviation 23.2 |
| Sham-Active | Changes of Total Scores of Social Responsiveness Scale | Post TBS | 95.1 score on a scale | Standard Deviation 25.7 |
| Sham-Active | Changes of Total Scores of Social Responsiveness Scale | During TBS | 100.1 score on a scale | Standard Deviation 27.1 |
Secondary
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 (The score ranges from 0-43).
Time frame: baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active-Active | Changes in Accuracy of Eyes Task | Post TBS | 21.8 score on a scale | Standard Deviation 9 |
| Active-Active | Changes in Accuracy of Eyes Task | One month follow up | 22 score on a scale | Standard Deviation 8.6 |
| Active-Active | Changes in Accuracy of Eyes Task | Baseline | 20.8 score on a scale | Standard Deviation 8 |
| Active-Active | Changes in Accuracy of Eyes Task | During TBS | 21.9 score on a scale | Standard Deviation 8.1 |
| Sham-Active | Changes in Accuracy of Eyes Task | During TBS | 25.8 score on a scale | Standard Deviation 7 |
| Sham-Active | Changes in Accuracy of Eyes Task | Post TBS | 24.8 score on a scale | Standard Deviation 6.3 |
| Sham-Active | Changes in Accuracy of Eyes Task | Baseline | 24.8 score on a scale | Standard Deviation 6.9 |
| Sham-Active | Changes in Accuracy of Eyes Task | One month follow up | 26 score on a scale | Standard Deviation 7.1 |
Secondary
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 (The score ranges from 0-48).
Time frame: baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline); One month follow up (4 weeks after post TBS)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active-Active | Changes in Accuracy of Frith-Happe Animation | Baseline | 5.5 score on a scale | Standard Deviation 2.1 |
| Active-Active | Changes in Accuracy of Frith-Happe Animation | During TBS | 5.4 score on a scale | Standard Deviation 1.8 |
| Active-Active | Changes in Accuracy of Frith-Happe Animation | Post TBS | 5.4 score on a scale | Standard Deviation 2 |
| Active-Active | Changes in Accuracy of Frith-Happe Animation | One month follow up | 5.4 score on a scale | Standard Deviation 2.1 |
| Sham-Active | Changes in Accuracy of Frith-Happe Animation | One month follow up | 5.2 score on a scale | Standard Deviation 2.6 |
| Sham-Active | Changes in Accuracy of Frith-Happe Animation | Baseline | 5.6 score on a scale | Standard Deviation 1.9 |
| Sham-Active | Changes in Accuracy of Frith-Happe Animation | Post TBS | 5.4 score on a scale | Standard Deviation 2.3 |
| Sham-Active | Changes in Accuracy of Frith-Happe Animation | During TBS | 5.7 score on a scale | Standard Deviation 2.2 |
Secondary
Diffusion Tensor Imaging
The MRI data have to be pre-processed before analysis. It may take few years.
Time frame: baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline)
Secondary
Functional MRI (Biological Motion Task)
The MRI data have to be pre-processed before analysis. It may take few years.
Time frame: baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline)
Secondary
Resting State fMRI
The MRI data have to be pre-processed before analysis. It may take few years.
Time frame: baseline; during TBS (4 weeks after baseline); post TBS (8 weeks after baseline)