Auricular Transcutaneous Electrical Nerve Stimulation Treatment of Autism

Study Overview
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Brief Summary
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In this study, investigators will examine the treatment effects of transcutaneous electrical nerve stimulation with different stimulation frequencies on individuals with autism.

Detailed Description
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In this study, investigators will examine the treatment effect of transcutaneous electrical nerve stimulation at auricular area with vagus nerve distribution on high-functioning individuals with autism. Specifically, investigators will choose two ear acupoints: heart and shenmen. Participants will be randomized to either 1 Hz or 20 Hz tVNS group (up to 5 times per week) for three weeks.

Official Title
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Auricular Transcutaneous Electrical Nerve Stimulation Treatment of Autism

Conditions
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Autism Spectrum Disorder

Intervention / Treatment
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* Other: 1 Hz Auricular transcutaneous electrical nerve stimulation
* Other: 20 Hz Auricular transcutaneous electrical nerve stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Autism diagnosed based on DSM-V classification criteria 18-60 year old high functioning adult autism patients (e.g. Asperger's, IQ equal or greater than 80) Subjects who do not show aggressive behaviors based on neuro/psychiatric evaluations as determined by a licensed study physician. Exclusion Criteria: A history of chronic serious infection, any current infection, any type of cancer or autoimmune disease or other severe diseases; Subjects taking any medications that confound the study results

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1 Hz group<br>1 Hz Auricular transcutaneous electrical nerve stimulation High-functioning individuals with autism randomized to this group will receive 1 Hz tVNS stimulation for 30 minutes/day up to 5 times/week for 3 weeks. | Other: 1 Hz Auricular transcutaneous electrical nerve stimulation<br>* High-functioning individuals with autism randomized to this group will receive 1 Hz tVNS stimulation for 30 minutes/day up to 5 times/week for 3 weeks.<br>|
| Active Comparator: 20 Hz group<br>20 Hz Auricular transcutaneous electrical nerve stimulation High-functioning individuals with autism randomized to this group will receive 20 Hz tVNS stimulation for 30 minutes/day up to 5 times/week for 3 weeks. | Other: 20 Hz Auricular transcutaneous electrical nerve stimulation<br>* High-functioning individuals with autism randomized to this group will receive 1 Hz tVNS stimulation for 30 minutes/day up to 5 times/week for 3 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Autism Treatment Evaluation Checklist (ATEC) | ATEC will be reported by investigator in a total and for each of the 4 subscales as follows: (1) speech/language/communication subscale; (2) social subscale; (3) sensory and cognitive awareness subscale; and (4) health / physical / behavior problem subscale. The total score ranges from 0 to 179; a higher score indicated worsening while a lower score indicated improvement. | Baseline and after 3-week treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Aberrant Behavior Checklist (ABC) | The factors of the ABC have been labeled as follows: (I) Irritability, Agitation, Crying; (II) Lethargy, Social Withdrawal; (III) Stereotypic Behavior; (IV) Hyperactivity, Noncompliance; and (V) Inappropriate Speech. | Baseline and after 3-week treatment | 
| Change in Clinical Global Impression-Improvement (CGI-I) | Overall improvement in autism will be assessed using the Clinical Global Impression-Improvement (CGI-I) scale, a 7-point scale from 1 = very much improved to 7 = very much worse. | Baseline and after 3-week treatment | 
| Change in PROMIS Sleep Disturbance Short Form | This questionnaire is used to assess the pure domain of sleep disturbance in adults. | Baseline and after 3-week treatment | 
| Change in Penn State Worry Questionnaire | This is the standard assessment of worry and consists of 16 questions rated from 1 to 5 from Not typical of me to Very typical of me. | Baseline and after 3-week treatment | 
| Change in Sleep Quality Assessment (PSQI) | The Pittsburgh Sleep Quality Index (PSQI) is an effective instrument used to measure the quality and patterns of sleep in adults. It differentiates poor from good sleep quality by measuring seven areas (components): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction over the last week. | Baseline and after 3-week treatment | 
| PROMIS-29 | The PROMIS-29 assesses pain intensity, physical function, depression, anxiety, fatigue, sleep disturbance, interference, and social role and activity in the past 7 days | Baseline and after 3-week treatment | 
| EEG (optional) | Resting state EEG (filter 1-50 Hz) will be collected | Baseline and after 3-week treatment | 
| Salivary oxytocin quantification (optional) | A total of 4-mL of unstimulated saliva will be collected | Baseline and after 3-week treatment | 
| Quantification of species-level L. reuteri abundance in human stool samples (optional) | Stool samples will be collected at home following our provided instructions. | Baseline and after 3-week treatment | 
| Autonomic measurements via wristband photoplethysmograph (PPG) sensor (optional) | 6 minutes PPG data will be collected | Baseline and after 3-week treatment | 
| ECG (optional) | 6 minutes raw ECG data will be collected for Heart rate variability (HRV) analysis | Baseline and after 3-week treatment | 
| Pulse oximetry measurements (optional) | SpCO will be measured at different time points | Baseline and after 3-week treatment |