Transcranial Temporal Interference Stimulation for Children With Autism Spectrum Disorders

Individualized Targeted Transcranial Temporal Interference Stimulation for Children With Autism Spectrum Disorder: A Single-Blinded, Randomized, Controlled Exploratory Trial

The goal of this single-blinded, randomized controlled trial is to assess the safety, tolerability, and feasibility of tTIS for children with ASD. The main question it aims to answer is:

- Is tTIS safe, tolerable, and feasible for use for children with autism spectrum disorder?

Researchers will compare tTIS group with control group to explore the safety and feasibility of the transcranial electrical stimulation for children with autism.

Participants will:

• tTIS group: undergo 5 days of temporal tTIS.
• Sham group: undergo 5 days of temporal tTIS without low-frequency envelope.

From baseline to 4 weeks after intervention completion, subjects will be followed up regarding clinical symptoms and adverse events:

• Primary Outcome Measures: Safety and feasibility of tTIS, assessed by adverse events, treatment completion rate, adherence to the stimulation protocol and tolerability.
• Secondary/Exploratory Outcome Measures: Changes in SRS-2 total scores and other clinical measures related to language, adaptive functioning, and cognition.

Study Overview

• Status: Recruiting
• Conditions: Autism Spectrum Disorder
• Intervention / Treatment: Device: transcranial Temporal Interference Stimulation

Detailed Description

This research is a 5-week single-blinded, randomized controlled trial, planning to enroll 16 ASD children aged 4-10 with a full-scale intelligence quotient (FSIQ) of 50 or above. Children who satisfy all inclusion criteria without meeting any exclusion criteria, may be enrolled after their legal guardians provided the written informed consent.

Eligible subjects will be randomly divided into two groups: tTIS group and sham group. The tTIS group will undergo 5 days of temporal TI stimulation (1.5mA, 2040/2000Hz, 20min/session, 6 sessions/day); the control group will undergo 5 days of temporal TI stimulation (1.5mA, 2000/2000Hz, 20min/session, 6 sessions/day, without 40Hz envelope compared to tTIS group)

At baseline, subjects will undergo physical measurements, demographic and medical history collection, intelligence test and symptom clinical scale assessments, and resting-state EEG collection. From the start of intervention until 4 weeks after completion, subjects will be followed up regarding clinical symptoms, neuroimaging, and adverse events.

Primary Outcome Measures:

- Safety and feasibility of tTIS, assessed by adverse events, treatment completion rate, adherence to the stimulation protocol and tolerability.

Secondary outcomes:

• Change in Social Responsiveness Scale, Second Edition (SRS-2) total score from baseline to immediately after completion of the 5-day intervention.
• Change in SRS-2 total score from baseline to 4 weeks after completion of the 5-day intervention.
• Changes in other clinical measures from baseline to 4 weeks after completion of the 5-day intervention, including the Chinese Communicative Development Inventory (CCDI), Childhood Autism Rating Scale (CARS), Peabody Picture Vocabulary Test (PPVT), selected subtests of A Developmental Neuropsychological Assessment, Second Edition (NEPSY-II; Narrative Memory, Memory for Faces, Theory of Mind, Word Generation, and Affect Recognition), and Clinical Global Impression (CGI) scale scores.

Exploratory Outcomes:

- resting-state and task-state EEG neuroimaging characteristics before intervention, immediately after the 5-day intervention, and 4 weeks after completion of the 5-day intervention

• Study Type: Interventional
• Enrollment (Estimated): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai Municipality
    • Shanghai, Shanghai Municipality, China, 200092
      • Recruiting
      • Fei Li
      • Contact: Fei Li, PHD, MD; Phone Number: +86-21-25077461; Email: feili@shsmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Children aged 4-10 years
• Meeting the diagnostic criteria for ASD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) and confirmed by the Autism Diagnostic Observation Schedule (ADOS) and/or the Autism Diagnostic Interview-Revised (ADI-R)
• Full Scale Intelligence Quotient (FSIQ) ≥50
• Signed informed consent form

Exclusion Criteria:

• Individuals with metal implants in the body
• Individuals with neurological disorders such as epilepsy
• Those requiring surgical treatment due to structural abnormalities indicated by brain MRI examination
• Those diagnosed with genetic or chromosomal abnormalities
• Individuals with mental illness (such as early-onset schizophrenia)
• Those with severe cardiac disease
• Individuals with increased intracranial pressure
• Those currently participating in other clinical trials
• Those who received new intervention protocols within 4 weeks prior to enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention group (tTIS); Receive tTIS targeting the anterior middle temporal gyrus, with stimulation frequency of 2040/2000HZ, using battery power supply: voltage 12V, current set at 1.5mA, 6 times/day, 20min/session with 20min intervals between sessions, lasting for 5 days	Device: transcranial Temporal Interference Stimulation; Receive tTIS targeting the anterior middle temporal gyrus with stimulation frequency of 2040/2000HZ, using battery power supply: voltage 12V, current set at 1.5mA, 6 times/day, 20min/session with 20min intervals between sessions, lasting for 5 days.
Sham Comparator: Control group; Receive tTIS targeting the anterior middle temporal gyrus, with stimulation frequency of 2000/2000HZ(without 40Hz envelope compared to tTIS group), using battery power supply: voltage 12V, current set at 1.5mA, 6 times/day, 20min/session with 20min intervals between sessions, lasting for 5 days	Device: transcranial Temporal Interference Stimulation; Receive tTIS targeting the anterior middle temporal gyrus with stimulation frequency of 2040/2000HZ, using battery power supply: voltage 12V, current set at 1.5mA, 6 times/day, 20min/session with 20min intervals between sessions, lasting for 5 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Completion of the tTIS intervention protocol	The proportion of participants who complete all scheduled tTIS sessions according to the predefined stimulation protocol during the 5-day intervention.	During the 5-day intervention
Number of participants with adverse events	The number and proportion of participants who experience adverse events during the study period.	From the start of the intervention to 4 weeks after completion of the 5-day intervention.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SRS-2	Change from baseline in SRS-2 score immediately after the 5-day intervention. The SRS-2 is primarily used to assess symptoms associated with ASD. Compared to other autism assessment tools, the SRS-2 stands out for its focus on quantifying the severity of social impairment, with higher scores indicating more autism symptoms and greater social disability.	Baseline, after completion of 5-day intervention
Childhood Autism Rating Scale (CARS)	Change in CARS score from baseline to 4 weeks after the 5-day intervention. CARS is a behavior rating scale used to assess the presence and severity of the symptoms associated autism spectrum disorder. The scores of the CARS rate from 15 to 60, and higher scores indicate more severe symptoms. The changes in the CAR scores from baseline to 3 months after the treatment will be analyzed to asses the impact often intervention on participants with ASD.	Baseline, 4 weeks after completion of 5-day intervention
Social Responsiveness Scale, Second Edition (SRS-2)	Change in SRS-2 score from baseline to 4 weeks after completion of the 5-day intervention.The SRS-2 is primarily used to assess symptoms associated with ASD. Compared to other autism assessment tools, the SRS-2 stands out for its focus on quantifying the severity of social impairment, with higher scores indicating more autism symptoms and greater social disability.	Baseline, 4 weeks after completion of 5-day intervention
Chinese Communicative Development Inventory, CCDI	Change in CCDI score from baseline to 4 weeks after the 5-day intervention.Chinese Communicative Development Inventory(CCDl) is a questionnaire used to measures the language abilities. Higher scores suggest better language level. The changes in the CCDl between baseline and 3 month after treatment will be analyzed.	Baseline, 4 weeks after completion of 5-day intervention
Peabody Picture Vocabulory Test, PPVT	Change in PPVT score from baseline to 4 weeks after the 5-day intervention. PPVT as a tool for measuring children's language receptive ability and language comprehension ability.	Baseline, 4 weeks after completion of 5-day intervention
Neuropsychological Assessment for Child, NEPSY-II	Change in NEPSY-II score from baseline to 4 weeks after the 5-day intervention. NEPSY-II is a comprehensive neuropsychological measurement tool used for assessing neuro-cognitive functions in children aged 3-16 years. This study primarily evaluates the following aspects: narrative memory assessment, facial memory assessment, theory of mind, word generation, affection recognition.	Baseline, 4 weeks after completion of 5-day intervention
Vineland Adaptive Behavior Scales-Third Edition, Vineland-3	Change in VABS-3 score from baseline to 4 weeks after the 5-day intervention. The VABS-3 is used to measure adaptive functioning across domains such as communication,daily living skills, socialization, and motor skills. Changes in VABs scores from baseline to 3 months post-treatment will be analyzed to assess the intervention's impact on adaptive behaviors in children with ASD.	Baseline, 4 weeks after completion of 5-day intervention
Clinical Global Impression Scale (CGI)	The Clinical Global Impressions (CGI) scale is used to assess both the severity of illness and the global improvement of participants undergoing intervention.	after completion of 5-day intervention, four weeks after completion of 5-day intervention
Multilingual Assessment Instrument for Narratives (MAIN)	Change in MAIN score from baseline to 4 weeks after the 5-day intervention. MAIN assess narrative comprehension and production skills of children who exhibited a certain level of expressive ability (at least can use flexible phrases). In this test, children tell or retell the stories and answer some questions, with assessors evaluating performance. Higher scores suggest better language level.	Baseline, 4 weeks after completion of 5-day intervention

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in alpha-band EEG power	Change in alpha-band EEG power from baseline to immediately after completion of the 5-day intervention and to 4 weeks after completion of the 5-day intervention.	Baseline, immediately after completion of the 5-day intervention, and 4 weeks after completion of the 5-day intervention.
Change from baseline in theta-band EEG power	Change in theta-band EEG power from baseline to immediately after completion of the 5-day intervention and to 4 weeks after completion of the 5-day intervention.	Baseline, immediately after completion of the 5-day intervention, and 4 weeks after completion of the 5-day intervention.
Change from baseline in inter-trial phase coherence in the alpha band	Change in alpha-band inter-trial phase coherence from baseline to immediately after completion of the 5-day intervention and to 4 weeks after completion of the 5-day intervention.	Baseline, immediately after completion of the 5-day intervention, and 4 weeks after completion of the 5-day intervention.
Change from baseline in inter-trial phase coherence in the theta band	Change in theta-band inter-trial phase coherence from baseline to immediately after completion of the 5-day intervention and to 4 weeks after completion of the 5-day intervention.	Baseline, immediately after completion of the 5-day intervention, and 4 weeks after completion of the 5-day intervention.

Collaborators and Investigators

• Sponsor: Xinhua Hospital, Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Estimated): May 25, 2026
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): October 5, 2026

Study Registration Dates

• First Submitted: May 19, 2026
• First Submitted That Met QC Criteria: May 29, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 29, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Autism Spectrum Disorder
• Other Study ID Numbers: XHEC-C-2026-109-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The study Protocol, statistical Analysis plan, informed Consent Form, and other relevant documents will be available under reasonable and ethically approved request to the corresponding authors.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No