External Trigeminal Nerve Stimulation for Children With ASD + ADHD to Reduce Elevated Symptoms (eTNS CARES)

Phase IIa Clinical Trial of External Trigeminal Nerve Stimulation for Autistic Children With Attention Deficit/Hyperactivity Disorder

The goal of this clinical trial is to learn if external trigeminal nerve stimulation (eTNS) works to treat ADHD symptoms in children on the autism spectrum (ASD). It will also learn about the efficacy and tolerability of the eTNS device. The main questions it aims to answer are:

• Does eTNS reduce ADHD symptoms?
• Does eTNS improve core and associated features of ASD?

Participation spans 8-12 weeks and includes:

• 4-5 in-person visits
• 4 brief virtual check-ins
• Nightly use of the eTNS device with a small sticky patch applied to child's forehead
• Randomized assignment (those who start with the sham device may try the active device later)

Study Overview

• Status: Recruiting
• Conditions: Attention Deficit Disorder With Hyperactivity (ADHD); Autism Spectrum Disorder (ASD)
• Intervention / Treatment: Device: Trigeminal Nerve Stimulation; Device: Sham Trigeminal Nerve Stimulation

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94107
      • Recruiting
      • UCSF Nancy Friend Pritzker Psychiatry Building
      • Principal Investigator: James McCracken, MD
      • Contact: Jazzy Benes, MS; Phone Number: 4154768803; Email: jazzy.benes@ucsf.edu

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Confirmed clinician diagnosis of ASD according to DSM-5 criteria, corroborated by prior testing (or obtained in study screening) with the Autism Diagnostic Observation Schedule (ADOS) with or without the Autism Diagnostic Interview-Revised (ADI-R)
• IQ > 70 as corroborated by prior testing (or obtained in study screening) with the Wechsler Abbreviated Scale of Intelligence Scale (WASI)
• Confirmed diagnosis of ADHD according to DSM-5 criteria with minimum ADHD-RS score of > 24
• Stable on current medications for a minimum of 4 weeks before baseline
• Ability to complete protocol testing
• Both the child participant and their primary caregiver must be fluent in English (speaking, reading, and understanding), as the questionnaires and assessment tools used in this study have been validated only in English.

Exclusion Criteria:

• Current major depression, history of psychosis, bipolar disorder, elevated risk of self-harm
• History of moderate to severe coarse brain injury
• Active medical illness expected to interfere with study assessments
• Presence of implanted stimulator (e.g., vagal nerve stimulator)
• Active dermatologic condition likely to interfere with eTNS electrode wearability
• Sleep disorder likely to interfere with nightly eTNS in the opinion of the study physician
• Inability to communicate discomfort or pain
• Current and anticipated continued use of antipsychotic or stimulant medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Active eTNS Device	Device: Trigeminal Nerve Stimulation; This intervention is expected to have an effect following a treatment period of 6 weeks.
Sham Comparator: Sham eTNS Device	Device: Sham Trigeminal Nerve Stimulation; This intervention is NOT expected to have an effect following a treatment period of 6 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in ADHD Symptoms	Examine the efficacy of external Trigeminal Nerve Stimulation (eTNS) in reducing ADHD symptoms as measured by the Attention-Deficit/Hyperactivity Disorder Rating Scale-5 (ADHD-RS-5; range 0-54), where higher scores indicate worse symptoms.	Baseline to end of treatment at 6 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Social Responsiveness	Examine changes in social communication and related behaviors as measured by the Social Responsiveness Scale, Second Edition, Short Form (SRS-2-SF; range 0-48), where higher scores indicate worse impairment.	Baseline to end of treatment at 6 weeks
Change in Restricted and Repetitive Behaviors	Examine changes in restricted and repetitive behaviors as measured by the Repetitive Behavior Scale-Revised (RBS-R; range 0-129), where higher scores indicate more severe repetitive behaviors.	Baseline to end of treatment at 6 weeks
Change in Sleep Quality	Examine changes in sleep quality as measured by the Children's Sleep Habits Questionnaire (CSHQ; range 33-99), where higher scores indicate poorer sleep quality.	Baseline to end of treatment at 6 weeks

Collaborators and Investigators

• Sponsor: University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): October 6, 2025
• Primary Completion (Estimated): September 1, 2027
• Study Completion (Estimated): January 31, 2028

Study Registration Dates

• First Submitted: September 11, 2025
• First Submitted That Met QC Criteria: October 7, 2025
• First Posted (Estimated): October 9, 2025

Study Record Updates

• Last Update Posted (Estimated): October 9, 2025
• Last Update Submitted That Met QC Criteria: October 7, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: eTNS; external trigeminal nerve stimulation; eTNS CARES
• Additional Relevant MeSH Terms: Mental Disorders; Neurodevelopmental Disorders; Child Development Disorders, Pervasive; Attention Deficit and Disruptive Behavior Disorders; Autism Spectrum Disorder; Attention Deficit Disorder with Hyperactivity
• Other Study ID Numbers: 25-44041

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes