Trigeminal Nerve Stimulation for Children With Prenatal Alcohol Exposure (TNS-PAE)

This is an open-label trial of trigeminal nerve stimulation (TNS) for children aged 8-12 years with attention deficit hyperactivity disorder (ADHD) putatively due to prenatal alcohol exposure (PAE). TNS has been successful in treating pediatric ADHD generally and it is US Food and Drug Administration (FDA)-cleared for this condition. But this will be the first time it is tried for ADHD specifically associated with PAE. In TNS, a weak electric current is applied to the child's forehead overnight while sleeping to gently stimulate the brain. TNS is administered at home by the parent to the child. TNS is safe and well tolerated. Efficacy of TNS in ADHD is ~50%. The purpose of the present pilot study is to determine the feasibility of TNS for children with PAE and ADHD. Feasibility means safety (any serious side effects?), tolerability (do children comply with TNS? are they comfortable with it?), and a rough idea of efficacy (does TNS seem to work in most kids?) A secondary goal of the study is to get a more precise idea of brain mechanisms of TNS with magnetic resonance imaging (MRI). Families who participate will make three clinic visits: eligibility (4-5 hours), pre-TNS (2-3 hours including MRI), and post-TNS (2-3 hours including MRI). Children will receive TNS, applied by the parent, for 8 hours every night while sleeping for 4 weeks. Four weeks after treatment, families will take part in a telephone follow-up, to see whether any improvements made last.

Study Overview

• Status: Recruiting
• Conditions: Attention Deficit Hyperactivity Disorder; Fetal Alcohol Spectrum Disorders
• Intervention / Treatment: Device: Trigeminal Nerve Stimulation (TNS)

Detailed Description

Trigeminal nerve stimulation (TNS) is a new treatment for pediatric ADHD developed at University of California Los Angeles (UCLA). In TNS, a weak electric current is applied to the child's forehead overnight while sleeping to gently stimulate the brain. TNS treatment is typically administered at home at bedtime by the parent to the child. The TNS device is small (size of a cell phone) and easy to use. Two thin wires go from the device to a pair of small electrodes that tape onto the forehead like a band-aid. The parent presses three keys on the device and it is ready to go. TNS is safe and well tolerated. The success rate, or efficacy, of TNS is about 50% in children with ADHD overall. Although TNS is FDA-cleared for children with ADHD, regardless of the cause, or etiology, of the ADHD, the possible influence of etiology on TNS success has not yet been studied. One common etiology of ADHD is prenatal alcohol exposure (PAE). When a mother drinks alcohol during pregnancy her child often develops ADHD. While TNS is an approved treatment for these children, it is actually not known whether they would respond any differently. It is known that drug treatments that routinely work well in children with ADHD without PAE are poorly effective in many children with ADHD due to PAE. Thus, there is a chance children with ADHD due to PAE could respond differently (better or worse) to TNS as well. The purpose of the research is to determine the safety and efficacy of TNS specifically in children whose ADHD is associated with PAE. We expect that TNS will be as safe and effective in children with ADHD with PAE as in children without, but that needs to be formally tested. As a first step in the formal testing process, this pilot study aims to determine the feasibility of TNS in children with ADHD associated with PAE. Feasibility means safety (any serious side effects?), tolerability (do children comply with TNS? are they comfortable with it?), and a rough idea of efficacy (does TNS seem to work in most kids?) A secondary goal of our study is to get a more precise idea of where and how TNS acts in the brain using MRI-based neuroimaging. Families who participate in the study will come to the clinic for three visits: eligibility (4-5 hours), pre-TNS (2-3 hours including MRI), and post-TNS (2-3 hours including MRI). Thus, the child will undergo two MRIs of the brain, a safe, non-invasive, and radiation-free procedure. The child will receive TNS treatment, applied by the parent, for 8 hours every night while sleeping for 4 weeks. Four weeks after treatment, families will take part in a telephone follow-up, to see whether any improvements made last.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joseph O'Neill, PhD; Phone Number: (310) 825-5709; Email: joneill@mednet.ucla.edu
• Study Contact Backup: Name: Ishika B Gupta, BS; Phone Number: (310) 267-2710; Email: ChildBrainStudy@mednet.ucla.edu

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90024
      • Recruiting
      • University of California Los Angeles Semel Institute Division of Child & Adolescent Psychiatry
      • Contact: Lindy B Comstock, PhD; Email: ChildBrainStudy@mednet.ucla.edu
      • Contact: Joseph O'Neill, PhD; Phone Number: (310) 825-5709; Email: ChildBrainStudy@mednet.ucla.edu
      • Principal Investigator: Joseph O'Neill, PhD
      • Sub-Investigator: Mary J O'Connor, PhD
      • Sub-Investigator: Benjamin N Schneider, MD
      • Sub-Investigator: Jeffry R Alger, PhD
      • Sub-Investigator: Shantanu Joshi, PhD
      • Sub-Investigator: Lindy B Comstock, PhD
      • Sub-Investigator: Andrew F Leuchter, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• - Fetal alcohol syndrome, partial fetal alcohol syndrome, or alcohol-related neurodevelopmental disorder per modified Institute of Medicine criteria (thus positive maternal drinking in pregnancy required, facial stigmata not required)
• Prenatal alcohol exposure (PAE) >6 drinks/week for >= 2 weeks and/or >= 3 drinks on >= 2 occasions throughout gestation per Health Interview for Women/Health Interview for Adoptive and Foster Parents (HIW/HIAFP)
• Diagnosis of Diagnostic and Statistical Manual 5th edition (DSM-5) attention deficit hyperactivity disorder (ADHD), including problems with inattention, hyperactivity, impulsivity, and/or executive function. Screening for ADHD will be done using the Swanson, Nolan, and Pelham Teacher and Parent Rating Scale (SNAP IV). Formal diagnosis of ADHD will be based on the Mini-International Neuropsychiatric Interview for Children and Adolescents (MINI-KID) with input from the Behavior Rating of Executive Function (BRIEF II) and the Conners 4.
• Parent and child able to complete testing in English
• Child able to cooperate during MRI
• Full-Scale Intelligence Quotient >70 per the Kaufman Brief Intelligence Test (K-BIT-2)
• Child able to comply with study procedures
• Age 8-12

Exclusion Criteria:

• - Other toxic exposure per HIW/HIAFP whose influence clearly surpasses that of alcohol (very rare) per study clinician judgement
• Known genetic syndrome associated with ADHD-like symptoms including fragile X, tuberous sclerosis, or generalized resistance to thyroid hormone
• Serious medical or neurologic illness likely to influence brain function, e.g., seizures, closed-head trauma
• Gestation < 34 weeks
• Ferromagnetic metal, claustrophobia, or other MRI or TNS contraindication (e.g., insulin pumps or other body-worn devices)
• Diagnosis of autism spectrum disorder, psychotic disorder, or major mood disorder
• Active suicidal ideation as evidenced by meeting criteria for "Current" or "Lifetime attempt" on the Suicidality module or "Current' or 'In early remission' on the Suicide Behavior Disorder module of the MINI KID

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Trigeminal Nerve Stimulation; Each child will receive nightly trigeminal nerve stimulation, administered by the parent at bedtime, for 8 hrs while sleeping overnight, nightly for 4 weeks (28 days)

Device: Trigeminal Nerve Stimulation (TNS); In TNS, a weak electric current is applied to the child's forehead overnight while sleeping to gently stimulate the brain. TNS treatment is typically administered at home at bedtime by the parent to the child. The TNS device is small (size of a cell phone) and easy to use. Two thin wires go from the device to a pair of small electrodes that tape onto the forehead like a band-aid. The parent presses three keys on the device and it is ready to go.; Other Names: external trigeminal nerve stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale Total Score	clinician-administered measure of severity of core ADHD symptoms: inattention and hyperactivity/impulsivity; minimum score 0, maximum score 40, a higher score means a worse outcome	administered at baseline and up to 1 week after completing 4 weeks of trigeminal nerve stimulation (TNS) treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Global Impression-- Severity (CGI-S) for Attention Deficit Hyperactivity Disorder (ADHD)	This is clinician-administered measure of overall severity of ADHD symptoms: minimum score 1, maximum score 7; higher score is worse outcome	administered at baseline
Clinical Global Impression-- Improvement (CGI-I) for ADHD	CGI-I: minimum score 1, maximum score 7; higher score is worse outcome	administered up to 1 week after completing 4 weeks of trigeminal nerve stimulation (TNS) treatment

Collaborators and Investigators

• Sponsor: University of California, Los Angeles
• Collaborators: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
• Investigators: Principal Investigator: Joseph O'Neill, PhD, UCLA Division of Child & Adolescent Psychiatry

Study record dates

Study Major Dates

• Study Start (Actual): April 26, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026

Study Registration Dates

• First Submitted: February 16, 2025
• First Submitted That Met QC Criteria: February 20, 2025
• First Posted (Actual): February 26, 2025

Study Record Updates

• Last Update Posted (Estimated): July 1, 2025
• Last Update Submitted That Met QC Criteria: June 29, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: attention deficit hyperactivity disorder; trigeminal nerve stimulation; prenatal alcohol exposure
• Additional Relevant MeSH Terms: Urogenital Diseases; Neurologic Manifestations; Nervous System Diseases; Mental Disorders; Female Urogenital Diseases and Pregnancy Complications; Pregnancy Complications; Fetal Diseases; Substance-Related Disorders; Chemically-Induced Disorders; Alcohol-Related Disorders; Neurodevelopmental Disorders; Attention Deficit and Disruptive Behavior Disorders; Dyskinesias; Alcohol-Induced Disorders; Hyperkinesis; Attention Deficit Disorder with Hyperactivity; Fetal Alcohol Spectrum Disorders
• Other Study ID Numbers: IRB-24-0648; R61AA031029 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Trial data will be posted to the National Institute on Alcohol Abuse and Alcoholism (NIAAA) Data Archive
• IPD Sharing Time Frame: Data posted to the NIAAA Data Archive will be updated every 6 months after enrollment of the first subject. Data will remain posted in perpetuity or until the Archive takes them down.
• IPD Sharing Access Criteria: Any investigator with access to the NIAAA Data Archive will have access to the data.

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