Trigeminal Nerve Stimulation for Children With Prenatal Alcohol Exposure

NCT ID: NCT06847165

Last Updated: 2025-07-01

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-04-26
• Study Completion Date: 2026-09-30

Brief Summary

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.

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.

Conditions

Fetal Alcohol Spectrum Disorders; Attention Deficit Hyperactivity Disorder

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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)

Group Type: EXPERIMENTAL

Trigeminal Nerve Stimulation (TNS)

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: DEVICE

Other Intervention Names

external trigeminal nerve stimulation

Eligibility Criteria

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

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Joseph O'Neill, PhD

Professor of Child Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Joseph O'Neill, PhD

Role: PRINCIPAL_INVESTIGATOR

UCLA Division of Child & Adolescent Psychiatry

Locations

University of California Los Angeles Semel Institute Division of Child & Adolescent Psychiatry

Los Angeles, California, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Ishika B Gupta, BS

Role: CONTACT

ChildBrainStudy@mednet.ucla.edu

(310) 267-2710

Joseph O'Neill, PhD

Role: CONTACT

joneill@mednet.ucla.edu

(310) 825-5709

Facility Contacts

Lindy B Comstock, PhD

Role: primary

ChildBrainStudy@mednet.ucla.edu

Joseph O'Neill, PhD

Role: backup

ChildBrainStudy@mednet.ucla.edu

(310) 825-5709

References

O'Neill J, Joshi S, Alger JR, Leuchter AF, Schneider BN, O'Connor MJ. Trigeminal nerve stimulation (TNS) for children with attention deficit/hyperactivity disorder and fetal alcohol spectrum disorder: Feasibility study protocol. PLoS One. 2025 Aug 29;20(8):e0330986. doi: 10.1371/journal.pone.0330986. eCollection 2025.

Reference Type: DERIVED

PMID: 40880352 (View on PubMed)

O'Neill J, Joshi S, Alger JR, Schneider BN, O'Connor MJ. Trigeminal Nerve Stimulation (TNS) for Children with Attention Deficit/Hyperactivity Disorder and Fetal Alcohol Spectrum Disorder: Feasibility Study Protocol. medRxiv [Preprint]. 2025 Jul 7:2025.07.07.25331025. doi: 10.1101/2025.07.07.25331025.

Reference Type: DERIVED

PMID: 40672490 (View on PubMed)

Other Identifiers

R61AA031029

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB-24-0648

Identifier Type: -

Identifier Source: org_study_id