Trigeminal Nerve Stimulation for Children With Prenatal Alcohol Exposure

NCT06847165 | Recruiting DMC FDA Device

• 2 other identifiers: IRB-24-0648R61AA031029
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

Fetal Alcohol Spectrum Disorders; Attention Deficit Hyperactivity Disorder

Keywords

prenatal alcohol exposure; attention deficit hyperactivity disorder; trigeminal nerve stimulation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Clinical Global Impression-- Severity (CGI-S) for Attention Deficit Hyperactivity Disorder (ADHD)

  administered at baseline

• Clinical Global Impression-- Improvement (CGI-I) for ADHD

  administered up to 1 week after completing 4 weeks of trigeminal nerve stimulation (TNS) treatment

Study Arms (1)

Trigeminal Nerve Stimulation

EXPERIMENTAL

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)

Interventions

Trigeminal Nerve Stimulation (TNS) 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.

Also known as: external trigeminal nerve stimulation

Trigeminal Nerve Stimulation

Eligibility Criteria

• Age: 8 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• \- 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

You may not qualify if:

• \- 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

Sponsors & Collaborators

• University of California, Los Angeles: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

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

Los Angeles, California, 90024, United States

RECRUITING

Related Publications (2)

• 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.

  PMID: 40880352 DERIVED

• 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.

  PMID: 40672490 DERIVED

MeSH Terms

Conditions

Fetal Alcohol Spectrum Disorders; Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Fetal Diseases; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Alcohol-Induced Disorders; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Joseph O'Neill, PhD

  UCLA Division of Child & Adolescent Psychiatry

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ishika B Gupta, BS

CONTACT

(310) 267-2710; ChildBrainStudy@mednet.ucla.edu

Joseph O'Neill, PhD

CONTACT

(310) 825-5709; joneill@mednet.ucla.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Child Psychiatry

Model Details: open label trial

Study Record Dates

• First Submitted: February 16, 2025
• First Posted: February 26, 2025
• Study Start: April 26, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): September 30, 2026
• Last Updated: July 1, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• 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.
• Access Criteria: Any investigator with access to the NIAAA Data Archive will have access to the data.

Locations

US (1)