Clinical trial NCT06847165: Trigeminal Nerve Stimulation for Children With Prenatal Alcohol Exposure
Official title: Trigeminal Nerve Stimulation for Children With Prenatal Alcohol Exposure
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Fetal Alcohol Spectrum Disorders
Attention Deficit Hyperactivity Disorder
Keywords: prenatal alcohol exposure
attention deficit hyperactivity disorder
trigeminal nerve stimulation
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2025-02-26
Enrollment: 30
Sex: ALL
Minimum age (years): 8
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: open label trial
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Attention Deficit Hyperactivity Disorder (ADHD) Rating Scale Total Score
timeFrame: administered at baseline and up to 1 week after completing 4 weeks of trigeminal nerve stimulation (TNS) treatment
Secondary outcomes:
measure: Clinical Global Impression-- Severity (CGI-S) for Attention Deficit Hyperactivity Disorder (ADHD)
timeFrame: administered at baseline
measure: Clinical Global Impression-- Improvement (CGI-I) for ADHD
timeFrame: administered up to 1 week after completing 4 weeks of trigeminal nerve stimulation (TNS) treatment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: University of California Los Angeles Semel Institute Division of Child & Adolescent Psychiatry
state: California
Study officials:
affiliation: UCLA Division of Child & Adolescent Psychiatry
name: Joseph O'Neill, PhD
role: PRINCIPAL_INVESTIGATOR
References: