Efficacy of Trigeminal Nerve Stimulation for ADHD

NCT05374187 | Completed DMC FDA Device

• 2 other identifiers: NIHM R01 MH126041-01A11R01MH126041-01A1
• Study Type: interventional
• Target: 218
• Locations: 1 country
• Sites: 2

Brief Summary

This study is a large multisite randomized clinical trial to asses the efficacy of external trigeminal nerve stimulation (TNS), a novel, minimal risk, non-invasive neuromodulation treatment, for ADHD in children ages 7-12 years old (N=180). Study hypotheses address potential differences in ADHD symptoms over 4 weeks treatment with active vs. sham TNS in an expanded multi-site investigation; whether resting state fronto-parietal connectivity mediates TNS impact on ADHD symptoms; if changes in fronto-parietal activation, as measured by electroencephalography (EEG), predict TNS-related treatment outcomes; and whether a baseline cognitive profile similarly predicts response to TNS therapy.

Conditions

Attention-Deficit Hyperactivity Disorder

Keywords

ADHD; Neuromodulation; Trigeminal Nerve Stimulation; Cognition; EEG

Outcome Measures

Primary Outcomes (1)

• Change in ADHD Rating Scale-5 (ADHD-RS-5)

  A dimensional rating of ADHD symptoms, with scores ranging from 0-54, and higher scores indicating worse outcomes.

  Baseline, weeks 1, 2, 3, 4, 5, 6, 7, 8, 16, 20

Secondary Outcomes (9)

• Clinical Global Impression - Severity (CGI-S)

  Baseline, weeks 4, 8, 16, 20

• Clinical Global Impression - Improvement (CGI-I)

  Weeks 1, 2, 3, 4, 5, 6, 7, 8, 16, 20

• Change in Strengths and Weakness of Attention-Deficit/Hyperactivity (SWAN) Rating Scale

  Baseline, weeks 1, 2, 3, 4, 5, 6, 7, 8, 16, 20

• Change in Conners Short Form - Parent

  Baseline, weeks 4, 8

• Change in Conners Short Form - Teacher

  Baseline, weeks 4, 8

Other Outcomes (5)

• Change in Electroencephalography (EEG)

  Baseline, weeks 4, 8, 16

• Change in Attention Network Task - Go/NoGo

  Baseline, weeks 4, 8

• Change in Behavior Rating Inventory of Executive Functioning (BRIEF)

  Baseline, weeks 1, 2, 3, 4, 5, 6, 7, 8, 16, 20

Study Arms (2)

Active eTNS

EXPERIMENTAL

Following screening and determination of eligibility , participants at baseline are randomized to receive 4 weeks nightly treatment with active eTNS. Positive responders will be invited to participate in a 12-month open-label continuation phase.

Device: Active eTNS

Sham eTNS

SHAM COMPARATOR

Following screening and determination of eligibility, participants at baseline are randomize to receive 4 weeks nightly treatment with sham eTNS. At conclusion of the double-blind phase, participants randomized to sham will be provided an opportunity to receive an additional 4 weeks nightly treatment with active eTNS. Positive responders to active eTNS will be invited to participate in a 12-month open-label continuation phase.

Device: Active eTNS; Device: Sham eTNS

Interventions

Active eTNS DEVICE

Participants will receive active trigeminal nerve stimulation (eTNS) administered by the Monarch eTNS system nightly during sleep for 4 weeks. Participants deemed to be positive responders to blinded active treatment will be invited to continue open nightly eTNS in a 12 month extension period.

Also known as: Trigeminal Nerve Stimulation, Monarch eTNS SystemTM (NeuroSigma, Inc., Los Angeles, CA

Active eTNS; Sham eTNS

Sham eTNS DEVICE

Participants will receive sham trigeminal nerve stimulation (eTNS) administered by the Monarch eTNS system nightly during sleep for 4 weeks. At conclusion of the blinded trial, participants randomized to the sham group will be offered 4 weeks of open active eTNS treatment. Participants deemed to be positive responders to open active treatment will be invited to continue open nightly eTNS in a 12 month extension period.

Sham eTNS

Eligibility Criteria

• Age: 7 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• male and female children ages 7 to 12 years with DSM-5 ADHD, any current presentation, as determined by diagnostic interview, Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS), and clinical interview;
• total score \>= 24 on baseline ADHD-RS;
• CGI-S score at baseline \>= 4;
• no current medication with CNS effects (Participants previously on psychostimulant medication will be required to be not optimally treated and off medication for one week or 5 half-lives for all other medications); stable use of supplements will be permitted;
• parents able and willing to monitor proper use of the stimulation device and complete all required rating scales;
• estimated Full Scale IQ \>= 80 based on WASI subtests;
• parent and participant able to complete rating scales and other measures in English;
• able to cooperate during EEG

You may not qualify if:

• impaired functioning to a degree that requires immediate initiation of ADHD medication in the opinion of the parents and/or investigator;
• current diagnosis of autism spectrum disorder or major depression;
• history of lifetime psychosis, mania, or seizure disorder;
• baseline suicidality;
• history of seizure disorder or head injury with loss of consciousness

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): collaborator
• University of California, Los Angeles: lead

Study Sites (2)

University of California, Los Angeles

Los Angeles, California, 90095, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Related Publications (4)

• McGough JJ, Loo SK, Sturm A, Cowen J, Leuchter AF, Cook IA. An eight-week, open-trial, pilot feasibility study of trigeminal nerve stimulation in youth with attention-deficit/hyperactivity disorder. Brain Stimul. 2015 Mar-Apr;8(2):299-304. doi: 10.1016/j.brs.2014.11.013. Epub 2014 Nov 28.

  PMID: 25533244 BACKGROUND

• McGough JJ, Sturm A, Cowen J, Tung K, Salgari GC, Leuchter AF, Cook IA, Sugar CA, Loo SK. Double-Blind, Sham-Controlled, Pilot Study of Trigeminal Nerve Stimulation for Attention-Deficit/Hyperactivity Disorder. J Am Acad Child Adolesc Psychiatry. 2019 Apr;58(4):403-411.e3. doi: 10.1016/j.jaac.2018.11.013. Epub 2019 Jan 28.

  PMID: 30768393 BACKGROUND

• McGough JJ, Loo SK, Cook IA. Reply to "Transcutaneous electric currents to target the peripheral and central nervous system in children with attention deficit hyperactivity disorder". Clin Neurophysiol. 2019 Oct;130(10):2008-2009. doi: 10.1016/j.clinph.2019.07.012. Epub 2019 Jul 23. No abstract available.

  PMID: 31377119 BACKGROUND

• Loo SK, Salgari GC, Ellis A, Cowen J, Dillon A, McGough JJ. Trigeminal Nerve Stimulation for Attention-Deficit/Hyperactivity Disorder: Cognitive and Electroencephalographic Predictors of Treatment Response. J Am Acad Child Adolesc Psychiatry. 2021 Jul;60(7):856-864.e1. doi: 10.1016/j.jaac.2020.09.021. Epub 2020 Oct 15.

  PMID: 33068751 BACKGROUND

MeSH Terms

Conditions

Attention Deficit Disorder with Hyperactivity

Condition Hierarchy (Ancestors)

Attention Deficit and Disruptive Behavior Disorders; Neurodevelopmental Disorders; Mental Disorders

Study Officials

• Sandra K. Loo, Ph.D.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• James J. McGough, M.D.

  University of California, Los Angeles

  PRINCIPAL INVESTIGATOR

• Mark A. Stein, Ph.D.

  Seattle Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blind, sham-controlled
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Psychiatry

Study Record Dates

• First Submitted: May 9, 2022
• First Posted: May 16, 2022
• Study Start: September 1, 2022
• Primary Completion: April 10, 2026
• Study Completion: April 10, 2026
• Last Updated: May 7, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Beginning 3 months and ending 5 years after study publication.
• Access Criteria: External investigators will be able to apply for access via an online query system by submitting their affiliations and details of their proposed research.

Locations

US (2)