Efficacy of Trigeminal Nerve Stimulation for ADHD

NCT ID: NCT05374187

Last Updated: 2025-05-13

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 280 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-09-01
• Study Completion Date: 2026-01-31

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.

Detailed Description

Trigeminal Nerve Stimulation (TNS), an FDA-approved, non-invasive minimal risk intervention approved for treatment of Attention-Deficit/Hyperactivity Disorder (ADHD), administers a low amount of electrical stimulus to the forehead during sleep and is shown to increase activity in brain regions associated with attention and impulse control.

The current study seeks to replicate previous efficacy and safety findings of TNS in a larger, multisite group of ADHD-diagnosed youth, ages 7-12. The study will be conducted at UCLA and Seattle Children's Hospital.

The study comprises 3 phases, with subsequent 12-month follow-up for participants who demonstrate positive response to active therapy. We will screen up to 280 participants to yield an overall study N=225 completers meeting Diagnostic and Statistical Manual-5 (DSM-5) ADHD criteria across the two sites.

Phase 1 is a 4-week double-blind, controlled trial of active vs. sham TNS. Once inclusion/exclusion criteria are assessed, eligible participants have an initial baseline assessment comprised of behavioral ratings, cognitive assessments, and electroencephalography (EEG), and are subsequently randomized 2:1 to active vs. sham treatment. Participants will begin use of TNS as directed each night during sleep for 4 weeks. Participants, families, and most of the study team will remain blind to treatment assignment. Weekly behavioral rating will be obtained from parents, teacher, and clinical investigators. EEG, along with other cognitive measures, will be repeated at week 4.

In Phase 2, participants initially randomized to sham will receive active TNS for an additional 4 weeks, with continued weekly assessments. Phase 3 entails brief naturalistic follow-ups via phone or Zoom at months 3 and 6 post-treatment.

Conditions

Attention-Deficit Hyperactivity Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active eTNS

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.

Group Type: EXPERIMENTAL

Active eTNS

Intervention Type: 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.

Sham eTNS

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.

Group Type: SHAM_COMPARATOR

Active eTNS

Intervention Type: 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.

Sham eTNS

Intervention Type: 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.

Interventions

Active eTNS

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.

Intervention Type: DEVICE

Sham eTNS

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.

Intervention Type: DEVICE

Other Intervention Names

Trigeminal Nerve Stimulation; Monarch eTNS SystemTM (NeuroSigma, Inc., Los Angeles, CA

Eligibility Criteria

Inclusion Criteria

1. 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;

2. total score >= 24 on baseline ADHD-RS;

3. CGI-S score at baseline >= 4;

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;

5. parents able and willing to monitor proper use of the stimulation device and complete all required rating scales;

6. estimated Full Scale IQ >= 80 based on WASI subtests;

7. parent and participant able to complete rating scales and other measures in English;

8. able to cooperate during EEG

Exclusion Criteria

1. impaired functioning to a degree that requires immediate initiation of ADHD medication in the opinion of the parents and/or investigator;

2. current diagnosis of autism spectrum disorder or major depression;

3. history of lifetime psychosis, mania, or seizure disorder;

4. baseline suicidality;

5. history of seizure disorder or head injury with loss of consciousness

• Minimum Eligible Age: 7 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

James McGough

Professor of Clinical Psychiatry

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sandra K. Loo, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

James J. McGough, M.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Mark A. Stein, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Seattle Children's Hospital

Locations

University of California, Los Angeles

Los Angeles, California, United States

Site Status: RECRUITING

Seattle Children's Hospital

Seattle, Washington, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Andrea Dillon, Ph.D.

Role: CONTACT

andreadillon@mednet.ucla.edu

(310) 825-3757

Facility Contacts

Andrea Dillon, Ph.D.

Role: primary

andreadillon@mednet.ucla.edu

(310) 825-3757

Joanna Yuan, Ph.D.

Role: primary

joanna.yuan@seattlechildrens.org

206-884-1761

References

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.

Reference Type: BACKGROUND

PMID: 25533244 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 30768393 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 31377119 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 33068751 (View on PubMed)

Other Identifiers

1R01MH126041-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

NIHM R01 MH126041-01A1

Identifier Type: -

Identifier Source: org_study_id