Efficacy of Trigeminal Nerve Stimulation for ADHD

University of California, Los Angeles (UCLA)

Status: Enrolling

Conditions: Attention-Deficit Hyperactivity Disorder

Treatments: Device: Active eTNS; Device: Sham eTNS

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05374187

1R01MH126041-01A1 (U.S. NIH Grant/Contract)

NIHM R01 MH126041-01A1

Details and patient eligibility

About

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.

Full 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.

Enrollment: 280 estimated patients

Sex: All

Ages: 7 to 12 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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280 participants in 2 patient groups

Active eTNS

Experimental group

Description:

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.

Treatment:

Device: Active eTNS

Sham eTNS

Sham Comparator group

Description:

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.

Treatment:

Device: Sham eTNS

Device: Active eTNS