Clinical trial NCT05374187: Efficacy of Trigeminal Nerve Stimulation for ADHD
Official title: Efficacy of External Trigeminal Nerve Stimulation for Treatment of ADHD
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Attention-Deficit Hyperactivity Disorder
Keywords: ADHD
Neuromodulation
Trigeminal Nerve Stimulation
Cognition
EEG
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2022-05-16
Enrollment: 280
Sex: ALL
Minimum age (years): 7
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Change in ADHD Rating Scale-5 (ADHD-RS-5)
timeFrame: Baseline, weeks 1, 2, 3, 4, 5, 6, 7, 8, 16, 20
Secondary outcomes:
measure: Clinical Global Impression - Severity (CGI-S)
timeFrame: Baseline, weeks 4, 8, 16, 20
measure: Clinical Global Impression - Improvement (CGI-I)
timeFrame: Weeks 1, 2, 3, 4, 5, 6, 7, 8, 16, 20
measure: Change in Strengths and Weakness of Attention-Deficit/Hyperactivity (SWAN) Rating Scale
timeFrame: Baseline, weeks 1, 2, 3, 4, 5, 6, 7, 8, 16, 20
measure: Change in Conners Short Form - Parent
timeFrame: Baseline, weeks 4, 8
measure: Change in Conners Short Form - Teacher
timeFrame: Baseline, weeks 4, 8
measure: Change in Height
timeFrame: Baseline, weeks 4, 8
measure: Change in Weight
timeFrame: Baseline, weeks 4, 8
measure: Change in Weiss Functional Impairment Rating Scale
timeFrame: Baseline, weeks 4, 8
measure: Change in Child Depression Inventory
timeFrame: Baseline, weeks 4, 8
Other outcomes:
measure: Change in Electroencephalography (EEG)
timeFrame: Baseline, weeks 4, 8, 16
measure: Change in Attention Network Task - Go/NoGo
timeFrame: Baseline, weeks 4, 8
measure: Change in Behavior Rating Inventory of Executive Functioning (BRIEF)
timeFrame: Baseline, weeks 1, 2, 3, 4, 5, 6, 7, 8, 16, 20
measure: Change in Children's Sleep Habits Questionnaire (CSHQ)
timeFrame: Baseline, weeks 1, 2, 3, 4, 5, 6, 7, 8, 16, 20
measure: Change in Happy CaFE
timeFrame: Baseline, weeks 4, 8
Locations:
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: University of California, Los Angeles
name: Sandra K. Loo, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: James J. McGough, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Seattle Children's Hospital
name: Mark A. Stein, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.