Clinical trial NCT02155608: Trigeminal Nerve Stimulation for ADHD
Official title: Developmental Pilot Study of External Trigeminal Nerve Stimulation for ADHD
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Attention Deficit Hyperactivity Disorder (ADHD)
Keywords: ADHD
neuromodulation
trigeminal nerve stimulation
cognition
Lead sponsor: University of California, Los Angeles
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2014-06-04
Enrollment: 62
Sex: ALL
Minimum age (years): 8
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to develop external Trigeminal Nerve Stimulation (eTNS) as a potential nonmedication treatment for attention-deficit/hyperactivity disorder (ADHD).

Study hypothesis address potential differences over 4 weeks of active vs. sham eTNS treatment on ADHD symptoms, measures of executive function, electroencephalography (EEG) profiles, other dimensional measures of height, weight, mood, anxiety, and sleep, and side effect profiles.

Detailed description: This three-year developmental study is a double-blind randomized trial of active vs. inactive sham eTNS for ADHD, with four weeks acute treatment followed by an additional one week of clinical observation and testing after treatment cessation.

The study will enroll 85-90 participants aged 8-12 years to achieve a completion target of N=36 for each study condition (total final N = 72). Participants will meet Diagnostic and Statistical Manual-5 (DSM-5) criteria for ADHD, any current presentation, as established by the Behavior Disorders Module of the Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS-PL) and clinical interview.

Other screening procedures include measures of ADHD symptom severity, other behavioral ratings, and cognitive assessments. Once inclusion/exclusion criteria have been reviewed and verified, participants in Phase 1A will have a pre-treatment visit to establish behavioral and cognitive baseline ratings and to obtain an EEG. Participants and parents will be instructed in the use of eTNS, and participants will begin use of the eTNS as directed during sleep each night. Participants will be randomized 1:1 to active or inactive sham eTNS. Participants, families, and most of the study team will remain blind to treatment assignment. Participants will have weekly assessments over the five-week study to assess behavioral, cognitive, and brain activation change and to monitor safety, tolerability, and compliance. Weekly ratings will be obtained from a parent, teacher, and clinician investigator. EEG will occur at baseline, end of treatment (week 4).

In Phase 1B, all participants remain blinded for one week after cessation of the intervention and return for a final visit to assess residual effects of eTNS therapy vs. sham.

Eligibility criteria: Inclusion Criteria:

* male and female children ages 8 to 12 years with DSM-5 ADHD, any current presentation, as determined by KSADS and clinical interview
* minimum scores of 12 on both the inattentive and hyperactive/impulsive subscales of the baseline ADHD-RS
* CGI-S score at baseline ≥ 4
* no current medication with CNS effects
* parents able and willing to monitor proper use of the stimulation device and complete all required rating scales
* estimated Full Scale IQ ≥ 85 based on WASI subtests
* parent and participant able to complete rating scales and other measures in English
* able to cooperate during EEG

Exclusion Criteria:

* 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, seizure disorder or head injury with loss of consciousness
* baseline suicidality

Primary outcomes:
measure: ADHD-IV Rating Scale (ADHD-RS)
timeFrame: Change over baseline and weeks 1, 2, 3, 4 and 5.
Secondary outcomes:
measure: Clinical Global Impression - Improvement (CGI-I)
timeFrame: Change over weeks 1, 2, 3, 4, and 5 compared with baseline.
measure: Conners Global Index - Parent Report
timeFrame: Change over baseline and weeks 1, 2, 3, 4, 5.
measure: Affective Reactivity Index (ARI) - Child
timeFrame: Change over baseline and weeks 4 and 5.
measure: Affective Reactivity Index (ARI) - Parent Report
timeFrame: Change over baseline and weeks 4 and 5.
measure: Multidimensional Anxiety Scale for Children (MASC) - Child Report
timeFrame: Change over baseline and weeks 4 and 5.
measure: Multidimensional Anxiety Scale for Children (MASC) - Parent Report
timeFrame: Change over baseline and weeks 4 and 5.
measure: Height
timeFrame: Change over baseline and weeks 1, 4, and 5.
measure: Weight
timeFrame: Change over baseline and weeks 1, 4, and 5.
measure: Systolic Blood Pressure
timeFrame: Change over baseline and weeks 1, 4, and 5.
measure: Diastolic Blood Pressure
timeFrame: Change over baseline and weeks 1, 4, and 5.
measure: Pulse
timeFrame: Change over baseline and weeks weeks 1, 4, and 5.
measure: Children's Depression Inventory (CDI)
timeFrame: Change over baseline and weeks 4 and 5.
measure: Conners Global Index - Teacher
timeFrame: Change over baseline and weeks 1, 2, 3, 4, 5.
Other outcomes:
measure: Affective Posner Task
timeFrame: Baseline, and Weeks 1 and 4
measure: Attention Network Task (ANT) Response Inhibition
timeFrame: Baseline, Weeks 1 and 4
measure: Spatial Working Memory (SWM)
timeFrame: Baseline, Weeks 1 and 4
measure: Electroencephalography (EEG)
timeFrame: Baseline and Week 4
measure: Behavior Rating Inventory of Executive Functioning (BRIEF)
timeFrame: Baseline, end of Weeks 4 and 5.
measure: Children's Sleep Habits Questionnaire (CSHQ)
timeFrame: Weekly for double-blind trial.
Locations:
city: Los Angeles
country: United States
facility: UCLA Semel Institute
state: California
Study officials:
affiliation: University of California, Los Angeles
name: James J McGough, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of California, Los Angeles
name: Sandra K Loo, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
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: 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.