Attention-Deficit Hyperactivity Disorder
Conditions
Keywords
ADHD, Neuromodulation, Trigeminal Nerve Stimulation, Cognition, EEG
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.
Interventions
DEVICEActive 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.
DEVICESham 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.
Sponsors
University of California, Los Angeles
National Institute of Mental Health (NIMH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind, sham-controlled
Eligibility
Sex/Gender
ALL
Age
7 Years to 12 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in ADHD Rating Scale-5 (ADHD-RS-5) | Baseline, weeks 1, 2, 3, 4, 5, 6, 7, 8, 16, 20 | A dimensional rating of ADHD symptoms, with scores ranging from 0-54, and higher scores indicating worse outcomes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression - Severity (CGI-S) | Baseline, weeks 4, 8, 16, 20 | Categorical measure indicating overall degree of clinical severity among patients with similar diagnoses. Minimum score = 1 (Normal); Maximum score = 7 (Among the most extremely ill patients). |
| Clinical Global Impression - Improvement (CGI-I) | Weeks 1, 2, 3, 4, 5, 6, 7, 8, 16, 20 | Categorical measure indicating degree improved or not improved compared with baseline for each treatment group. Minimum score = 1 (very much improved); Maximum score = 7 (very much worse). Results reflect number of participants stratified as "Improved" (CGI-I \<=2) or "Not Improved" (CGI-I \> 2). |
| Change in Strengths and Weakness of Attention-Deficit/Hyperactivity (SWAN) Rating Scale | Baseline, weeks 1, 2, 3, 4, 5, 6, 7, 8, 16, 20 | A dimensional measure of ADHD symptoms measured on a 7-point scale, with scores ranging from -54 to +54, and lower scores indicating worse symptoms. |
| Change in Conners Short Form - Parent | Baseline, weeks 4, 8 | Parent completed dimensional measure of ADHD symptoms, with score range from 0-135, and higher scores indicating more severe symptoms. |
| Change in Conners Short Form - Teacher | Baseline, weeks 4, 8 | Teacher completed dimensional measure of ADHD symptoms, with score range from 0-123, and higher scores indicating more severe symptoms. |
| Change in Height | Baseline, weeks 4, 8 | A dimensional measure assessed in centimeters (cm). |
| Change in Weight | Baseline, weeks 4, 8 | A dimensional measure assessed in kilograms (kg). |
| Change in Weiss Functional Impairment Rating Scale | Baseline, weeks 4, 8 | A dimensional rating scale designed to evaluate the extent to which an individual's ability to function is impaired by emotional or behavioral problems, with scores ranging from 0 to 150, and higher scores signifying worse impairment. |
| Change in Child Depression Inventory | Baseline, weeks 4, 8 | A child completed dimensional rating of depressive symptoms, with scores ranging from 0 to 54, with higher scores indicating greater severity of depressive symptoms. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSandra K. Loo, Ph.D.
University of California, Los Angeles
PRINCIPAL_INVESTIGATORJames J. McGough, M.D.
University of California, Los Angeles
PRINCIPAL_INVESTIGATORMark A. Stein, Ph.D.
Seattle Children's Hospital
Outcome results
None listed