Trigeminal Nerve Stimulation for ADHD

Attention Deficit Hyperactivity Disorder (ADHD) Clinical Trial

— TNS for ADHD  

Official title:

Developmental Pilot Study of External Trigeminal Nerve Stimulation for ADHD

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02155608
• Other study ID #: NIMH R34MH101282
• Secondary ID: R34MH101282
• Status: Completed
• Phase: N/A
• Start date: April 1, 2015
• Est. completion date: May 30, 2018

Study information

• Verified date: June 2019
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 62
• Est. completion date: May 30, 2018
• Est. primary completion date: May 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 8 Years to 12 Years

Eligibility

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

Related Conditions & MeSH terms

• Attention Deficit Disorder with Hyperactivity
• Attention Deficit Hyperactivity Disorder (ADHD)

Intervention

Device:
• Active eTNS
Participants will receive active trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep for 4 weeks, followed by one week of observation and followup while remaining blinded following treatment discontinuation. Participant deemed to be positive responders to blinded active treatment will be invited to continue open eTNS in a 12 month extension period.
• Sham eTNS
Participants will receive sham trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep for 4 weeks, followed by one week of observation and followup while remaining blinded following treatment discontinuation. At the conclusion of the blinded trial, participants randomized to the sham group will be offered 4 weeks of open eTNS treatment. Participants deemed to be positive responders to open treatment will be invited to continue open nightly eTNS in a 12 month extension period.

Locations

Country	Name	City	State
United States	UCLA Semel Institute	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Affective Posner Task	A laboratory measure of frustration tolerance.	Baseline, and Weeks 1 and 4
Other	Attention Network Task (ANT) Response Inhibition	A computer-administered laboratory measure of executive function.	Baseline, Weeks 1 and 4
Other	Spatial Working Memory (SWM)	A computer-administered laboratory measure of executive function.	Baseline, Weeks 1 and 4
Other	Electroencephalography (EEG)	A laboratory measure of cortical activity.	Baseline and Week 4
Other	Behavior Rating Inventory of Executive Functioning (BRIEF)	A parent completed rating of child executive function. Comprises 5 sub scales that measure various measures of behavior and cognition. Raw scores on each measure are converted to T scores ranging from 28 to 103, with higher scores indicating greater difficulties.	Baseline, end of Weeks 4 and 5.
Other	Children's Sleep Habits Questionnaire (CSHQ)	A parent completed 33-item scale to assess sleep related problems. Total scores range from 33 to 99 divided among 8 sub scales , with higher scores indicating more severe difficulties.	Weekly for double-blind trial.
Primary	ADHD-IV Rating Scale (ADHD-RS)	A dimensional rating of ADHD symptoms, with scores ranging from 0 - 54, and higher scores indicating greater symptom severity.	Change over baseline and weeks 1, 2, 3, 4 and 5.
Secondary	Clinical Global Impression - Improvement (CGI-I)	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 over weeks 1, 2, 3, 4, and 5 compared with baseline.
Secondary	Conners Global Index - Parent Report	Parent completed dimensional measure of ADHD symptoms, with score range from 0- 30, and higher scores indicating more severe symptoms.	Change over baseline and weeks 1, 2, 3, 4, 5.
Secondary	Affective Reactivity Index (ARI) - Child	A child completed dimensional measure of emotional reactivity, with scores ranging from 0-12, and higher scores indicating greater severity.	Change over baseline and weeks 4 and 5.
Secondary	Affective Reactivity Index (ARI) - Parent Report	A parent completed dimensional measure of emotional reactivity, with scores ranging from 0-12, and higher scores indicating greater severity.	Change over baseline and weeks 4 and 5.
Secondary	Multidimensional Anxiety Scale for Children (MASC) - Child Report	A child completed rating of child anxiety, with scores ranging from 0-300, and higher scores indicating greater severity.	Change over baseline and weeks 4 and 5.
Secondary	Multidimensional Anxiety Scale for Children (MASC) - Parent Report	A parent completed rating of child anxiety, with scores ranging from 0-300, and higher scores indicating greater severity.	Change over baseline and weeks 4 and 5.
Secondary	Height	A dimensional measure assessed in centimeters (cm).	Change over baseline and weeks 1, 4, and 5.
Secondary	Weight	A dimensional measure assessed in kilograms (kg).	Change over baseline and weeks 1, 4, and 5.
Secondary	Systolic Blood Pressure	A dimensional measure expressed in mm mercury (Hg).	Change over baseline and weeks 1, 4, and 5.
Secondary	Diastolic Blood Pressure	A dimensional measure assessed in mm mercury (Hg).	Change over baseline and weeks 1, 4, and 5.
Secondary	Pulse	Heart rate in beats per minute (bpm).	Change over baseline and weeks weeks 1, 4, and 5.
Secondary	Children's Depression Inventory (CDI)	A child completed self-report dimensional measure of depressive symptoms, with range of scores from 0 to 54. Higher scores reflect increasing depression. Cutoff scores < 17 to 20 are generally considered to be in the normative range. A score of 36 or higher reflects a relatively severe depression.	Change over baseline and weeks 4 and 5.
Secondary	Conners Global Index - Teacher	Teacher completed dimensional measure of ADHD symptoms, with scores ranging from 0-30, and higher scores indicating more severe symptoms.	Change over baseline and weeks 1, 2, 3, 4, 5.

External Links

•   Pub Med Abstract