Attention Deficit Hyperactivity Disorder (ADHD)
Conditions
Keywords
ADHD, neuromodulation, trigeminal nerve stimulation, cognition
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.
Interventions
DEVICEActive 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.
DEVICESham 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.
Sponsors
National Institute of Mental Health (NIMH)
University of California, Los Angeles
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
8 Years to 12 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ADHD-IV Rating Scale (ADHD-RS) | Change over baseline and weeks 1, 2, 3, 4 and 5. | A dimensional rating of ADHD symptoms, with scores ranging from 0 - 54, and higher scores indicating greater symptom severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Multidimensional Anxiety Scale for Children (MASC) - Child Report | Change over baseline and weeks 4 and 5. | A child completed rating of child anxiety, with scores ranging from 0-300, and higher scores indicating greater severity. |
| Weight | Change over baseline and weeks 1, 4, and 5. | A dimensional measure assessed in kilograms (kg). |
| Systolic Blood Pressure | Change over baseline and weeks 1, 4, and 5. | A dimensional measure expressed in mm mercury (Hg). |
| Diastolic Blood Pressure | Change over baseline and weeks 1, 4, and 5. | A dimensional measure assessed in mm mercury (Hg). |
| Pulse | Change over baseline and weeks weeks 1, 4, and 5. | Heart rate in beats per minute (bpm). |
| Children's Depression Inventory (CDI) | Change over baseline and weeks 4 and 5. | 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. |
| Conners Global Index - Teacher | Change over baseline and weeks 1, 2, 3, 4, 5. | Teacher completed dimensional measure of ADHD symptoms, with scores ranging from 0-30, and higher scores indicating more severe symptoms. |
| Clinical Global Impression - Improvement (CGI-I) | Change over weeks 1, 2, 3, 4, and 5 compared with baseline. | 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). |
| Conners Global Index - Parent Report | Change over baseline and weeks 1, 2, 3, 4, 5. | Parent completed dimensional measure of ADHD symptoms, with score range from 0- 30, and higher scores indicating more severe symptoms. |
| Affective Reactivity Index (ARI) - Child | Change over baseline and weeks 4 and 5. | A child completed dimensional measure of emotional reactivity, with scores ranging from 0-12, and higher scores indicating greater severity. |
| Affective Reactivity Index (ARI) - Parent Report | Change over baseline and weeks 4 and 5. | A parent completed dimensional measure of emotional reactivity, with scores ranging from 0-12, and higher scores indicating greater severity. |
| Multidimensional Anxiety Scale for Children (MASC) - Parent Report | Change over baseline and weeks 4 and 5. | A parent completed rating of child anxiety, with scores ranging from 0-300, and higher scores indicating greater severity. |
| Height | Change over baseline and weeks 1, 4, and 5. | A dimensional measure assessed in centimeters (cm). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Spatial Working Memory (SWM) | Baseline, Weeks 1 and 4 | A computer-administered laboratory measure of executive function. |
| Electroencephalography (EEG) | Baseline and Week 4 | A laboratory measure of cortical activity. |
| Behavior Rating Inventory of Executive Functioning (BRIEF) | Baseline, end of Weeks 4 and 5. | 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. |
| Children's Sleep Habits Questionnaire (CSHQ) | Weekly for double-blind trial. | 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. |
| Affective Posner Task | Baseline, and Weeks 1 and 4 | A laboratory measure of frustration tolerance. |
| Attention Network Task (ANT) Response Inhibition | Baseline, Weeks 1 and 4 | A computer-administered laboratory measure of executive function. |
Countries
United States
Participant flow
Recruitment details
Participants enrolled between 04/2015 and 03/2017. Participants were recruited through community advertisements and internet postings.
Pre-assignment details
Potential participants underwent screening and those eligible returned for baseline assessment and randomization. Of 79 individuals screened, 64 met inclusion/exclusion criteria for participation. Two of these chose not to return after screening, most likely because they were only interested in ADHD assessment.
Participants by arm
| Arm | Count |
|---|---|
| Active eTNS Following screening and determination of eligibility, participants at baseline are randomized to receive 4 weeks nightly treatment with active or sham eTNS, followed by one week ongoing blinded assessment following treatment discontinuation.
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. | 32 |
| Sham eTNS Following screening and determination of eligibility, participants at baseline are randomized to receive 4 weeks nightly treatment with active or sham eTNS, followed by one week ongoing blinded assessment following treatment discontinuation.
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. | 30 |
| Total | 62 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| 1a: 4 Week Double Blind Sham Controlled | Lost to Follow-up | 0 | 1 |
| 1b: 1 Week Blinded Post Treatment | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | Total | Active eTNS | Sham eTNS |
|---|---|---|---|
| ADHD-Rating Scale Total Score | 32.47 units on a scale STANDARD_DEVIATION 6.21 | 32.13 units on a scale STANDARD_DEVIATION 6.28 | 32.83 units on a scale STANDARD_DEVIATION 6.22 |
| ADHD Subtype Combined | 39 Participants | 22 Participants | 17 Participants |
| ADHD Subtype Hyperactive/Impulsive | 2 Participants | 1 Participants | 1 Participants |
| ADHD Subtype Inattentive | 21 Participants | 9 Participants | 12 Participants |
| Age, Continuous | 10.40 years STANDARD_DEVIATION 1.4 | 10.26 years STANDARD_DEVIATION 1.39 | 10.50 years STANDARD_DEVIATION 1.37 |
| Clinical Global Impression - Severity 4 (Moderately iIl) | 21 Participants | 10 Participants | 11 Participants |
| Clinical Global Impression - Severity 5 (Markedly ill) | 41 Participants | 22 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 5 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 52 Participants | 27 Participants | 25 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Full Scale IQ Estimate | 108.9 IQ points STANDARD_DEVIATION 13.2 | 110.4 IQ points STANDARD_DEVIATION 12.3 | 107.3 IQ points STANDARD_DEVIATION 14.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 5 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 8 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 40 Participants | 20 Participants | 20 Participants |
| Sex: Female, Male Female | 40 Participants | 19 Participants | 21 Participants |
| Sex: Female, Male Male | 22 Participants | 13 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 30 |
| other Total, other adverse events | 23 / 32 | 22 / 30 |
| serious Total, serious adverse events | 0 / 32 | 0 / 30 |
Outcome results
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.
Time frame: Change over baseline and weeks 1, 2, 3, 4 and 5.
Population: Data missing for some visits.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | ADHD-IV Rating Scale (ADHD-RS) | Week 1 | 26.16 score on a scale | Standard Error 1.39 |
| Active eTNS | ADHD-IV Rating Scale (ADHD-RS) | Week 3 | 23.92 score on a scale | Standard Error 1.42 |
| Active eTNS | ADHD-IV Rating Scale (ADHD-RS) | Baseline | 32.12 score on a scale | Standard Error 1.39 |
| Active eTNS | ADHD-IV Rating Scale (ADHD-RS) | Week 4 | 23.38 score on a scale | Standard Error 1.4 |
| Active eTNS | ADHD-IV Rating Scale (ADHD-RS) | Week 5 | 25.5 score on a scale | Standard Error 1.4 |
| Active eTNS | ADHD-IV Rating Scale (ADHD-RS) | Week 2 | 24.74 score on a scale | Standard Error 1.4 |
| Sham eTNS | ADHD-IV Rating Scale (ADHD-RS) | Week 5 | 29.1 score on a scale | Standard Error 1.47 |
| Sham eTNS | ADHD-IV Rating Scale (ADHD-RS) | Baseline | 32.83 score on a scale | Standard Error 1.43 |
| Sham eTNS | ADHD-IV Rating Scale (ADHD-RS) | Week 1 | 28.53 score on a scale | Standard Error 1.43 |
| Sham eTNS | ADHD-IV Rating Scale (ADHD-RS) | Week 2 | 28.31 score on a scale | Standard Error 1.48 |
| Sham eTNS | ADHD-IV Rating Scale (ADHD-RS) | Week 3 | 28.78 score on a scale | Standard Error 1.5 |
| Sham eTNS | ADHD-IV Rating Scale (ADHD-RS) | Week 4 | 27.50 score on a scale | Standard Error 1.46 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group-by-time interactions to test for treatment effects using a piecewise linear time trend. This was parameterized in the model as a standard linear variable, time (ranging from baseline to 4 weeks) and a second variable, time2, defined as 0 at baseline and time past week 1 for subsequent weeks. The time2 coefficient represents the change in slope after the initial week.p-value: 0.54Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group-by-time interactions to test for treatment effects using a piecewise linear time trend. This was parameterized in the model as a standard linear variable, time (ranging from baseline to 4 weeks) and a second variable, time2, defined as 0 at baseline and time past week 1 for subsequent weeks. The time2 coefficient represents the change in slope after the initial week.p-value: <0.0001Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group-by-time interactions to test for treatment effects using a piecewise linear time trend. This was parameterized in the model as a standard linear variable, time (ranging from baseline to 4 weeks) and a second variable, time2, defined as 0 at baseline and time past week 1 for subsequent weeks. The time2 coefficient represents the change in slope after the initial week.p-value: 0.005Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group-by-time interactions to test for treatment effects using a piecewise linear time trend. This was parameterized in the model as a standard linear variable, time (ranging from baseline to 4 weeks) and a second variable, time2, defined as 0 at baseline and time past week 1 for subsequent weeks. The time2 coefficient represents the change in slope after the initial week.p-value: <0.0001Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.02Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.05Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.73Mixed Models Analysis
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.
Time frame: Change over baseline and weeks 4 and 5.
Population: Data missing for some visits
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | Affective Reactivity Index (ARI) - Child | Baseline | 4.5 score on a scale | Standard Error 0.5 |
| Active eTNS | Affective Reactivity Index (ARI) - Child | Week 4 | 4.1 score on a scale | Standard Error 0.5 |
| Active eTNS | Affective Reactivity Index (ARI) - Child | Week 5 | 3.9 score on a scale | Standard Error 0.5 |
| Sham eTNS | Affective Reactivity Index (ARI) - Child | Baseline | 4.5 score on a scale | Standard Error 0.5 |
| Sham eTNS | Affective Reactivity Index (ARI) - Child | Week 4 | 3.8 score on a scale | Standard Error 0.6 |
| Sham eTNS | Affective Reactivity Index (ARI) - Child | Week 5 | 3.5 score on a scale | Standard Error 0.6 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.91Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.15Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.64Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.66Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.48Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.81Mixed Models Analysis
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.
Time frame: Change over baseline and weeks 4 and 5.
Population: Data missing for some visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | Affective Reactivity Index (ARI) - Parent Report | Baseline | 4.4 score on a scale | Standard Error 0.6 |
| Active eTNS | Affective Reactivity Index (ARI) - Parent Report | Week 4 | 3.6 score on a scale | Standard Error 0.6 |
| Active eTNS | Affective Reactivity Index (ARI) - Parent Report | Week 5 | 3.8 score on a scale | Standard Error 0.7 |
| Sham eTNS | Affective Reactivity Index (ARI) - Parent Report | Baseline | 4.5 score on a scale | Standard Error 0.6 |
| Sham eTNS | Affective Reactivity Index (ARI) - Parent Report | Week 4 | 3.6 score on a scale | Standard Error 0.7 |
| Sham eTNS | Affective Reactivity Index (ARI) - Parent Report | Week 5 | 4.2 score on a scale | Standard Error 0.7 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.89Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.14Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.8Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.93Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.15Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.28Mixed Models Analysis
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.
Time frame: Change over baseline and weeks 4 and 5.
Population: Data missing for some visits.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | Children's Depression Inventory (CDI) | Baseline | 10.14 score on a scale | Standard Error 1.23 |
| Active eTNS | Children's Depression Inventory (CDI) | Week 4 | 8.94 score on a scale | Standard Error 1.22 |
| Active eTNS | Children's Depression Inventory (CDI) | Week 5 | 7.88 score on a scale | Standard Error 1.32 |
| Sham eTNS | Children's Depression Inventory (CDI) | Baseline | 9.10 score on a scale | Standard Error 1.23 |
| Sham eTNS | Children's Depression Inventory (CDI) | Week 4 | 8.21 score on a scale | Standard Error 1.24 |
| Sham eTNS | Children's Depression Inventory (CDI) | Week 5 | 7.34 score on a scale | Standard Error 1.37 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.55Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.34Mixed Models Analysis
Comparison: Phase 1 a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interaction to test for treatment effects.p-value: 0.81Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.83Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.04Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.73Mixed Models Analysis
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).
Time frame: Change over weeks 1, 2, 3, 4, and 5 compared with baseline.
Population: Data missing for some visits.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Active eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 1 | Improved | 8 Participants |
| Active eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 1 | Not Improved | 24 Participants |
| Active eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 2 | Improved | 12 Participants |
| Active eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 2 | Not Improved | 19 Participants |
| Active eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 3 | Improved | 14 Participants |
| Active eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 3 | Not Improved | 16 Participants |
| Active eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 4 | Improved | 16 Participants |
| Active eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 4 | Not Improved | 15 Participants |
| Active eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 5 | Improved | 4 Participants |
| Active eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 5 | Not Improved | 27 Participants |
| Sham eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 4 | Not Improved | 24 Participants |
| Sham eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 1 | Improved | 4 Participants |
| Sham eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 3 | Not Improved | 22 Participants |
| Sham eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 1 | Not Improved | 26 Participants |
| Sham eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 5 | Not Improved | 26 Participants |
| Sham eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 2 | Improved | 4 Participants |
| Sham eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 4 | Improved | 4 Participants |
| Sham eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 2 | Not Improved | 22 Participants |
| Sham eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 5 | Improved | 2 Participants |
| Sham eTNS | Clinical Global Impression - Improvement (CGI-I) | Week 3 | Improved | 3 Participants |
Comparison: Phase 1a: Assessed effects of group and time on categorical measure CGI-I from Baseline through Visit 4.p-value: 0.003Chi-squared
Comparison: Phase 1a: Assessed effects of group and time on categorical measure CGI-I from Baseline through Visit 4.p-value: 0.17Chi-squared
Comparison: Phase 1b: Assessed effects of group on categorical measure CGI-I from at Visit 5 compared to baseline.p-value: 0.46Chi-squared
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.
Time frame: Change over baseline and weeks 1, 2, 3, 4, 5.
Population: Data missing for some visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | Conners Global Index - Parent Report | Baseline | 18.3 score on a scale | Standard Error 1.1 |
| Active eTNS | Conners Global Index - Parent Report | Week 1 | 15.7 score on a scale | Standard Error 1.1 |
| Active eTNS | Conners Global Index - Parent Report | Week 2 | 13.0 score on a scale | Standard Error 1.1 |
| Active eTNS | Conners Global Index - Parent Report | Week 3 | 13.4 score on a scale | Standard Error 1.1 |
| Active eTNS | Conners Global Index - Parent Report | Week 4 | 14.7 score on a scale | Standard Error 14.7 |
| Active eTNS | Conners Global Index - Parent Report | Week 5 | 14.1 score on a scale | Standard Error 1.1 |
| Sham eTNS | Conners Global Index - Parent Report | Week 4 | 14.6 score on a scale | Standard Error 1.2 |
| Sham eTNS | Conners Global Index - Parent Report | Baseline | 17.4 score on a scale | Standard Error 1.1 |
| Sham eTNS | Conners Global Index - Parent Report | Week 3 | 15.2 score on a scale | Standard Error 1.2 |
| Sham eTNS | Conners Global Index - Parent Report | Week 1 | 16.5 score on a scale | Standard Error 1.1 |
| Sham eTNS | Conners Global Index - Parent Report | Week 5 | 15.7 score on a scale | Standard Error 1.2 |
| Sham eTNS | Conners Global Index - Parent Report | Week 2 | 15.2 score on a scale | Standard Error 1.2 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group-by-time interactions to test for treatment effects using a piecewise linear time trend. This was parameterized in the model as a standard linear variable, time (ranging from baseline to 4 weeks) and a second variable, time2, defined as 0 at baseline and time past week 1 for subsequent weeks. The time2 coefficient represents the change in slope after the initial week.p-value: 0.91Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group-by-time interactions to test for treatment effects using a piecewise linear time trend. This was parameterized in the model as a standard linear variable, time (ranging from baseline to 4 weeks) and a second variable, time2, defined as 0 at baseline and time past week 1 for subsequent weeks. The time2 coefficient represents the change in slope after the initial week.p-value: 0.0004Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group-by-time interactions to test for treatment effects using a piecewise linear time trend. This was parameterized in the model as a standard linear variable, time (ranging from baseline to 4 weeks) and a second variable, time2, defined as 0 at baseline and time past week 1 for subsequent weeks. The time2 coefficient represents the change in slope after the initial week.p-value: 0.37Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group-by-time interactions to test for treatment effects using a piecewise linear time trend. This was parameterized in the model as a standard linear variable, time (ranging from baseline to 4 weeks) and a second variable, time2, defined as 0 at baseline and time past week 1 for subsequent weeks. The time2 coefficient represents the change in slope after the initial week.p-value: 0.007Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.67Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.68Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.16Mixed Models Analysis
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.
Time frame: Change over baseline and weeks 1, 2, 3, 4, 5.
Population: Results may not be valid due to problems with data collection leading to substantial missing data.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | Conners Global Index - Teacher | Week 2 | 14.36 score on a scale | Standard Error 1.27 |
| Active eTNS | Conners Global Index - Teacher | Week 3 | 14.56 score on a scale | Standard Error 1.92 |
| Active eTNS | Conners Global Index - Teacher | Week 1 | 15.86 score on a scale | Standard Error 1.23 |
| Active eTNS | Conners Global Index - Teacher | Week 4 | 15.43 score on a scale | Standard Error 1.69 |
| Active eTNS | Conners Global Index - Teacher | Baseline | 15.76 score on a scale | Standard Error 1.32 |
| Active eTNS | Conners Global Index - Teacher | Week 5 | 11.54 score on a scale | Standard Error 3.33 |
| Sham eTNS | Conners Global Index - Teacher | Week 2 | 15.64 score on a scale | Standard Error 1.77 |
| Sham eTNS | Conners Global Index - Teacher | Baseline | 15.15 score on a scale | Standard Error 1.32 |
| Sham eTNS | Conners Global Index - Teacher | Week 1 | 11.37 score on a scale | Standard Error 1.46 |
| Sham eTNS | Conners Global Index - Teacher | Week 5 | 18.83 score on a scale | Standard Error 3.89 |
| Sham eTNS | Conners Global Index - Teacher | Week 3 | 16.56 score on a scale | Standard Error 1.92 |
| Sham eTNS | Conners Global Index - Teacher | Week 4 | 14.53 score on a scale | Standard Error 1.89 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group-by-time interactions to test for treatment effects using a piecewise linear time trend. This was parametrized in the model as a standard linear viable, time (ranging from baseline to 4 weeks) and a second variable, time2. defined as 0 at baseline and time past week 1 for subsequent weeks. The time 2 coefficient represents the change in slope after the initial week.p-value: 0.21Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group-by-time interactions to test for treatment effects using a piecewise linear time trend. This was parametrized in the model as a standard linear viable, time (ranging from baseline to 4 weeks) and a second variable, time2. defined as 0 at baseline and time past week 1 for subsequent weeks. The time 2 coefficient represents the change in slope after the initial week.p-value: 0.39Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group-by-time interactions to test for treatment effects using a piecewise linear time trend. This was parametrized in the model as a standard linear viable, time (ranging from baseline to 4 weeks) and a second variable, time2. defined as 0 at baseline and time past week 1 for subsequent weeks. The time 2 coefficient represents the change in slope after the initial week.p-value: 0.18Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group-by-time interactions to test for treatment effects using a piecewise linear time trend. This was parametrized in the model as a standard linear viable, time (ranging from baseline to 4 weeks) and a second variable, time2. defined as 0 at baseline and time past week 1 for subsequent weeks. The time 2 coefficient represents the change in slope after the initial week.p-value: 0.22Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.21Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 1Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 1Mixed Models Analysis
Secondary
Diastolic Blood Pressure
A dimensional measure assessed in mm mercury (Hg).
Time frame: Change over baseline and weeks 1, 4, and 5.
Population: Data missing for some visits.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | Diastolic Blood Pressure | Baseline | 64.97 mm Hg. | Standard Error 1.66 |
| Active eTNS | Diastolic Blood Pressure | Week 1 | 63.69 mm Hg. | Standard Error 1.66 |
| Active eTNS | Diastolic Blood Pressure | Week 4 | 65.09 mm Hg. | Standard Error 1.66 |
| Active eTNS | Diastolic Blood Pressure | Week 5 | 65.30 mm Hg. | Standard Error 1.76 |
| Sham eTNS | Diastolic Blood Pressure | Week 5 | 60.89 mm Hg. | Standard Error 1.86 |
| Sham eTNS | Diastolic Blood Pressure | Baseline | 63.61 mm Hg. | Standard Error 1.73 |
| Sham eTNS | Diastolic Blood Pressure | Week 4 | 61.01 mm Hg. | Standard Error 1.73 |
| Sham eTNS | Diastolic Blood Pressure | Week 1 | 62.33 mm Hg. | Standard Error 1.71 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.64Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.19Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.22Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.05Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.96Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.92Mixed Models Analysis
Secondary
Height
A dimensional measure assessed in centimeters (cm).
Time frame: Change over baseline and weeks 1, 4, and 5.
Population: Data missing for some visits.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | Height | Baseline | 142.82 cm. | Standard Error 1.78 |
| Active eTNS | Height | Week 1 | 142.79 cm. | Standard Error 1.78 |
| Active eTNS | Height | Week 4 | 143.14 cm. | Standard Error 1.78 |
| Active eTNS | Height | Week 5 | 143.58 cm. | Standard Error 1.81 |
| Sham eTNS | Height | Week 5 | 142.30 cm. | Standard Error 1.9 |
| Sham eTNS | Height | Baseline | 141.45 cm. | Standard Error 1.84 |
| Sham eTNS | Height | Week 4 | 142.31 cm. | Standard Error 1.84 |
| Sham eTNS | Height | Week 1 | 141.57 cm. | Standard Error 1.84 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.29Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.02Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.31Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.69Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.33Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.35Mixed Models Analysis
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.
Time frame: Change over baseline and weeks 4 and 5.
Population: Data missing from some visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | Multidimensional Anxiety Scale for Children (MASC) - Child Report | Baseline | 61.0 score on a scale | Standard Error 4.7 |
| Active eTNS | Multidimensional Anxiety Scale for Children (MASC) - Child Report | Week 4 | 59.5 score on a scale | Standard Error 4.8 |
| Active eTNS | Multidimensional Anxiety Scale for Children (MASC) - Child Report | Week 5 | 56.1 score on a scale | Standard Error 5 |
| Sham eTNS | Multidimensional Anxiety Scale for Children (MASC) - Child Report | Baseline | 61.0 score on a scale | Standard Error 4.9 |
| Sham eTNS | Multidimensional Anxiety Scale for Children (MASC) - Child Report | Week 4 | 56.4 score on a scale | Standard Error 4.7 |
| Sham eTNS | Multidimensional Anxiety Scale for Children (MASC) - Child Report | Week 5 | 52.3 score on a scale | Standard Error 5.3 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.91Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.11Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.4Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.49Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.18Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.72Mixed Models Analysis
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.
Time frame: Change over baseline and weeks 4 and 5.
Population: Data missing for some visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | Multidimensional Anxiety Scale for Children (MASC) - Parent Report | Baseline | 46.2 score on a scale | Standard Error 3 |
| Active eTNS | Multidimensional Anxiety Scale for Children (MASC) - Parent Report | Week 4 | 33.9 score on a scale | Standard Error 3 |
| Active eTNS | Multidimensional Anxiety Scale for Children (MASC) - Parent Report | Week 5 | 32.4 score on a scale | Standard Error 2.9 |
| Sham eTNS | Multidimensional Anxiety Scale for Children (MASC) - Parent Report | Baseline | 48.4 score on a scale | Standard Error 3.1 |
| Sham eTNS | Multidimensional Anxiety Scale for Children (MASC) - Parent Report | Week 4 | 42.9 score on a scale | Standard Error 3.2 |
| Sham eTNS | Multidimensional Anxiety Scale for Children (MASC) - Parent Report | Week 5 | 38.2 score on a scale | Standard Error 3 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.62Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.06Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.09Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.06Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.05Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.42Mixed Models Analysis
Secondary
Pulse
Heart rate in beats per minute (bpm).
Time frame: Change over baseline and weeks weeks 1, 4, and 5.
Population: Data missing for some visits.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | Pulse | Baseline | 76.69 bpm. | Standard Error 2.27 |
| Active eTNS | Pulse | Week 4 | 81.78 bpm. | Standard Error 2.27 |
| Active eTNS | Pulse | Week 5 | 79.42 bpm. | Standard Error 2.1 |
| Active eTNS | Pulse | Week 1 | 79.91 bpm. | Standard Error 2.27 |
| Sham eTNS | Pulse | Week 5 | 78.18 bpm. | Standard Error 2.22 |
| Sham eTNS | Pulse | Baseline | 76.70 bpm. | Standard Error 2.37 |
| Sham eTNS | Pulse | Week 1 | 79.70 bpm. | Standard Error 2.34 |
| Sham eTNS | Pulse | Week 4 | 75.18 bpm. | Standard Error 2.37 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.79Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.3Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.03Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.14Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.82Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.07Mixed Models Analysis
Secondary
Systolic Blood Pressure
A dimensional measure expressed in mm mercury (Hg).
Time frame: Change over baseline and weeks 1, 4, and 5.
Population: Data missing from some visits.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | Systolic Blood Pressure | Baseline | 108.50 mm Hg. | Standard Error 2.26 |
| Active eTNS | Systolic Blood Pressure | Week 1 | 107.03 mm Hg. | Standard Error 2.26 |
| Active eTNS | Systolic Blood Pressure | Week 4 | 111.00 mm Hg. | Standard Error 2.26 |
| Active eTNS | Systolic Blood Pressure | Week 5 | 112.26 mm Hg. | Standard Error 2.02 |
| Sham eTNS | Systolic Blood Pressure | Week 5 | 106.10 mm Hg. | Standard Error 2.13 |
| Sham eTNS | Systolic Blood Pressure | Baseline | 106.10 mm Hg. | Standard Error 2.36 |
| Sham eTNS | Systolic Blood Pressure | Week 4 | 107.79 mm Hg. | Standard Error 2.36 |
| Sham eTNS | Systolic Blood Pressure | Week 1 | 109.20 mm Hg. | Standard Error 2.34 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.94Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.76Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.39Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.09Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.79Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.22Mixed Models Analysis
Secondary
Weight
A dimensional measure assessed in kilograms (kg).
Time frame: Change over baseline and weeks 1, 4, and 5.
Population: Data missing for some visits.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active eTNS | Weight | Baseline | 38.83 kg. | Standard Error 1.88 |
| Active eTNS | Weight | Week 1 | 39.12 kg. | Standard Error 1.88 |
| Active eTNS | Weight | Week 4 | 39.65 kg. | Standard Error 1.88 |
| Active eTNS | Weight | Week 5 | 39.85 kg. | Standard Error 1.93 |
| Sham eTNS | Weight | Week 5 | 35.71 kg. | Standard Error 2.03 |
| Sham eTNS | Weight | Baseline | 35.34 kg. | Standard Error 1.95 |
| Sham eTNS | Weight | Week 4 | 35.67 kg. | Standard Error 1.95 |
| Sham eTNS | Weight | Week 1 | 35.58 kg. | Standard Error 1.95 |
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.21Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.02Mixed Models Analysis
Comparison: Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.p-value: 0.01Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.15Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.05Mixed Models Analysis
Comparison: Phase 1b: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects between visits 4 and 5.p-value: 0.79Mixed Models Analysis
Other Pre-specified
Affective Posner Task
A laboratory measure of frustration tolerance.
Time frame: Baseline, and Weeks 1 and 4
Other Pre-specified
Attention Network Task (ANT) Response Inhibition
A computer-administered laboratory measure of executive function.
Time frame: Baseline, Weeks 1 and 4
Other Pre-specified
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.
Time frame: Baseline, end of Weeks 4 and 5.
Other Pre-specified
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.
Time frame: Weekly for double-blind trial.
Other Pre-specified
Electroencephalography (EEG)
A laboratory measure of cortical activity.
Time frame: Baseline and Week 4
Other Pre-specified
Spatial Working Memory (SWM)
A computer-administered laboratory measure of executive function.
Time frame: Baseline, Weeks 1 and 4