Attention Deficit Hyperactivity Disorder (ADHD)
Conditions
Keywords
ADHD, neuromodulation, trigeminal nerve stimulation
Brief summary
Participants who exhibit sufficient ADHD symptom improvement in a prior study of active TNS will be invited to continue in a 12-month extension study, designed to collect additional data on long-term response and tolerability and to provide participants ongoing clinical benefit from treatment.
Detailed description
Children, ages 8-12 years, participated in a 5 week double-blind, sham-controlled study of active Trigeminal Nerve Stimulation (TNS). Participants randomized to sham in the double-blind, were then invited into a 4-week open TNS trial. Participants who met positive response criteria to active TNS, either during the original double-blind study or the open-treatment followup, were invited to continue their TNS treatment in a 12-month open extension phase. Participants who continued in the 12-month extension returned for study visits every 3 months to assess ongoing response and safety/tolerability data. Unless otherwise noted, baseline line assessments in the 12-month extension are taken from the final visit of the preceding active treatment trial, i.e. the visit at which positive response criteria were met.
Interventions
DEVICEActive TNS
Sponsors
National Institute of Mental Health (NIMH)
James McGough
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label active treatment
Eligibility
Sex/Gender
ALL
Age
8 Years to 13 Years
Healthy volunteers
No
Inclusion criteria
* male and female children ages 8-13 with DSM-5 ADHD, and current presentation, as determined by KSADS and clinical interview * received active TNS therapy in a previous trial and demonstrated a CGI-I score \<= 2. * parents able and willing to monitor proper use of the TNS device and complete all required rating scales * parent and participants able to compete study rating scales and other measures in English
Exclusion criteria
* none
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ADHD-IV Rating Scale (ADHD-RS) | Change over baseline, Month 3, Month 6, Month 9, Month 12 | A dimensional rating of ADHD symptoms, with scores ranging from 0 to 54, with higher scores signifying worse severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Height | Change over baseline, Month 3, Month 6, Month 9, Month 12 | A dimensional measure assessed in cm. |
| Weight | Change over baseline, Month 3, Month 6, Month 9, Month 12 | A dimensional measure assessed in kg. |
| Clinical Global Impression - Improvement (CGI-I) | Change over baseline, Month 3, Month 6, Month 9, Month 12 | Categorical measure indicating degree improved or not improved compared with global functioning at baseline in the preceding double-blind trial. The base CGI-I scale is a 7-point measure that requires the investigator to assess how much the condition has improved or worsened compared to baseline prior to initiation of treatment. Ratings are (1) very much improved; (2) much improved; (3) minimally improved; (4) no change; (5) minimally worse; (6) much worse; (7) very much worse. For purposes of analysis, the measure is dichotomized such that scores \<= 2 signify improved and scores \> 2 signify not improved. |
| Diastolic Blood Pressure | Change over baseline, Month 3, Month 6, Month 9, Month 12 | A dimensional measure assessed in mm Hg. |
| Pulse | Change over baseline, Month 3, Month 6, Month 9, Month 12 | A dimensional measure assessed in heart beats per minute. |
| Systolic Blood Pressure | Change over baseline, Month 3, Month 6, Month 9, Month 12 | A dimensional measure assessed in mm Hg. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Children's Depression Rating Scale - Revised (CDRS-R) | Change over baseline, Month 3, Month 6, Month 9, Month 12 | A clinician completed dimensional measure of child mood symptoms, obtained from parent and child interview, with range of scores from 17 to 113, and higher scores indicating more severe depression. A score \>= 40 suggests depression; scores \<=28 define remission. |
| Conners Global Index - Parent Report | Change over baseline, Month 3, Month 6, Month 9, Month 12 | Parent completed dimensional rating of ADHD symptoms, with scores ranging from 0-30, and higher scores signifying more severe symptoms. |
| Behavior Rating Inventory of Executive Functioning (BRIEF) | Change over baseline, Month 3, Month 6, Month 9, Month 12 | A parent completed rating of executive functioning. Comprises 5 sub scales that measure various measures of behavior and cognition. Raw scores for each measure are converted to T scores ranging from 28 to 103, with higher scores indicating greater difficulties. |
| Conner Global Index - Teacher Report | Change over baseline, Month 3, Month 6, Month 9, Month 12 | Teacher completed dimensional rating of ADHD symptoms, with scores ranging from 0-30, and higher scores indicating more severe symptoms. |
| Affective Reactivity Index (ARI-C) Child | Change over baseline, Month 3, Month 6, Month 9, Month 12 | A child completed dimensional measure of emotional reactivity, with scores ranging from 0-12, and higher scores indicating greater severity. |
| Affective Reactivity Index (ARI-P) Parent | Change over baseline, Month 3, Month 6, Month 9, Month 12 | A parent completed dimensional measure of emotional reactivity, with scores ranging from 0-12, and higher scores indicating greater severity. |
| Children's Sleep Habits Questionnaire (CSHQ) | Change over baseline, Month 3, Month 6, Month 9, Month 12 | 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. |
| Multidimensional Anxiety Scale for Children (MASC) Child Report | Change over baseline, Month 3, Month 6, Month 9, Month 12 | A child completed rating of child anxiety, with scores ranging from 0-300, and higher scores indicating greater severity. |
| Multidimensional Anxiety Scale for Children (MASC) Parent Report | Change over baseline, Month 3, Month 6, Month 9, Month 12 | A parent completed measure of child anxiety, with scores ranging fro 0-300, and higher scores indicating greater severity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active TNS Participants will receive trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep for up to 12 months of this open-extension trial.
Active TNS: | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 15 |
Baseline characteristics
| Characteristic | Active TNS |
|---|---|
| ADHD-Rating Scale Total Score | 16.56 score on a scale. STANDARD_DEVIATION 8.72 |
| Age, Continuous | 10.41 years STANDARD_DEVIATION 1.32 |
| Clinical Global Impression - Severity (CGI-S) 1 (Normal, not at all ill) | 0 Participants |
| Clinical Global Impression - Severity (CGI-S) 2 (Borderline ill) | 0 Participants |
| Clinical Global Impression - Severity (CGI-S) 3 (Mildly ill) | 2 Participants |
| Clinical Global Impression - Severity (CGI-S) 4 (Moderately ill) | 8 Participants |
| Clinical Global Impression - Severity (CGI-S) 5 (Markedly ill) | 8 Participants |
| Clinical Global Impression - Severity (CGI-S) 6 (Severely ill) | 0 Participants |
| Clinical Global Impression - Severity (CGI-S) 7 (Among the most extremely ill) | 0 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 15 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 12 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 18 |
| other Total, other adverse events | 11 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
ADHD-IV Rating Scale (ADHD-RS)
A dimensional rating of ADHD symptoms, with scores ranging from 0 to 54, with higher scores signifying worse severity.
Time frame: Change over baseline, Month 3, Month 6, Month 9, Month 12
Population: Participants lost to follow up over time.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active TNS | ADHD-IV Rating Scale (ADHD-RS) | Month 3 | 16.56 score on a scale | Standard Error 1.78 |
| Active TNS | ADHD-IV Rating Scale (ADHD-RS) | Baseline | 19.06 score on a scale | Standard Error 1.78 |
| Active TNS | ADHD-IV Rating Scale (ADHD-RS) | Month 6 | 17.51 score on a scale | Standard Error 2.45 |
| Active TNS | ADHD-IV Rating Scale (ADHD-RS) | Month 9 | 15.55 score on a scale | Standard Error 2.76 |
| Active TNS | ADHD-IV Rating Scale (ADHD-RS) | Month 12 | 15.97 score on a scale | Standard Error 3.72 |
Comparison: Outcomes fitted via a mixed model with time as a predictor.p-value: 0.2Mixed Models Analysis
Secondary
Clinical Global Impression - Improvement (CGI-I)
Categorical measure indicating degree improved or not improved compared with global functioning at baseline in the preceding double-blind trial. The base CGI-I scale is a 7-point measure that requires the investigator to assess how much the condition has improved or worsened compared to baseline prior to initiation of treatment. Ratings are (1) very much improved; (2) much improved; (3) minimally improved; (4) no change; (5) minimally worse; (6) much worse; (7) very much worse. For purposes of analysis, the measure is dichotomized such that scores \<= 2 signify improved and scores \> 2 signify not improved.
Time frame: Change over baseline, Month 3, Month 6, Month 9, Month 12
Population: Some participants lost to follow up over time.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Active TNS | Clinical Global Impression - Improvement (CGI-I) | Month 3 | Improved | 16 Participants |
| Active TNS | Clinical Global Impression - Improvement (CGI-I) | Month 3 | Not Improved | 2 Participants |
| Active TNS | Clinical Global Impression - Improvement (CGI-I) | Month 6 | Improved | 8 Participants |
| Active TNS | Clinical Global Impression - Improvement (CGI-I) | Month 6 | Not Improved | 0 Participants |
| Active TNS | Clinical Global Impression - Improvement (CGI-I) | Month 9 | Improved | 7 Participants |
| Active TNS | Clinical Global Impression - Improvement (CGI-I) | Month 9 | Not Improved | 0 Participants |
| Active TNS | Clinical Global Impression - Improvement (CGI-I) | Month 12 | Improved | 3 Participants |
| Active TNS | Clinical Global Impression - Improvement (CGI-I) | Month 12 | Not Improved | 0 Participants |
Secondary
Diastolic Blood Pressure
A dimensional measure assessed in mm Hg.
Time frame: Change over baseline, Month 3, Month 6, Month 9, Month 12
Population: Some participants lost to follow up over time.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active TNS | Diastolic Blood Pressure | Baseline | 61.89 mm Hg. | Standard Error 2.1 |
| Active TNS | Diastolic Blood Pressure | Month 3 | 64.33 mm Hg. | Standard Error 2.1 |
| Active TNS | Diastolic Blood Pressure | Month 6 | 63.49 mm Hg. | Standard Error 3.01 |
| Active TNS | Diastolic Blood Pressure | Month 9 | 64.40 mm Hg. | Standard Error 3.42 |
| Active TNS | Diastolic Blood Pressure | Month 12 | 66.40 mm Hg. | Standard Error 4.7 |
Comparison: Outcomes fitted via a mixed model with time as a predictor.p-value: 0.32Mixed Models Analysis
Secondary
Height
A dimensional measure assessed in cm.
Time frame: Change over baseline, Month 3, Month 6, Month 9, Month 12
Population: Some participants lost to follow up over time.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active TNS | Height | Baseline | 140.45 cm. | Standard Error 2.12 |
| Active TNS | Height | Month 3 | 143.09 cm. | Standard Error 2.11 |
| Active TNS | Height | Month 6 | 144.20 cm. | Standard Error 2.25 |
| Active TNS | Height | Month 9 | 147.27 cm. | Standard Error 2.32 |
| Active TNS | Height | Month 12 | 148.37 cm. | Standard Error 2.56 |
Comparison: Outcomes fitted via a mixed model with time as a predictor.p-value: <0.0001Mixed Models Analysis
Secondary
Pulse
A dimensional measure assessed in heart beats per minute.
Time frame: Change over baseline, Month 3, Month 6, Month 9, Month 12
Population: Some participants were lost to follow up over time.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active TNS | Pulse | Baseline | 81.56 Heart beats per minute. | Standard Error 2.82 |
| Active TNS | Pulse | Month 3 | 80.78 Heart beats per minute. | Standard Error 2.82 |
| Active TNS | Pulse | Month 6 | 76.83 Heart beats per minute. | Standard Error 3.64 |
| Active TNS | Pulse | Month 9 | 79.76 Heart beats per minute. | Standard Error 4.02 |
| Active TNS | Pulse | Month 12 | 77.25 Heart beats per minute. | Standard Error 5.23 |
Comparison: Outcomes fitted via a mixed model with time as a predictor.p-value: 0.27Mixed Models Analysis
Secondary
Systolic Blood Pressure
A dimensional measure assessed in mm Hg.
Time frame: Change over baseline, Month 3, Month 6, Month 9, Month 12
Population: Some participants lost to follow up over time.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active TNS | Systolic Blood Pressure | Baseline | 109.06 mm Hg. | Standard Error 2.47 |
| Active TNS | Systolic Blood Pressure | Month 3 | 108.72 mm Hg. | Standard Error 2.47 |
| Active TNS | Systolic Blood Pressure | Month 6 | 110.06 mm Hg. | Standard Error 3.5 |
| Active TNS | Systolic Blood Pressure | Month 9 | 109.79 mm Hg. | Standard Error 3.97 |
| Active TNS | Systolic Blood Pressure | Month 12 | 102.18 mm Hg. | Standard Error 5.42 |
Comparison: Outcomes fitted via a mixed model with time as a predictor.p-value: 0.6Mixed Models Analysis
Secondary
Weight
A dimensional measure assessed in kg.
Time frame: Change over baseline, Month 3, Month 6, Month 9, Month 12
Population: Some participants lost to follow up over time.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active TNS | Weight | Baseline | 38.42 kg. | Standard Error 3.2 |
| Active TNS | Weight | Month 3 | 38.76 kg. | Standard Error 3.2 |
| Active TNS | Weight | Month 6 | 39.37 kg. | Standard Error 3.22 |
| Active TNS | Weight | Month 9 | 39.96 kg. | Standard Error 3.23 |
| Active TNS | Weight | Moth 12 | 41.82 kg. | Standard Error 3.28 |
Comparison: Outcomes fitted via a mixed model with time as a predictor.p-value: 0.0004Mixed Models Analysis
Other Pre-specified
Affective Reactivity Index (ARI-C) 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, Month 3, Month 6, Month 9, Month 12
Other Pre-specified
Affective Reactivity Index (ARI-P) Parent
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, Month 3, Month 6, Month 9, Month 12
Other Pre-specified
Behavior Rating Inventory of Executive Functioning (BRIEF)
A parent completed rating of executive functioning. Comprises 5 sub scales that measure various measures of behavior and cognition. Raw scores for each measure are converted to T scores ranging from 28 to 103, with higher scores indicating greater difficulties.
Time frame: Change over baseline, Month 3, Month 6, Month 9, Month 12
Other Pre-specified
Children's Depression Rating Scale - Revised (CDRS-R)
A clinician completed dimensional measure of child mood symptoms, obtained from parent and child interview, with range of scores from 17 to 113, and higher scores indicating more severe depression. A score \>= 40 suggests depression; scores \<=28 define remission.
Time frame: Change over baseline, Month 3, Month 6, Month 9, Month 12
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: Change over baseline, Month 3, Month 6, Month 9, Month 12
Other Pre-specified
Conner Global Index - Teacher Report
Teacher completed dimensional rating of ADHD symptoms, with scores ranging from 0-30, and higher scores indicating more severe symptoms.
Time frame: Change over baseline, Month 3, Month 6, Month 9, Month 12
Other Pre-specified
Conners Global Index - Parent Report
Parent completed dimensional rating of ADHD symptoms, with scores ranging from 0-30, and higher scores signifying more severe symptoms.
Time frame: Change over baseline, Month 3, Month 6, Month 9, Month 12
Other Pre-specified
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, Month 3, Month 6, Month 9, Month 12
Other Pre-specified
Multidimensional Anxiety Scale for Children (MASC) Parent Report
A parent completed measure of child anxiety, with scores ranging fro 0-300, and higher scores indicating greater severity.
Time frame: Change over baseline, Month 3, Month 6, Month 9, Month 12