Attention Deficit Hyperactivity Disorder (ADHD)
Conditions
Keywords
ADHD, neuromodulation, trigeminal nerve stimulation
Brief summary
The purpose of this study will be to offer children previously randomized to sham treatment in a 5-week double-blind sham controlled study of Trigeminal Nerve Stimulation for ADHD (NCT02155608) an opportunity to receive 4-weeks active TNS treatment.
Detailed description
This study will enroll participants with ADHD who previously participated in a 5-week sham-controlled investigation of Trigeminal Nerve Stimulation as a treatment for ADHD, and who were randomized to the sham condition. In the double-blind trial (NCT02155608), children ages 8-12 years undergo study screening and if eligible begin 4 weeks nightly treatment with active or sham TNS administered nightly during sleep. At the conclusion of the 4-week trial, all interventions (both active and sham TNS) are discontinued with blinding remaining in place for an additional week to assess possible residual treatment effects. Participants' randomized condition is unblinded at Week 5. All participants randomized to sham in the double-blind trial are invited to participate in a 4-week open-trial of TNS to allow all participants the opportunity to benefit from the active intervention. During this 4-week open-extension trial, interested participants will receive nightly active TNS during sleep. The final study visit (Visit 5) of the double-blind study will serve as baseline for this open-extension. Participants will return for clinic assessments at Weeks 2 and 4. Participants who achieve clinically significant improvement from active TNS over the 4-week open trial will be invited to receive a year of nightly active-TNS therapy as part of a 12-month extension study.
Interventions
DEVICEActive TNS
Participants will receive 4-weeks nightly treatment with active TNS. Positive responders will be invited to participate in 12-month open-extension study.
Sponsors
National Institute of Mental Health (NIMH)
University of California, Los Angeles
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
8 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
* male and female children ages 8-12 with DSM-5 ADHD, and current presentation, as determined by KSADS and clinical interview * participated in a previous randomized, double-blind, sham-controlled trial of TNS for ADHD, and randomized to the sham condition. * 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
* currently requiring any medication with CNS effects
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ADHD-IV Rating Scale (ADHD-RS) | Change over Baseline, Week 2, Week 4. | A dimensional rating of ADHD symptoms, with scores ranging from 0 to 54, with higher scores signifying worse severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pulse | Change over Baseline, Week 2, Week 4 | A dimensional measure assessed in heart beats per minute. |
| Diastolic Blood Pressure | Change over Baseline, Week 2, Week 4 | A dimensional measure assessed in mm HG. |
| Weight | Change over Baseline, Week 2, Week 4 | A dimensional measure assessed in kg. |
| Systolic Blood Pressure | Change over Baseline, Week 2, Week 4 | A dimensional measure assessed in mm HG. |
| Clinical Global Impression - Improvement (CGI-I) | Change over Baseline, Week 2, Week 4 | 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. |
| Height | Change over Baseline, Week 2, Week 4 | A dimensional measure assessed in cm. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Multidimensional Anxiety Scale for Children (MASC) - Parent Report | Change over Baseline and Week 4 | A parent-completed rating of child anxiety, with scores ranging from 0-300, and higher scores indicating greater severity. |
| Children's Depression Rating Scale - Revised (CDRS-R) | Change over Baseline and Week 4 | A clinician-completed dimensional measure of childhood 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 defines remission. |
| Behavior Rating Inventor of Executive Functioning (BRIEF) | Change over Baseline and weekly during 4-week trial | 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. |
| Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline and weekly during 4-week trial | standard instrument to assess potential suicidality with dichotomous scores (0 = absent; 1 = present) to rate various components of suicidal ideation and behavior. Data derived are summarized under Adverse Event Reporting. |
| Affective Reactivity Index (ARI-C) Child | Change over Baseline, Week 4 | A child-completed dimensional measure of emotional reactivity,with scores ranging from 0-12, and higher scores indicating greater severity. |
| Conners Global Index - Parent Report | Change over Baseline and weekly for 4-week trial | Parent completed dimensional rating of ADHD symptoms,with score range from 0- 30, and higher scores indicating more severe symptoms. |
| Conners Global Index - Teacher Report | Change over Baseline and weekly for 4-week trial | Teacher completed dimensional rating of ADHD symptoms,with scores ranging from 0-30, and higher scores indicating more severe symptoms. |
| Affective Reactivity Index (ARI-P) Parent | Change over Baseline, Week 4 | 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 and weekly for 4-week 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. |
| Multidimensional Anxiety Scale for Children (MASC) - Child Report | Change over Baseline and Week 4 | A child-completed rating of child anxiety, with scores ranging from 0-300, and higher scores indicating greater severity. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Active TNS Participants who previously underwent screening and determination of eligibility in a double-blind sham-controlled trial of TNS for ADHD, and randomized to sham, will be offered upon unblinding at the end of the 5-week controlled trial to receive 4-weeks open treatment with the active TNS condition.
Active TNS: Participants will receive 4-weeks nightly treatment with active TNS. Positive responders will be invited to participate in 12-month open-extension study. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Active TNS |
|---|---|
| ADHD-Rating Scale Total Score | 20.91 score a scale STANDARD_DEVIATION 8.76 |
| Age, Continuous | 10.39 years STANDARD_DEVIATION 1.45 |
| Clinical Global Impression - Severity 3 (Mildly ill) | 2 Participants |
| Clinical Global Impression - Severity 4 (Moderately ill) | 4 Participants |
| Clinical Global Impression - Severity 5 (Markedly ill) | 16 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 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 | 0 Participants |
| Race (NIH/OMB) More than one race | 3 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 | 17 Participants |
| Region of Enrollment United States | 22 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 22 |
| other Total, other adverse events | 14 / 22 |
| serious Total, serious adverse events | 0 / 22 |
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, Week 2, Week 4.
Population: Some participants lost to follow up.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active TNS | ADHD-IV Rating Scale (ADHD-RS) | Baseline | 28.50 score on a scale | Standard Error 1.74 |
| Active TNS | ADHD-IV Rating Scale (ADHD-RS) | Week 2 | 20.91 score on a scale | Standard Error 1.74 |
| Active TNS | ADHD-IV Rating Scale (ADHD-RS) | Week 4 | 18.63 score on a scale | Standard Error 1.85 |
Comparison: Outcomes fitted via a mixed effects model with time as predictor.p-value: <0.0001Mixed 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, Week 2, Week 4
Population: Some participants lost to follow up.
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Active TNS | Clinical Global Impression - Improvement (CGI-I) | Week 2 | Improved | 11 Participants |
| Active TNS | Clinical Global Impression - Improvement (CGI-I) | Week 2 | Not Improved | 11 Participants |
| Active TNS | Clinical Global Impression - Improvement (CGI-I) | Week 4 | Improved | 12 Participants |
| Active TNS | Clinical Global Impression - Improvement (CGI-I) | Week 4 | Not Improved | 8 Participants |
Secondary
Diastolic Blood Pressure
A dimensional measure assessed in mm HG.
Time frame: Change over Baseline, Week 2, Week 4
Population: Some participants lost to follow up.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active TNS | Diastolic Blood Pressure | Baseline | 59.41 mm Hg. | Standard Error 1.91 |
| Active TNS | Diastolic Blood Pressure | Week 2 | 58.36 mm Hg. | Standard Error 1.99 |
| Active TNS | Diastolic Blood Pressure | Week 4 | 60.51 mm Hg. | Standard Error 1.99 |
Comparison: Outcome was fitted using a mixed model with time as predictor.p-value: 0.76Mixed Models Analysis
Secondary
Height
A dimensional measure assessed in cm.
Time frame: Change over Baseline, Week 2, Week 4
Population: Some participants lost to follow up.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active TNS | Height | Baseline | 140.19 cm. | Standard Error 2.02 |
| Active TNS | Height | Week 2 | 140.49 cm. | Standard Error 2.02 |
| Active TNS | Height | Week 4 | 140.92 cm. | Standard Error 2.02 |
Comparison: Outcome was fitted using a mixed model with time as predictor.p-value: 0.02Mixed Models Analysis
Secondary
Pulse
A dimensional measure assessed in heart beats per minute.
Time frame: Change over Baseline, Week 2, Week 4
Population: Some participants lost to follow up.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active TNS | Pulse | Week 2 | 77.04 heart beats per minute. | Standard Error 2.81 |
| Active TNS | Pulse | Week 4 | 76.11 heart beats per minute. | Standard Error 2.81 |
| Active TNS | Pulse | Baseline | 75.81 heart beats per minute. | Standard Error 2.76 |
Comparison: Outcome was fitted using a mixed model with time as predictor.p-value: 0.8Mixed Models Analysis
Secondary
Systolic Blood Pressure
A dimensional measure assessed in mm HG.
Time frame: Change over Baseline, Week 2, Week 4
Population: Some participants lost to follow up.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active TNS | Systolic Blood Pressure | Baseline | 107.27 mm Hg. | Standard Error 2.22 |
| Active TNS | Systolic Blood Pressure | Week 2 | 109.83 mm Hg. | Standard Error 2.3 |
| Active TNS | Systolic Blood Pressure | Week 4 | 107.78 mm Hg. | Standard Error 2.3 |
Comparison: Outcome was fitted using a mixed model with time as predictor.p-value: 0.67Mixed Models Analysis
Secondary
Weight
A dimensional measure assessed in kg.
Time frame: Change over Baseline, Week 2, Week 4
Population: Some participants lost to follow up.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Active TNS | Weight | Baseline | 34.19 kg. | Standard Error 1.53 |
| Active TNS | Weight | Week 2 | 34.61 kg. | Standard Error 1.53 |
| Active TNS | Weight | Week 3 | 34.91 kg. | Standard Error 1.53 |
Comparison: Outcome was fitted using a mixed model with time as predictor.p-value: 0.0005Mixed 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, Week 4
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, Week 4
Other Pre-specified
Behavior Rating Inventor 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: Change over Baseline and weekly during 4-week trial
Other Pre-specified
Children's Depression Rating Scale - Revised (CDRS-R)
A clinician-completed dimensional measure of childhood 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 defines remission.
Time frame: Change over Baseline and Week 4
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 and weekly for 4-week trial
Other Pre-specified
Columbia-Suicide Severity Rating Scale (C-SSRS)
standard instrument to assess potential suicidality with dichotomous scores (0 = absent; 1 = present) to rate various components of suicidal ideation and behavior. Data derived are summarized under Adverse Event Reporting.
Time frame: Baseline and weekly during 4-week trial
Other Pre-specified
Conners Global Index - Parent Report
Parent completed dimensional rating of ADHD symptoms,with score range from 0- 30, and higher scores indicating more severe symptoms.
Time frame: Change over Baseline and weekly for 4-week trial
Other Pre-specified
Conners 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 and weekly for 4-week trial
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 and Week 4
Other Pre-specified
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 Week 4