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Trial record 1 of 3 for:    monarch etns
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Trigeminal Nerve Stimulation for ADHD (TNS for ADHD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02155608
Recruitment Status : Completed
First Posted : June 4, 2014
Results First Posted : April 12, 2019
Last Update Posted : July 2, 2019
Sponsor:
Collaborator:
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
James McGough, University of California, Los Angeles

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Attention Deficit Hyperactivity Disorder (ADHD)
Interventions Device: Active eTNS
Device: Sham eTNS
Enrollment 62
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.
Arm/Group Title Active TNS Sham TNS
Hide Arm/Group Description

Active TNS

Active TNS: Participants randomized to active trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep.

Sham TNS

Sham TNS: Participants randomized to sham trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep.

Period Title: 1a: 4 Week Double Blind Sham Controlled
Started 32 30
Completed 32 29
Not Completed 0 1
Reason Not Completed
Lost to Follow-up             0             1
Period Title: 1b: 1 Week Blinded Post Treatment
Started 32 29
Completed 31 28
Not Completed 1 1
Reason Not Completed
Lost to Follow-up             1             1
Arm/Group Title Active eTNS Sham eTNS Total
Hide Arm/Group Description

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.

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.

Total of all reporting groups
Overall Number of Baseline Participants 32 30 62
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 32 participants 30 participants 62 participants
10.26  (1.39) 10.50  (1.37) 10.40  (1.4)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 30 participants 62 participants
Female
19
  59.4%
21
  70.0%
40
  64.5%
Male
13
  40.6%
9
  30.0%
22
  35.5%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 30 participants 62 participants
Hispanic or Latino
5
  15.6%
5
  16.7%
10
  16.1%
Not Hispanic or Latino
27
  84.4%
25
  83.3%
52
  83.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 30 participants 62 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
5
  15.6%
5
  16.7%
10
  16.1%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
4
  12.5%
0
   0.0%
4
   6.5%
White
20
  62.5%
20
  66.7%
40
  64.5%
More than one race
3
   9.4%
5
  16.7%
8
  12.9%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
ADHD Subtype   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 30 participants 62 participants
Combined
22
  68.8%
17
  56.7%
39
  62.9%
Inattentive
9
  28.1%
12
  40.0%
21
  33.9%
Hyperactive/Impulsive
1
   3.1%
1
   3.3%
2
   3.2%
[1]
Measure Description: Subtypes listed (Combined, Inattentive, Hyperactive/Impulsive) reflect different subtypes of ADHD according to diagnostic criteria. They do not reflect any grading or measure of severity.
Full Scale IQ Estimate   [1] 
Mean (Standard Deviation)
Unit of measure:  IQ points
Number Analyzed 32 participants 30 participants 62 participants
110.4  (12.3) 107.3  (14.2) 108.9  (13.2)
[1]
Measure Description: Based on the Wechsler Abbreviated Scales of Intelligence, 3rd Edition.
ADHD-Rating Scale Total Score   [1] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 32 participants 30 participants 62 participants
32.13  (6.28) 32.83  (6.22) 32.47  (6.21)
[1]
Measure Description: A dimensional rating of ADHD symptoms with scores ranging from 0 to 54, with higher scores indicating greater severity.
Clinical Global Impression - Severity   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 32 participants 30 participants 62 participants
4 (Moderately iIl)
10
  31.3%
11
  36.7%
21
  33.9%
5 (Markedly ill)
22
  68.8%
19
  63.3%
41
  66.1%
[1]
Measure Description: A categorical measure of severity ranging from 1 ("Normal, not at all ill") to 7 ("Among the most extremely ill patients.").
1.Primary Outcome
Title ADHD-IV Rating Scale (ADHD-RS)
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for some visits.
Arm/Group Title Active eTNS Sham eTNS
Hide Arm/Group Description:

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. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

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. Following double-blind phase, interested participants randomized to sham have an option for a 4-week open TNS trial. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

Overall Number of Participants Analyzed 32 30
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 32 participants 30 participants
32.12  (1.39) 32.83  (1.43)
Week 1 Number Analyzed 32 participants 30 participants
26.16  (1.39) 28.53  (1.43)
Week 2 Number Analyzed 32 participants 29 participants
24.74  (1.40) 28.31  (1.48)
Week 3 Number Analyzed 32 participants 27 participants
23.92  (1.42) 28.78  (1.50)
Week 4 Number Analyzed 32 participants 29 participants
23.38  (1.40) 27.50  (1.46)
Week 5 Number Analyzed 31 participants 28 participants
25.5  (1.40) 29.1  (1.47)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .54
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = .38, df = 1/228.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments p < .05 for statistical significance
Method Mixed Models Analysis
Comments Time: F=39.97, df = 1/228
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .005
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = 8.12, df = 1/228.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time2: F = 28.96, df = 1/228.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .02
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 6.23, df = 1/57.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .05
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = 4.18, df = 1/57.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .73
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = .12, df = 1/57.
2.Secondary Outcome
Title Clinical Global Impression - Improvement (CGI-I)
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for some visits.
Arm/Group Title Active eTNS Sham eTNS
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 32 30
Measure Type: Count of Participants
Unit of Measure: Participants
Week 1 Number Analyzed 32 participants 30 participants
Improved
8
  25.0%
4
  13.3%
Not Improved
24
  75.0%
26
  86.7%
Week 2 Number Analyzed 31 participants 26 participants
Improved
12
  38.7%
4
  15.4%
Not Improved
19
  61.3%
22
  84.6%
Week 3 Number Analyzed 30 participants 25 participants
Improved
14
  46.7%
3
  12.0%
Not Improved
16
  53.3%
22
  88.0%
Week 4 Number Analyzed 31 participants 28 participants
Improved
16
  51.6%
4
  14.3%
Not Improved
15
  48.4%
24
  85.7%
Week 5 Number Analyzed 31 participants 28 participants
Improved
4
  12.9%
2
   7.1%
Not Improved
27
  87.1%
26
  92.9%
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Assessed effects of group and time on categorical measure CGI-I from Baseline through Visit 4.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .003
Comments p < .05 for statistical significance
Method Chi-squared
Comments Group: F = 8.75, df = 1/168.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Assessed effects of group and time on categorical measure CGI-I from Baseline through Visit 4.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .17
Comments p < .05 for statistical significance.
Method Chi-squared
Comments Time: F = 1.69, df = 3/168.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1b: Assessed effects of group on categorical measure CGI-I from at Visit 5 compared to baseline.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .46
Comments [Not Specified]
Method Chi-squared
Comments Group: Chi-square = .53, df = 1.
3.Secondary Outcome
Title Conners Global Index - Parent Report
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for some visits.
Arm/Group Title Active eTNS Sham eTNS
Hide Arm/Group Description:

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. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

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. Following double-blind phase, interested participants randomized to sham have an option for a 4-week open TNS trial. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

Overall Number of Participants Analyzed 32 30
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 32 participants 30 participants
18.3  (1.1) 17.4  (1.1)
Week 1 Number Analyzed 32 participants 30 participants
15.7  (1.1) 16.5  (1.1)
Week 2 Number Analyzed 32 participants 29 participants
13.0  (1.1) 15.2  (1.2)
Week 3 Number Analyzed 32 participants 27 participants
13.4  (1.1) 15.2  (1.2)
Week 4 Number Analyzed 32 participants 29 participants
14.7  (14.7) 14.6  (1.2)
Week 5 Number Analyzed 31 participants 28 participants
14.1  (1.1) 15.7  (1.2)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .91
Comments [Not Specified]
Method Mixed Models Analysis
Comments Group: F=.01; df =1/209.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .0004
Comments [Not Specified]
Method Mixed Models Analysis
Comments Time: F=13.03; df = 1/209.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .37
Comments [Not Specified]
Method Mixed Models Analysis
Comments Group * time: F = .83; df = 1/209.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .007
Comments Time2: F = 7.45, df = 1/209.
Method Mixed Models Analysis
Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .67
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = .19, df = 1/59.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .68
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = .17, df = 1/50.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .16
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = 2.05, df = 1/50.
4.Secondary Outcome
Title Affective Reactivity Index (ARI) - Child
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for some visits
Arm/Group Title Active eTNS Sham eTNS
Hide Arm/Group Description:

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. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

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. Following double-blind phase, interested participants randomized to sham have an option for a 4-week open TNS trial. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

Overall Number of Participants Analyzed 32 30
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 32 participants 30 participants
4.5  (.5) 4.5  (.5)
Week 4 Number Analyzed 32 participants 29 participants
4.1  (.5) 3.8  (.6)
Week 5 Number Analyzed 31 participants 28 participants
3.9  (.5) 3.5  (.6)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .91
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = .01, df = 1/56.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .15
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 2.12, df = .15
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .64
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = .21, df = 1/56.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .66
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = .20, df = 1/59.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .48
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = .50, df = 1/47.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .81
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = .06, df = 1/47.
5.Secondary Outcome
Title Affective Reactivity Index (ARI) - Parent Report
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for some visits.
Arm/Group Title Active eTNS Sham eTNS
Hide Arm/Group Description:

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. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

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. Following double-blind phase, interested participants randomized to sham have an option for a 4-week open TNS trial. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

Overall Number of Participants Analyzed 32 30
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 32 participants 30 participants
4.4  (.6) 4.5  (.6)
Week 4 Number Analyzed 32 participants 29 participants
3.6  (.6) 3.6  (.7)
Week 5 Number Analyzed 31 participants 28 participants
3.8  (.7) 4.2  (.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .89
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = .02, df = 1/55.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .14
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 2.28, df = 1/55.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .80
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = .06, df = .81.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .93
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = .01, df = 1/58.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .15
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 2.22, df = 1/35.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .28
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = 1.23, df = 1/35.
6.Secondary Outcome
Title Multidimensional Anxiety Scale for Children (MASC) - Child Report
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing from some visits.
Arm/Group Title Active eTNS Sham eTNS
Hide Arm/Group Description:

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. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

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. Following double-blind phase, interested participants randomized to sham have an option for a 4-week open TNS trial. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

Overall Number of Participants Analyzed 32 30
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 32 participants 30 participants
61.0  (4.7) 61.0  (4.9)
Week 4 Number Analyzed 32 participants 29 participants
59.5  (4.8) 56.4  (4.7)
Week 5 Number Analyzed 31 participants 28 participants
56.1  (5.0) 52.3  (5.3)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .91
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = .01; df = 1/46.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .11
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 2.62, df = 1/46.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .40
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = .71; df = .40.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .49
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = .48. df = 1/55.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .18
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 1.87, df = 1/55.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .72
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = .13, df = 1/38.
7.Secondary Outcome
Title Multidimensional Anxiety Scale for Children (MASC) - Parent Report
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for some visits.
Arm/Group Title Active eTNS Sham eTNS
Hide Arm/Group Description:

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. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

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. Following double-blind phase, interested participants randomized to sham have an option for a 4-week open TNS trial. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

Overall Number of Participants Analyzed 32 30
Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 32 participants 30 participants
46.2  (3.0) 48.4  (3.1)
Week 4 Number Analyzed 32 participants 29 participants
33.9  (3.0) 42.9  (3.2)
Week 5 Number Analyzed 31 participants 28 participants
32.4  (2.9) 38.2  (3.0)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .62
Comments [Not Specified]
Method Mixed Models Analysis
Comments Group: F =.25, df = 1/53.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .06
Comments [Not Specified]
Method Mixed Models Analysis
Comments Time: F = 3.58, df = 1/53.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .09
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = 2.90, df 1/53.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .06
Comments p < .05 for statistical significance
Method Mixed Models Analysis
Comments Group: F = 3.36, df = 1/58.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .05
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 4.20, df = 1/31.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .42
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = .66, df = 1/31.
8.Secondary Outcome
Title Height
Hide Description A dimensional measure assessed in centimeters (cm).
Time Frame Change over baseline and weeks 1, 4, and 5.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for some visits.
Arm/Group Title Active TNS Sham TNS
Hide Arm/Group Description:

Active TNS

Active TNS: Participants randomized to active trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep.

Sham TNS

Sham TNS: Participants randomized to sham trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep.

Overall Number of Participants Analyzed 32 30
Least Squares Mean (Standard Error)
Unit of Measure: cm.
Baseline Number Analyzed 32 participants 30 participants
142.82  (1.78) 141.45  (1.84)
Week 1 Number Analyzed 32 participants 30 participants
142.79  (1.78) 141.57  (1.84)
Week 4 Number Analyzed 32 participants 29 participants
143.14  (1.78) 142.31  (1.84)
Week 5 Number Analyzed 31 participants 28 participants
143.58  (1.81) 142.30  (1.90)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .29
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = 0.29, df = 1/129.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .02
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 5.83, df = 1/129.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .31
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = 1.03, df = 1/129.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .69
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = .16, df = 1/59.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .33
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = .98, df = 1/54.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .35
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = .88, df = 1/54.
9.Secondary Outcome
Title Weight
Hide Description A dimensional measure assessed in kilograms (kg).
Time Frame Change over baseline and weeks 1, 4, and 5.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for some visits.
Arm/Group Title Active eTNS Sham eTNS
Hide Arm/Group Description:

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. Positive responders will be invited to participate in a 12-month open extension.

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.

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. Following double-blind phase, interested participants randomized to sham have an option for a 4-week open TNS trial. Positive responders will be invited to participate in a 12-month open extension.

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.

Overall Number of Participants Analyzed 32 30
Least Squares Mean (Standard Error)
Unit of Measure: kg.
Baseline Number Analyzed 32 participants 30 participants
38.83  (1.88) 35.34  (1.95)
Week 1 Number Analyzed 32 participants 30 participants
39.12  (1.88) 35.58  (1.95)
Week 4 Number Analyzed 32 participants 29 participants
39.65  (1.88) 35.67  (1.95)
Week 5 Number Analyzed 31 participants 28 participants
39.85  (1.93) 35.71  (2.03)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .21
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = 1.62, df = 1/128.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .02
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 5.18, df = 1/128.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .01
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = 6.89, df = 1/128.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .15
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F= 2.16, df = 1/59.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .05
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 4.15, df = 1/55.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .79
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = .07, df = 1/55.
10.Secondary Outcome
Title Systolic Blood Pressure
Hide Description A dimensional measure expressed in mm mercury (Hg).
Time Frame Change over baseline and weeks 1, 4, and 5.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing from some visits.
Arm/Group Title Active TNS Sham TNS
Hide Arm/Group Description:

Active TNS

Active TNS: Participants randomized to active trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep.

Sham TNS

Sham TNS: Participants randomized to sham trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep.

Overall Number of Participants Analyzed 32 30
Least Squares Mean (Standard Error)
Unit of Measure: mm Hg.
Baseline Number Analyzed 32 participants 30 participants
108.50  (2.26) 106.10  (2.36)
Week 1 Number Analyzed 32 participants 30 participants
107.03  (2.26) 109.20  (2.34)
Week 4 Number Analyzed 32 participants 29 participants
111.00  (2.26) 107.79  (2.36)
Week 5 Number Analyzed 31 participants 28 participants
112.26  (2.02) 106.10  (2.13)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .94
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = .01, df = 1/128.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .76
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = .09, df = 1/128.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .39
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = .75, df =1/128.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .09
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = 3.06, df = 1/59.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .79
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = .07, df = 1/55.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .22
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = 1.55, df = 1/55.
11.Secondary Outcome
Title Diastolic Blood Pressure
Hide Description A dimensional measure assessed in mm mercury (Hg).
Time Frame Change over baseline and weeks 1, 4, and 5.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for some visits.
Arm/Group Title Active TNS Sham TNS
Hide Arm/Group Description:

Active TNS

Active TNS: Participants randomized to active trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep.

Sham TNS

Sham TNS: Participants randomized to sham trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep.

Overall Number of Participants Analyzed 32 30
Least Squares Mean (Standard Error)
Unit of Measure: mm Hg.
Baseline Number Analyzed 32 participants 30 participants
64.97  (1.66) 63.61  (1.73)
Week 1 Number Analyzed 32 participants 30 participants
63.69  (1.66) 62.33  (1.71)
Week 4 Number Analyzed 32 participants 29 participants
65.09  (1.66) 61.01  (1.73)
Week 5 Number Analyzed 31 participants 28 participants
65.30  (1.76) 60.89  (1.86)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .64
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = .22, df = 1/128.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .19
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 1.49, df = 1/128.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .22
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = 1.49, df = 1/128.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .05
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = 3.95, df = 1/59.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .96
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 0.00, df = 1/55.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .92
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = .01, df = 1/55.
12.Secondary Outcome
Title Pulse
Hide Description Heart rate in beats per minute (bpm).
Time Frame Change over baseline and weeks weeks 1, 4, and 5.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for some visits.
Arm/Group Title Active TNS Sham TNS
Hide Arm/Group Description:

Active TNS

Active TNS: Participants randomized to active trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep.

Sham TNS

Sham TNS: Participants randomized to sham trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep.

Overall Number of Participants Analyzed 32 30
Least Squares Mean (Standard Error)
Unit of Measure: bpm.
Baseline Number Analyzed 32 participants 30 participants
76.69  (2.27) 76.70  (2.37)
Week 1 Number Analyzed 32 participants 30 participants
79.91  (2.27) 79.70  (2.34)
Week 4 Number Analyzed 32 participants 29 participants
81.78  (2.27) 75.18  (2.37)
Week 5 Number Analyzed 31 participants 28 participants
79.42  (2.10) 78.18  (2.22)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .79
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = .07, df = 1/128.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .30
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = 1.10, df = 1/128.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .03
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = 4.61, df = 1/128.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .14
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group: F = 2.24, df = 1/59.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .82
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Time: F = .05, df = 1/55.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active TNS, Sham TNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .07
Comments p < .05 for statistical significance.
Method Mixed Models Analysis
Comments Group * time: F = 3.35, df = 1/55.
13.Secondary Outcome
Title Children's Depression Inventory (CDI)
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Data missing for some visits.
Arm/Group Title Active eTNS Sham eTNS
Hide Arm/Group Description:

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. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

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. Following double-blind phase, interested participants randomized to sham have an option for a 4-week open TNS trial. Positive responders will be invited to participate in a 12-month open extension.

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 active eTNS in a 12 month extension period.

Overall Number of Participants Analyzed 32 30
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 32 participants 30 participants
10.14  (1.23) 9.10  (1.23)
Week 4 Number Analyzed 32 participants 29 participants
8.94  (1.22) 8.21  (1.24)
Week 5 Number Analyzed 31 participants 28 participants
7.88  (1.32) 7.34  (1.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .55
Comments [Not Specified]
Method Mixed Models Analysis
Comments Group: F = .36, df = 1/52
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1a: Outcomes were fitted via a mixed model with group, time, and group-by-time interactions to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .34
Comments [Not Specified]
Method Mixed Models Analysis
Comments Time: F = .09, df = 1/52
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments Phase 1 a: Outcomes were fitted via a mixed effects model with group, time, and group-by-time interaction to test for treatment effects.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .81
Comments [Not Specified]
Method Mixed Models Analysis
Comments Group * time: F = .06, df = 1/52
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .83
Comments [Not Specified]
Method Mixed Models Analysis
Comments Group: F = .05, df = 1/59
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .04
Comments [Not Specified]
Method Mixed Models Analysis
Comments Time: F = 4.52, df = 1/43
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .73
Comments [Not Specified]
Method Mixed Models Analysis
Comments Group * time: F = .12, df = 1/43
14.Secondary Outcome
Title Conners Global Index - Teacher
Hide Description 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.
Hide Outcome Measure Data
Hide Analysis Population Description
Results may not be valid due to problems with data collection leading to substantial missing data.
Arm/Group Title Active eTNS Sham eTNS
Hide Arm/Group Description:

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.

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.

Overall Number of Participants Analyzed 32 30
Least Squares Mean (Standard Error)
Unit of Measure: score on a scale
Baseline Number Analyzed 13 participants 11 participants
15.76  (1.32) 15.15  (1.32)
Week 1 Number Analyzed 17 participants 11 participants
15.86  (1.23) 11.37  (1.46)
Week 2 Number Analyzed 15 participants 6 participants
14.36  (1.27) 15.64  (1.77)
Week 3 Number Analyzed 9 participants 5 participants
14.56  (1.92) 16.56  (1.92)
Week 4 Number Analyzed 6 participants 5 participants
15.43  (1.69) 14.53  (1.89)
Week 5 Number Analyzed 3 participants 2 participants
11.54  (3.33) 18.83  (3.89)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .21
Comments [Not Specified]
Method Mixed Models Analysis
Comments Group: F = 1.62, df = 1/58.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .39
Comments [Not Specified]
Method Mixed Models Analysis
Comments Time: F = .74, df = 1/58.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .18
Comments [Not Specified]
Method Mixed Models Analysis
Comments Time2: F = 1.88, df = 1/58.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .22
Comments [Not Specified]
Method Mixed Models Analysis
Comments Group * time: F = 1.56; df = 1/58.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value .21
Comments [Not Specified]
Method Mixed Models Analysis
Comments Group: F = 1.72, df = 1/12.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1
Comments Test not valid due to insufficient data.
Method Mixed Models Analysis
Comments Time: F = 0.00, df = 1/0.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Active eTNS, Sham eTNS
Comments 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.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 1
Comments Test not valid due to insufficient data.
Method Mixed Models Analysis
Comments Group * time: F = .87, df = 1/0.
15.Other Pre-specified Outcome
Title Affective Posner Task
Hide Description A laboratory measure of frustration tolerance.
Time Frame Baseline, and Weeks 1 and 4
Outcome Measure Data Not Reported
16.Other Pre-specified Outcome
Title Attention Network Task (ANT) Response Inhibition
Hide Description A computer-administered laboratory measure of executive function.
Time Frame Baseline, Weeks 1 and 4
Outcome Measure Data Not Reported
17.Other Pre-specified Outcome
Title Spatial Working Memory (SWM)
Hide Description A computer-administered laboratory measure of executive function.
Time Frame Baseline, Weeks 1 and 4
Outcome Measure Data Not Reported
18.Other Pre-specified Outcome
Title Electroencephalography (EEG)
Hide Description A laboratory measure of cortical activity.
Time Frame Baseline and Week 4
Outcome Measure Data Not Reported
19.Other Pre-specified Outcome
Title Behavior Rating Inventory of Executive Functioning (BRIEF)
Hide Description 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.
Outcome Measure Data Not Reported
20.Other Pre-specified Outcome
Title Children's Sleep Habits Questionnaire (CSHQ)
Hide Description 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.
Outcome Measure Data Not Reported
Time Frame Data were collected over the double-blind study, beginning at baseline and then weekly for 5 weeks.
Adverse Event Reporting Description Adverse events were solicited via a structured side effects questionnaire and open inquiry completed at baseline and each weekly visit during the double-blind phases.
 
Arm/Group Title Active TNS Sham TNS
Hide Arm/Group Description

Active TNS

Active TNS: Participants randomized to active trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep.

Sham TNS

Sham TNS: Participants randomized to sham trigeminal nerve stimulation (TNS) administered by the Monarch eTNS System nightly during sleep.

All-Cause Mortality
Active TNS Sham TNS
Affected / at Risk (%) Affected / at Risk (%)
Total   0/32 (0.00%)      0/30 (0.00%)    
Hide Serious Adverse Events
Active TNS Sham TNS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/32 (0.00%)      0/30 (0.00%)    
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Active TNS Sham TNS
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/32 (71.88%)      22/30 (73.33%)    
Cardiac disorders     
Rapid heartbeat   1/32 (3.13%)  1 0/30 (0.00%)  0
Gastrointestinal disorders     
Nausea   1/32 (3.13%)  1 0/30 (0.00%)  0
Stomachache   2/32 (6.25%)  2 1/30 (3.33%)  2
Constipation   3/32 (9.38%)  6 3/30 (10.00%)  10
General disorders     
Decreased appetite   1/32 (3.13%)  1 1/30 (3.33%)  1
Increased appetite   6/32 (18.75%)  13 2/30 (6.67%)  2
Fatigue   4/32 (12.50%)  4 1/30 (3.33%)  1
Musculoskeletal and connective tissue disorders     
Muscle cramps   1/32 (3.13%)  1 1/30 (3.33%)  1
Muscle twitching   0/32 (0.00%)  0 2/30 (6.67%)  3
Nervous system disorders     
Drowsy   7/32 (21.88%)  9 4/30 (13.33%)  5
Tingling   1/32 (3.13%)  1 0/30 (0.00%)  0
Headache   4/32 (12.50%)  4 0/30 (0.00%)  0
Tremor   0/32 (0.00%)  0 1/30 (3.33%)  2
Slurred speech   0/32 (0.00%)  0 1/30 (3.33%)  1
Frequent sweating   1/32 (3.13%)  1 1/30 (3.33%)  1
Difficulty finding words   0/32 (0.00%)  0 3/30 (10.00%)  6
Psychiatric disorders     
Trouble sleeping   6/32 (18.75%)  11 5/30 (16.67%)  6
Nightmares   2/32 (6.25%)  2 0/30 (0.00%)  0
Hyperactive   13/32 (40.63%)  27 19/30 (63.33%)  40
Feels strange   0/32 (0.00%)  0 2/30 (6.67%)  2
Apathy   2/32 (6.25%)  2 3/30 (10.00%)  3
Clenching teeth   4/32 (12.50%)  6 3/30 (10.00%)  3
Wish to be dead.  [1]  0/32 (0.00%)  0 0/30 (0.00%)  0
Non-specific active suicidal thoughts  [1]  0/32 (0.00%)  0 0/30 (0.00%)  0
Active suicidal ideation without intent   0/32 (0.00%)  0 0/30 (0.00%)  0
Active suicidal ideation with some intent  [1]  0/32 (0.00%)  0 0/30 (0.00%)  0
Active suicidal ideation with active plan and intent  [1]  0/32 (0.00%)  0 0/30 (0.00%)  0
Renal and urinary disorders     
Frequent urination   2/32 (6.25%)  5 0/30 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
Stuffy nose   5/32 (15.63%)  5 6/30 (20.00%)  7
Trouble catching breath   1/32 (3.13%)  1 1/30 (3.33%)  1
Skin and subcutaneous tissue disorders     
Skin rash   2/32 (6.25%)  2 0/30 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Based on Columbia-Suicide Severity Rating Scale (C-SSRS)
Insufficient data were collected with the Conners Teacher Report leading to small number of participants analyzed. Results are likely not valid.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: James McGough, M.D.
Organization: University of California, Los Angeles
Phone: 310-794-7841
EMail: jmcgough@mednet.ucla.edu
Layout table for additonal information
Responsible Party: James McGough, University of California, Los Angeles
ClinicalTrials.gov Identifier: NCT02155608    
Other Study ID Numbers: NIMH R34MH101282
R34MH101282 ( U.S. NIH Grant/Contract )
First Submitted: June 2, 2014
First Posted: June 4, 2014
Results First Submitted: February 26, 2019
Results First Posted: April 12, 2019
Last Update Posted: July 2, 2019