HIRREM Developmental Study

• ClinicalTrials.gov Identifier: NCT02709369
• Recruitment Status: Completed
• First Posted: March 16, 2016
• Results First Posted: December 24, 2019
• Last Update Posted: December 24, 2019
• Sponsor: Wake Forest University Health Sciences
• Information provided by (Responsible Party): Wake Forest University Health Sciences

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Sleep Initiation and Maintenance Disorders; Anxiety; Post-Traumatic Stress Disorder; Hot Flashes; Headache; Traumatic Brain Injury; Post Concussion Symptoms
• Intervention: Device: HIRREM
• Enrollment: 300

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Active HIRREM
Arm/Group Description	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Period Title: Overall Study
Started	300
Completed	273
Not Completed	27
Reason Not Completed
Lost to Follow-up	15
Withdrawal by Subject	10
Did not received intervention	2

Baseline Characteristics

Arm/Group Title		Active HIRREM
Arm/Group Description		This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Baseline Participants		300
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	300 participants
	<=18 years	30 10.0%
	Between 18 and 65 years	228 76.0%
	>=65 years	42 14.0%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	300 participants
	Female	166 55.3%
	Male	134 44.7%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants	Number Analyzed	300 participants
African American		15 5.0%
Asian		5 1.7%
Hispanic or Latino		3 1.0%
White		276 92.0%
Other		1 0.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	300 participants
		300

Outcome Measures

1. Primary Outcome

Title	Heart Rate Variability Standard Deviation of NN Intervals (SDNN)
Description	Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval
Time Frame	Baseline/Enrollment visit

Outcome Measure Data

Analysis Population Description

BIOPAC device was acquired prior to subject 38. Other entries were excluded due to missing or dropped heartbeats.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	227
Mean (Standard Deviation); Unit of Measure: milliseconds
	44.41 (22.94)

2. Primary Outcome

Title	Heart Rate Variability (SDNN)
Description	Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval
Time Frame	Up to 2 weeks after the intervention is completed

Outcome Measure Data

Analysis Population Description

BIOPAC device was acquired prior to subject 38. Other entries were excluded due to missing or dropped heartbeats.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	227
Mean (Standard Deviation); Unit of Measure: milliseconds
	54.82 (30.63)

3. Primary Outcome

Title	Baroreflex Sensitivity High Frequency (HF) Alpha
Description	Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Time Frame	Baseline/Enrollment visit

Outcome Measure Data

Analysis Population Description

BIOPAC device was acquired prior to subject 38. Other entries were excluded due to missing or dropped heartbeats.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	227
Mean (Standard Deviation); Unit of Measure: ms^2
	18.81 (14.45)

4. Primary Outcome

Title	Baroreflex Sensitivity High Frequency (HF) Alpha
Description	Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Time Frame	Up to two weeks after the intervention is completed

Outcome Measure Data

Analysis Population Description

BIOPAC device was acquired prior to subject 38. Other entries were excluded due to missing or dropped heartbeats.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	227
Mean (Standard Deviation); Unit of Measure: ms^2
	26.68 (20.69)

5. Primary Outcome

Title	Baroreflex Sensitivity Sequence Up
Description	Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Time Frame	Baseline/Enrollment visit

Outcome Measure Data

Analysis Population Description

BIOPAC device was acquired prior to subject 38. Other entries were excluded due to missing or dropped heartbeats.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	226
Mean (Standard Deviation); Unit of Measure: ms/mmHg
	15.39 (13.88)

6. Primary Outcome

Title	Baroreflex Sensitivity Sequence Up
Description	Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Time Frame	Up to two weeks after the intervention is completed

Outcome Measure Data

Analysis Population Description

BIOPAC device was acquired prior to subject 38. Other entries were excluded due to missing or dropped heartbeats.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	226
Mean (Standard Deviation); Unit of Measure: ms/mmHg
	14.15 (11.56)

7. Primary Outcome

Title	Baroreflex Sensitivity Sequence Down
Description	Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Time Frame	Baseline/Enrollment visit

Outcome Measure Data

Analysis Population Description

BIOPAC device was acquired prior to subject 38. Other entries were excluded due to missing or dropped heartbeats.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	227
Mean (Standard Deviation); Unit of Measure: ms/mmHg
	14.15 (11.56)

8. Primary Outcome

Title	Baroreflex Sensitivity Sequence Down
Description	Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Time Frame	Up to two weeks after the intervention is completed

Outcome Measure Data

Analysis Population Description

BIOPAC device was acquired prior to subject 38. Other entries were excluded due to missing or dropped heartbeats.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	227
Mean (Standard Deviation); Unit of Measure: ms/mmHg
	20.73 (16.76)

9. Primary Outcome

Title	Baroreflex Sensitivity Sequence All
Description	Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Time Frame	Baseline/Enrollment visit

Outcome Measure Data

Analysis Population Description

BIOPAC device was acquired prior to subject 38. Other entries were excluded due to missing or dropped heartbeats.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	227
Mean (Standard Deviation); Unit of Measure: ms/mmHg
	14.63 (11.80)

10. Primary Outcome

Title	Baroreflex Sensitivity Sequence All
Description	Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Time Frame	Up to 2 weeks after the intervention is completed

Outcome Measure Data

Analysis Population Description

BIOPAC device was acquired prior to subject 38. Other entries were excluded due to missing or dropped heartbeats.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	227
Mean (Standard Deviation); Unit of Measure: ms/mmHg
	20.74 (16.30)

11. Secondary Outcome

Title	Center for Epidemiologic Studies Depression Scale (CES-D)
Description	The CES-D is a 20-item survey assessing affective depressive symptomatology to screen for risk of depression. Scores range from 0-60, with a score of 16 commonly used as a clinically relevant cut-off. Higher scores suggest the presence of more symptomatology.
Time Frame	enrollment visit/baseline

Outcome Measure Data

Analysis Population Description

CES-D was temporarily removed as approved measure of depression (35 subjects). Other entries were excluded if there was incomplete or missing data.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	233
Mean (Standard Deviation); Unit of Measure: score on a scale
	18.12 (12.16)

12. Secondary Outcome

Title	Center for Epidemiologic Studies Depression Scale (CES-D)
Description	The CES-D is a 20-item survey assessing affective depressive symptomatology to screen for risk of depression. Scores range from 0-60, with a score of 16 commonly used as a clinically relevant cut-off. Higher scores suggest the presence of more symptomatology.
Time Frame	1-2 weeks after intervention is completed

Outcome Measure Data

Analysis Population Description

CES-D was temporarily removed as approved measure of depression (35 subjects). Other entries were excluded if there was incomplete or missing data.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	233
Mean (Standard Deviation); Unit of Measure: score on a scale
	10.00 (8.96)

13. Secondary Outcome

Title	Center for Epidemiologic Studies Depression Scale (CES-D)
Description	The CES-D is a 20-item survey assessing affective depressive symptomatology to screen for risk of depression. Scores range from 0-60, with a score of 16 commonly used as a clinically relevant cut-off. Higher scores suggest the presence of more symptomatology.
Time Frame	4-8 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

CES-D was temporarily removed as approved measure of depression (35 subjects). Other entries were excluded if there was incomplete or missing data. Late data collection visit was added at after participant 65. Out of town subjects typically were not able to make it back for late data collections.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	115
Mean (Standard Deviation); Unit of Measure: score on a scale
	8.91 (8.28)

14. Secondary Outcome

Title	Euro Quality of Life--Five Dimension (EQ-5D)
Description	The EQ-5D is a brief, standardized measure of health status developed by the EuroQol Group, and is a paper and pencil survey providing a single index value for health status. The score reported is current health status which ranges from 0 to 100 with a higher score denoting a better outcome.
Time Frame	enrollment visit/baseline

Outcome Measure Data

Analysis Population Description

EQ-5D was added as a study measure at subject 79. Entries were excluded if there was incomplete or missing data.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	202
Mean (Standard Deviation); Unit of Measure: score on a scale
	69.55 (19.69)

15. Secondary Outcome

Title	Euro Quality of Life--Five Dimension (EQ-5D)
Description	The EQ-5D is a brief, standardized measure of health status developed by the EuroQol Group, and is a paper and pencil survey providing a single index value for health status. The score reported is current health status which ranges from 0 to 100 with a higher score denoting a better outcome.
Time Frame	1-2 weeks after the intervention is completed

Outcome Measure Data

Analysis Population Description

EQ-5D was added as a study measure at subject 79. Entries were excluded if there was incomplete or missing data.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	202
Mean (Standard Deviation); Unit of Measure: score on a scale
	79.12 (16.42)

16. Secondary Outcome

Title	Euro Quality of Life--Five Dimension (EQ-5D)
Description	The EQ-5D is a brief, standardized measure of health status developed by the EuroQol Group, and is a paper and pencil survey providing a single index value for health status. The score reported is current health status which ranges from 0 to 100 with a higher score denoting a better outcome.
Time Frame	4-8 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

EQ-5D was added as a study measure at subject 79. Entries were excluded if there was incomplete or missing data. Late data collection visit was added at after participant 65. Out of town subjects typically were not able to make it back for late data collections.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	151
Mean (Standard Deviation); Unit of Measure: score on a scale
	78.36 (17.84)

17. Secondary Outcome

Title	Generalized Anxiety Disorder-7 (GAD-7)
Description	The Generalized Anxiety Disorder-7 (GAD-7) is a seven item screening tool for anxiety that is widely used in primary care. Scores range from 0 to 21 with higher scores suggesting anxiety.
Time Frame	enrollment visit/baseline

Outcome Measure Data

Analysis Population Description

GAD-7 was temporarily removed as approved measure of depression (35 subjects). Other entries were excluded if there was incomplete or missing data.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	167
Mean (Standard Deviation); Unit of Measure: score on a scale
	8.31 (6.01)

18. Secondary Outcome

Title	Generalized Anxiety Disorder-7 (GAD-7)
Description	The Generalized Anxiety Disorder-7 (GAD-7) is a seven item screening tool for anxiety that is widely used in primary care. Scores range from 0 to 21 with higher scores suggesting anxiety.
Time Frame	1-2 weeks after the intervention is completed

Outcome Measure Data

Analysis Population Description

GAD-7 was temporarily removed as approved measure of depression (35 subjects). Other entries were excluded if there was incomplete or missing data.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	167
Mean (Standard Deviation); Unit of Measure: score on a scale
	4.35 (4.19)

19. Secondary Outcome

Title	Generalized Anxiety Disorder-7 (GAD-7)
Description	The Generalized Anxiety Disorder-7 (GAD-7) is a seven item screening tool for anxiety that is widely used in primary care. Scores range from 0 to 21 with higher scores suggesting anxiety.
Time Frame	4-8 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

GAD-7 was temporarily removed as approved measure of depression (35 subjects). Other entries were excluded if there was incomplete or missing data. Late data collection visit was added at after participant 65. Out of town subjects typically were not able to make it back for late data collections.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	133
Mean (Standard Deviation); Unit of Measure: score on a scale
	3.66 (3.49)

20. Secondary Outcome

Title	Insomnia Severity Index (ISI)
Description	The ISI measures the severity of insomnia symptoms. The ISI is a 7 question measure, with responses from 0-4 for each question, yielding scores ranging from 0-28 where lower scores denote a healthier sleep quality.
Time Frame	enrollment visit/baseline

Outcome Measure Data

Analysis Population Description

Entries were excluded if there was incomplete or missing data.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	272
Mean (Standard Deviation); Unit of Measure: score on a scale
	13.47 (7.17)

21. Secondary Outcome

Title	Insomnia Severity Index (ISI)
Description	The ISI measures the severity of insomnia symptoms. The ISI is a 7 question measure, with responses from 0-4 for each question, yielding scores ranging from 0-28 where lower scores denote a healthier sleep quality.
Time Frame	1-2 weeks after the intervention is completed

Outcome Measure Data

Analysis Population Description

Entries were excluded if there was incomplete or missing data.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	270
Mean (Standard Deviation); Unit of Measure: score on a scale
	7.09 (5.90)

22. Secondary Outcome

Title	Insomnia Severity Index (ISI)
Description	The ISI measures the severity of insomnia symptoms. The ISI is a 7 question measure, with responses from 0-4 for each question, yielding scores ranging from 0-28 where lower scores denote a healthier sleep quality.
Time Frame	4-8 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

Entries were excluded if there was incomplete or missing data. Late data collection visit was added at after participant 65. Out of town subjects typically were not able to make it back for late data collections.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	160
Mean (Standard Deviation); Unit of Measure: score on a scale
	6.22 (5.43)

23. Secondary Outcome

Title	Posttraumatic Stress Disorder Checklist (PCL-C)
Description	The PCL - Civilian (C) is a symptom checklist to measure stress severity due to a traumatic experience, in civilian settings. Seventeen items are rated on a Likert scale with a composite score range of 17 to 85. A score of 44 or higher correlates with probability of civilian-related PTSD.
Time Frame	enrollment visit/baseline

Outcome Measure Data

Analysis Population Description

Entries were excluded if there was incomplete or missing data. Scale was exploratory and only administered to people who self-reported trauma or PTSD on medical history form.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	179
Mean (Standard Deviation); Unit of Measure: score on a scale
	38.75 (15.43)

24. Secondary Outcome

Title	Posttraumatic Stress Disorder Checklist (PCL)
Description	The PCL - Civilian (C) is a symptom checklist to measure stress severity due to a traumatic experience, in civilian settings. Seventeen items are rated on a Likert scale with a composite score range of 17 to 85. A score of 44 or higher correlates with probability of civilian-related PTSD.
Time Frame	1-2 weeks after the intervention is completed

Outcome Measure Data

Analysis Population Description

Entries were excluded if there was incomplete or missing data. Scale was exploratory and only administered to people who self-reported trauma or PTSD on medical history form.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	179
Mean (Standard Deviation); Unit of Measure: score on a scale
	28.50 (11.37)

25. Secondary Outcome

Title	Posttraumatic Stress Disorder Checklist (PCL)
Description	The PCL - Civilian (C) is a symptom checklist to measure stress severity due to a traumatic experience, in civilian settings. Seventeen items are rated on a Likert scale with a composite score range of 17 to 85. A score of 44 or higher correlates with probability of civilian-related PTSD.
Time Frame	4-8 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

Entries were excluded if there was incomplete or missing data. Scale was exploratory and only administered to people who self-reported trauma or PTSD on medical history form. Late data collection visit was added at after participant 65. Out of town subjects typically were not able to make it back for late data collections.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	91
Mean (Standard Deviation); Unit of Measure: score on a scale
	26.13 (9.58)

26. Secondary Outcome

Title	Rivermead Post-Concussion Symptoms Questionnaire (RPQ)
Description	The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) is a 16-item survey that assesses the severity of the most common post-concussion symptoms on a scale of 0 to 4, with a total score range from 0 to 64 with 64 denoting the greatest symptom severity.
Time Frame	enrollment visit/baseline

Outcome Measure Data

Analysis Population Description

Entries were excluded if there was incomplete or missing data. Scale was exploratory and only administered to people who self-reported TBI or concussion on medical history form.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	48
Mean (Standard Deviation); Unit of Measure: score on a scale
	29.60 (12.82)

27. Secondary Outcome

Title	Rivermead Post-Concussion Symptoms Questionnaire (RPQ)
Description	The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) is a 16-item survey that assesses the severity of the most common post-concussion symptoms on a scale of 0 to 4, with a total score range from 0 to 64 with a higher score denoting the greatest symptom severity.
Time Frame	1-2 weeks after the intervention is completed

Outcome Measure Data

Analysis Population Description

Entries were excluded if there was incomplete or missing data. Scale was exploratory and only administered to people who self-reported TBI or concussion on medical history form.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	48
Mean (Standard Deviation); Unit of Measure: score on a scale
	15.79 (13.96)

28. Secondary Outcome

Title	Rivermead Post-Concussion Symptoms Questionnaire (RPQ)
Description	The Rivermead Post-Concussion Symptoms Questionnaire (RPQ) is a 16-item survey that assesses the severity of the most common post-concussion symptoms on a scale of 0 to 4, with a total score range from 0 to 64 with 64 denoting the greatest symptom severity.
Time Frame	4-8 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

Entries were excluded if there was incomplete or missing data. Scale was exploratory and only administered to people who self-reported TBI or concussion on medical history form. Late data collection visit was added at after participant 65. Out of town subjects typically were not able to make it back for late data collections.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	35
Mean (Standard Deviation); Unit of Measure: score on a scale
	16.89 (14.74)

29. Secondary Outcome

Title	Drop Stick Reaction Testing
Description	Reaction testing is measured by a drop-stick apparatus that has been validated as a way to quantify the impact of athletic concussion on psychomotor performance. Following two practice trials, participants perform eight trials, and a mean distance value is calculated. Better reaction time is denoted by a lower score. The scores range from 0 to 100.
Time Frame	enrollment visit/baseline

Outcome Measure Data

Analysis Population Description

Drop stick reaction testing was temporarily removed as approved measure of depression (35 subjects). Other entries were excluded if there was incomplete or missing data.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	213
Mean (Standard Deviation); Unit of Measure: cm
	27.20 (8.25)

30. Secondary Outcome

Title	Drop Stick Reaction Testing
Description	Reaction testing is measured by a drop-stick apparatus that has been validated as a way to quantify the impact of athletic concussion on psychomotor performance. Following two practice trials, participants perform eight trials, and a mean distance value is calculated. Better reaction time is denoted by a lower score. The scores range from 0 to 100.
Time Frame	1-2 weeks after the intervention is completed

Outcome Measure Data

Analysis Population Description

Drop stick reaction testing was temporarily removed as approved measure of depression (35 subjects). Other entries were excluded if there was incomplete or missing data.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	213
Mean (Standard Deviation); Unit of Measure: cm
	23.40 (6.78)

31. Secondary Outcome

Title	Drop Stick Reaction Testing
Description	Reaction testing is measured by a drop-stick apparatus that has been validated as a way to quantify the impact of athletic concussion on psychomotor performance. Following two practice trials, participants perform eight trials, and a mean distance value is calculated. Better reaction time is denoted by a lower score. The scores range from 0 to 100.
Time Frame	4-8 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

Drop stick reaction testing was temporarily removed as approved measure of depression (35 subjects). Other entries were excluded if there was incomplete or missing data. Late data collection visit was added at after participant 65. Out of town subjects typically were not able to make it back for late data collections.

Arm/Group Title	Active HIRREM
Arm/Group Description:	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
Overall Number of Participants Analyzed	90
Mean (Standard Deviation); Unit of Measure: cm
	22.58 (5.78)

32. Other Pre-specified Outcome

Title	Heart Rate Variability Standard Deviation of NN Intervals (SDNN)
Description	Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval
Time Frame	4-8 weeks after completion of the intervention

Outcome Measure Data Not Reported

33. Other Pre-specified Outcome

Title	Baroreflex Sensitivity High Frequency (HF) Alpha
Description	Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Time Frame	4-8 weeks after completion of the intervention

Outcome Measure Data Not Reported

34. Other Pre-specified Outcome

Title	Baroreflex Sensitivity Sequence Up
Description	Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Time Frame	4-8 weeks after completion of the intervention

Outcome Measure Data Not Reported

35. Other Pre-specified Outcome

Title	Baroreflex Sensitivity Sequence Down
Description	Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Time Frame	4-8 weeks after completion of the intervention

Outcome Measure Data Not Reported

36. Other Pre-specified Outcome

Title	Baroreflex Sensitivity Sequence All
Description	Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Time Frame	4-8 weeks after completion of the intervention

Outcome Measure Data Not Reported

Adverse Events

Time Frame	Informed consent until 4-8 weeks after completion of the intervention
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Active HIRREM
Arm/Group Description	This is a single site, single-arm, open-label, developmental study. Participants are recruited to receive eight to twenty sessions of High-resolution, relational, resonance-based electroencephalic mirroring (HIRREM), in addition to their usual care.
All-Cause Mortality
	Active HIRREM
	Affected / at Risk (%)
Total	0/300 (0.00%)
Serious Adverse Events
	Active HIRREM
	Affected / at Risk (%)
Total	0/300 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Active HIRREM
	Affected / at Risk (%)
Total	0/300 (0.00%)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

• Name/Title: Dr. Charles H. Tegeler
• Organization: Wake Forest School of Medicine
• Phone: +1 (336) 716-7651
• EMail: ctegeler@wakehealth.edu

Publications of Results:

Lee SW, Gerdes L, Tegeler CL, Shaltout HA, Tegeler CH. A bihemispheric autonomic model for traumatic stress effects on health and behavior. Front Psychol. 2014 Aug 1;5:843. doi: 10.3389/fpsyg.2014.00843. eCollection 2014.

Tegeler CH, Tegeler CL, Cook JF, Lee SW, Pajewski NM. Reduction in menopause-related symptoms associated with use of a noninvasive neurotechnology for autocalibration of neural oscillations. Menopause. 2015 Jun;22(6):650-5. doi: 10.1097/GME.0000000000000422.

Tegeler CH, Shaltout HA, Tegeler CL, Gerdes L, Lee SW. Rightward dominance in temporal high-frequency electrical asymmetry corresponds to higher resting heart rate and lower baroreflex sensitivity in a heterogeneous population. Brain Behav. 2015 Jun;5(6):e00343. doi: 10.1002/brb3.343. Epub 2015 May 1.

Fortunato JE, Tegeler CL, Gerdes L, Lee SW, Pajewski NM, Franco ME, Cook JF, Shaltout HA, Tegeler CH. Use of an allostatic neurotechnology by adolescents with postural orthostatic tachycardia syndrome (POTS) is associated with improvements in heart rate variability and changes in temporal lobe electrical activity. Exp Brain Res. 2016 Mar;234(3):791-8. doi: 10.1007/s00221-015-4499-y. Epub 2015 Dec 8.

Tegeler CH, Tegeler CL, Cook JF, Lee SW, Gerdes L, Shaltout HA, Miles CM, Simpson SL. A Preliminary Study of the Effectiveness of an Allostatic, Closed-Loop, Acoustic Stimulation Neurotechnology in the Treatment of Athletes with Persisting Post-concussion Symptoms. Sports Med Open. 2016 Dec;2(1):39. doi: 10.1186/s40798-016-0063-y. Epub 2016 Sep 14.

Other Publications:

Gerdes L, Gerdes P, Lee SW, H Tegeler C. HIRREM: a noninvasive, allostatic methodology for relaxation and auto-calibration of neural oscillations. Brain Behav. 2013 Mar;3(2):193-205. doi: 10.1002/brb3.116. Epub 2013 Jan 14.

Tegeler CH, Kumar SR, Conklin D, Lee SW, Gerdes L, Turner DP, Tegeler CL, C Fidali B, Houle TT. Open label, randomized, crossover pilot trial of high-resolution, relational, resonance-based, electroencephalic mirroring to relieve insomnia. Brain Behav. 2012 Nov;2(6):814-24. doi: 10.1002/brb3.101. Epub 2012 Oct 28.

Tegeler CH, Lee SW, Shaltout HA. Significance of right anterior insula activity for mental health intervention. JAMA Psychiatry. 2014 Mar;71(3):336. doi: 10.1001/jamapsychiatry.2013.3507. No abstract available.

Gerdes L, Tegeler CH, Lee SW. A groundwork for allostatic neuro-education. Front Psychol. 2015 Aug 17;6:1224. doi: 10.3389/fpsyg.2015.01224. eCollection 2015.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Tegeler CH, Cook JF, Tegeler CL, Hirsch JR, Shaltout HA, Simpson SL, Fidali BC, Gerdes L, Lee SW. Clinical, hemispheric, and autonomic changes associated with use of closed-loop, allostatic neurotechnology by a case series of individuals with self-reported symptoms of post-traumatic stress. BMC Psychiatry. 2017 Apr 19;17(1):141. doi: 10.1186/s12888-017-1299-x.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT02709369
• Other Study ID Numbers: IRB00017651
• First Submitted: March 4, 2016
• First Posted: March 16, 2016
• Results First Submitted: November 8, 2019
• Results First Posted: December 24, 2019
• Last Update Posted: December 24, 2019