High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia

• Sponsor: Wake Forest University Health Sciences (Other)
• Overall Status: Completed
• CT.gov ID: NCT01971567
• Collaborator: (none)
• Enrollment: 107
• Location: 1
• Arms: 2
• Actual Duration (Months): 40.2
• Patients Per Site Per Month: 2.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether the addition of High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) to usual care will improve insomnia symptoms based on changes in the Insomnia Severity Index at two months following completion of the intervention, compared to placebo plus usual care.

Condition or Disease	Intervention/Treatment	Phase
Insomnia	Device: HIRREM	N/A

Detailed Description

Insomnia is the most prevalent sleep disorder and is associated with significant psychosocial and somatic pathology. Effective noninvasive interventions for insomnia are lacking. High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM), is a noninvasive, brain feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. An open label, randomized, crossover pilot trial showed that HIRREM was safe and effective, with significant benefits for individuals with moderate to severe insomnia, based on differential change with symptoms of insomnia (Insomnia Severity Index, ISI). This study will extend those results in a larger cohort using a single blind, placebo controlled study design.

Study Design

• Study Type: Interventional
• Actual Enrollment: 107 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Treatment
• Official Title: High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia: A Randomized, Placebo-Controlled Clinical Trial
• Actual Study Start Date: Oct 1, 2013
• Actual Primary Completion Date: Dec 12, 2016
• Actual Study Completion Date: Feb 6, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: HIRREM High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time.	Device: HIRREM; Other Names: High-resolution, relational, resonance-based, electroencephalic mirroring Brainwave Optimization
Placebo Comparator: Placebo Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes.	Device: HIRREM; Other Names: High-resolution, relational, resonance-based, electroencephalic mirroring Brainwave Optimization

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in Insomnia Severity Index (ISI) [Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention]

   The ISI is a 7 question, self-reported measure to evaluate symptoms of insomnia, with responses from 0-4 for each question, yielding scores ranging from 0-28. Lower scores represent better outcomes. The primary outcome will be change from enrollment to 8-10 weeks after completion of the intervention.

Secondary Outcome Measures

1. Change From Baseline in Sleep Onset Latency and Wake After Sleep Onset [Baseline and 8-10 weeks after completion of intervention]

   This will be an online daily sleep diary to evaluate the amount and quality of sleep. This allows evaluation of the timing and trajectory of any improvements in sleep, including appreciation of the presence and duration of placebo effects. Measurements of sleep onset latency (SOL) and wake after sleep onset (WASO) were recorded in minutes.

2. Change in Total Sleep Time (TST) [Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention]

   This will be an online daily sleep diary to evaluate the amount and quality of sleep. This allows evaluation of the timing and trajectory of any improvements in sleep, including appreciation of the presence and duration of placebo effects. Participants recorded the total sleep time (TST) they had each night. The outcome indicates the average increase (in hours) of the amount of sleep that each group reported.

3. Change in RestRefresh and SleepQual [Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention]

   This will be an online daily sleep diary to evaluate the amount and quality of sleep. This allows evaluation of the timing and trajectory of any improvements in sleep, including appreciation of the presence and duration of placebo effects. Participants were asked to report a self-rating on how well they felt rested and refreshed (RestRefresh) and to rate the quality of sleep they had (SleepQual). Both questions were rated on a 0 to 4 scale and higher scores denotes better outcomes for each.

4. Change From Baseline in Beck Depression Inventory - II (BDI-II) [Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention]

   Depression will be measured by the Beck Depression Inventory-II (BDI-II). The BDI-II is a 21-item questionnaire with response values of 0-3 for each item, yielding scores ranging from 0-63. Higher scores denotes worse outcomes.

5. Change From Baseline in Beck Anxiety Inventory (BAI) [Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention]

   Anxiety will be measured by the Beck Anxiety Inventory (BAI). The BAI is a 21-item questionnaire with response values from 0-3 for each item, yielding scores ranging from 0-63. Higher scores denotes worse outcomes.

6. Change From Baseline in EQ-5D [Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention]

   Health-related quality of life will be measured by the EQ-5D. The EQ-5D consists of 5 items assessing an individual's current health status (values from 0-2), yielding scores ranging from 0-10. Higher scores denotes worse outcomes.

7. Change in Heart Rate Variability (HRV) [Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention]

   Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system (BIOPAC acquisition system and Acknowledge 4.2 software, Santa Barbara, CA), at 1000 Hz, are analyzed using Nevrokard BRS software (Nevrokard BRS, Medistar, Ljubljana, Slovenia). Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis. Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval (SDNN, milliseconds)and the root mean square of successive beat-to-beat differences in R-R interval duration (rMSSD milliseconds). For calculation of SDNN, the R-R intervals are visually inspected, and data considered as artifact is manually removed.

8. Change in Baroflex Sensitivity (BRS) [8-10 weeks after completion of the intervention]

   Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system at 1000 Hz, are analyzed using Nevrokard BRS software. Analysis is conducted on the first complete 5-minute epoch. Power spectral densities of systolic blood pressure (SBP) and R-R interval (RRI) oscillations are computed by 512 points Fast Fourier Transform (FFT) and integrated over specified frequency ranges (HF: 0.15-0.4 Hz). The square-root of the ratio of RRI's and SBP powers is computed to calculate HF alpha indices, which reflect BRS. The software scans the RRI and SBP records, identifies sequences, and calculates linear correlation between RRI and SBP for each sequence. The mean of all individual regression coefficients (slopes), a measure of sequence BRS, is then calculated for Sequence UP, DOWN and TOTAL (seq ALL).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Moderate to severe clinical insomnia (Insomnia Severity Index score of 15 or higher)

Exclusion Criteria:

• Unable, unwilling, or incompetent to provide informed consent

• Physically unable to come to the study visits

• Known obstructive sleep apnea

• Diagnosed periodic limb movement disorder or known restless legs syndrome

• Known seizure disorder

• Known urinary problem (i.e. benign prostatic hypertrophy) which is the likely cause of the sleep disturbance

• Severe hearing impairment

• Known, or suspected diagnosis of post-traumatic stress disorder (PTSD)

• Known, relevant traumatic brain injury (TBI)

• Ongoing need for treatment with opiate, benzodiazepine, or anti-psychotic medications, anti-depressant medications such as SSRI, SNRI, or tricyclics, and sleep medications such as zolpidem or eszopiclone

• Anticipated and ongoing use of recreational drugs or alcohol

• Lack of internet or smart phone access

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Neurology, Wake Forest School of Medicine	Winston-Salem	North Carolina	United States	27157

Sponsors and Collaborators

• Wake Forest University Health Sciences

Investigators

• Principal Investigator: Charles H. Tegeler, MD, Department of Neurology, Wake Forest School of Medicine

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: Wake Forest University Health Sciences
• ClinicalTrials.gov Identifier: NCT01971567
• Other Study ID Numbers: IRB00024763
• First Posted: Oct 29, 2013
• Last Update Posted: Sep 10, 2018
• Last Verified: Aug 1, 2018

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Wake Forest University Health Sciences: Insomnia; Electroencephalic; Biofeedback; Neural oscillations; Auto calibration; Relaxation
• Additional relevant MeSH terms: Sleep Initiation and Maintenance Disorders

Study Results

Participant Flow

Arm/Group Title	HIRREM	Placebo
Arm/Group Description	High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. HIRREM	Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes. HIRREM
Period Title: Overall Study
STARTED	56	51
COMPLETED	52	49
NOT COMPLETED	4	2

Baseline Characteristics

Arm/Group Title	HIRREM	Placebo	Total
Arm/Group Description	High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. HIRREM	Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes. HIRREM	Total of all reporting groups
Overall Participants	56	51	107
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.4 (15.1)	54.7 (14.8)	53.5 (14.9)
Sex: Female, Male (Count of Participants)
Female	41 73.2%	32 62.7%	73 68.2%
Male	15 26.8%	19 37.3%	34 31.8%
Race/Ethnicity, Customized (Count of Participants)
White	46 82.1%	43 84.3%	89 83.2%
Other	10 17.9%	8 15.7%	18 16.8%
Duration with Sleep Trouble (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	11.1 (12.1)	12.2 (11.3)	11.7 (11.7)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in Insomnia Severity Index (ISI)
Description	The ISI is a 7 question, self-reported measure to evaluate symptoms of insomnia, with responses from 0-4 for each question, yielding scores ranging from 0-28. Lower scores represent better outcomes. The primary outcome will be change from enrollment to 8-10 weeks after completion of the intervention.
Time Frame	Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HIRREM	Placebo
Arm/Group Description	High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. HIRREM	Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes. HIRREM
Measure Participants	56	51
Mean (Standard Error) [units on a scale]	-6.98 (0.74)	-4.94 (0.76)

2. Secondary Outcome

Title	Change From Baseline in Sleep Onset Latency and Wake After Sleep Onset
Description	This will be an online daily sleep diary to evaluate the amount and quality of sleep. This allows evaluation of the timing and trajectory of any improvements in sleep, including appreciation of the presence and duration of placebo effects. Measurements of sleep onset latency (SOL) and wake after sleep onset (WASO) were recorded in minutes.
Time Frame	Baseline and 8-10 weeks after completion of intervention

Outcome Measure Data

Analysis Population Description

Data was not able to be collected for all participants.

Arm/Group Title	HIRREM	Placebo
Arm/Group Description	High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. HIRREM	Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes. HIRREM
Measure Participants	47	39
SOL	-1.00 (0.18)	-0.56 (0.14)
WASO	-28.42 (8.00)	-22.64 (4.73)

3. Secondary Outcome

Title	Change in Total Sleep Time (TST)
Description	This will be an online daily sleep diary to evaluate the amount and quality of sleep. This allows evaluation of the timing and trajectory of any improvements in sleep, including appreciation of the presence and duration of placebo effects. Participants recorded the total sleep time (TST) they had each night. The outcome indicates the average increase (in hours) of the amount of sleep that each group reported.
Time Frame	Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

Data was not able to be collected for all participants.

Arm/Group Title	HIRREM	Placebo
Arm/Group Description	High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. HIRREM	Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes. HIRREM
Measure Participants	47	39
Mean (Standard Error) [hours]	1.15 (0.23)	0.58 (0.17)

4. Secondary Outcome

Title	Change in RestRefresh and SleepQual
Description	This will be an online daily sleep diary to evaluate the amount and quality of sleep. This allows evaluation of the timing and trajectory of any improvements in sleep, including appreciation of the presence and duration of placebo effects. Participants were asked to report a self-rating on how well they felt rested and refreshed (RestRefresh) and to rate the quality of sleep they had (SleepQual). Both questions were rated on a 0 to 4 scale and higher scores denotes better outcomes for each.
Time Frame	Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

Data was not able to be collected for all participants.

Arm/Group Title	HIRREM	Placebo
Arm/Group Description	High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. HIRREM	Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes. HIRREM
Measure Participants	47	39
RestRefresh	0.60 (0.16)	0.54 (0.12)
SleepQual	0.79 (0.16)	0.67 (0.12)

5. Secondary Outcome

Title	Change From Baseline in Beck Depression Inventory - II (BDI-II)
Description	Depression will be measured by the Beck Depression Inventory-II (BDI-II). The BDI-II is a 21-item questionnaire with response values of 0-3 for each item, yielding scores ranging from 0-63. Higher scores denotes worse outcomes.
Time Frame	Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HIRREM	Placebo
Arm/Group Description	High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. HIRREM	Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes. HIRREM
Measure Participants	52	49
Mean (Standard Error) [units on a scale]	-3.76 (0.59)	-2.65 (0.61)

6. Secondary Outcome

Title	Change From Baseline in Beck Anxiety Inventory (BAI)
Description	Anxiety will be measured by the Beck Anxiety Inventory (BAI). The BAI is a 21-item questionnaire with response values from 0-3 for each item, yielding scores ranging from 0-63. Higher scores denotes worse outcomes.
Time Frame	Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

Data not collected for one participant in the placebo group

Arm/Group Title	HIRREM	Placebo
Arm/Group Description	High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. HIRREM	Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes. HIRREM
Measure Participants	52	48
Mean (Standard Error) [units on a scale]	-0.25 (0.10)	-0.25 (0.10)

7. Secondary Outcome

Title	Change From Baseline in EQ-5D
Description	Health-related quality of life will be measured by the EQ-5D. The EQ-5D consists of 5 items assessing an individual's current health status (values from 0-2), yielding scores ranging from 0-10. Higher scores denotes worse outcomes.
Time Frame	Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HIRREM	Placebo
Arm/Group Description	High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. HIRREM	Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes. HIRREM
Measure Participants	52	49
Mean (Standard Error) [units on a scale]	2.73 (1.90)	0.11 (1.94)

8. Secondary Outcome

Title	Change in Heart Rate Variability (HRV)
Description	Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system (BIOPAC acquisition system and Acknowledge 4.2 software, Santa Barbara, CA), at 1000 Hz, are analyzed using Nevrokard BRS software (Nevrokard BRS, Medistar, Ljubljana, Slovenia). Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis. Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval (SDNN, milliseconds)and the root mean square of successive beat-to-beat differences in R-R interval duration (rMSSD milliseconds). For calculation of SDNN, the R-R intervals are visually inspected, and data considered as artifact is manually removed.
Time Frame	Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

Other entries were excluded due to missing or dropped heartbeats and were excluded from the analysis for continuity

Arm/Group Title	HIRREM	Placebo
Arm/Group Description	High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. HIRREM	Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes. HIRREM
Measure Participants	52	47
SDNN	57.28 (1.34)	35.81 (1.77)
rMSSD	53.06 (5.34)	26.86 (2.24)

9. Secondary Outcome

Title	Change in Baroflex Sensitivity (BRS)
Description	Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system at 1000 Hz, are analyzed using Nevrokard BRS software. Analysis is conducted on the first complete 5-minute epoch. Power spectral densities of systolic blood pressure (SBP) and R-R interval (RRI) oscillations are computed by 512 points Fast Fourier Transform (FFT) and integrated over specified frequency ranges (HF: 0.15-0.4 Hz). The square-root of the ratio of RRI's and SBP powers is computed to calculate HF alpha indices, which reflect BRS. The software scans the RRI and SBP records, identifies sequences, and calculates linear correlation between RRI and SBP for each sequence. The mean of all individual regression coefficients (slopes), a measure of sequence BRS, is then calculated for Sequence UP, DOWN and TOTAL (seq ALL).
Time Frame	8-10 weeks after completion of the intervention

Outcome Measure Data

Analysis Population Description

Other entries were excluded due to missing or dropped heartbeats and were excluded from the analysis for continuity

Arm/Group Title	HIRREM	Placebo
Arm/Group Description	High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. HIRREM	Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes. HIRREM
Measure Participants	52	47
HF Alpha	24.78 (2.17)	16.26 (1.73)
Seq ALL	20.36 (2.03)	12.31 (1.09)

Adverse Events

Time Frame	16-18 weeks after completion of the intervention
Arm/Group Title	HIRREM		Placebo
Arm/Group Description	High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. HIRREM		Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes. HIRREM
All Cause Mortality
	HIRREM		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/56 (0%)		0/51 (0%)
Serious Adverse Events
	HIRREM		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/56 (0%)		0/51 (0%)
Other (Not Including Serious) Adverse Events
	HIRREM		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/56 (10.7%)		7/51 (13.7%)
General disorders
Change in sleep	2/56 (3.6%)		2/51 (3.9%)
Head fullness	3/56 (5.4%)		2/51 (3.9%)
Skin and subcutaneous tissue disorders
Skin irritation at scalp sensor site	0/56 (0%)		1/51 (2%)
Social circumstances
Change in emotions or awareness of feelings	1/56 (1.8%)		2/51 (3.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.