Trial Outcomes & Findings for HIRREM in Military Personnel (NCT NCT03230890)

NCT ID: NCT03230890

Last Updated: 2023-08-14

Results Overview

The PTSD Checklist (PCL) - Military (M) is a symptom checklist to measure stress severity due to a traumatic experience in military settings. The PCL-M measures the American Psychiatric Association's Diagnostic and statistical manual of mental disorders (DSM-IV) of PTSD symptoms based on traumatic life experience. Seventeen items are rated on a Likert scale from 1 (not at all) to 5 (extremely), with a total score ranging from 17 to 85. Higher scores suggest more PTSD symptoms. Primary outcome for this pilot study will be change in PCL-M score from baseline to the immediate post-intervention in-person data collection at the completion of the HIRREM intervention (up to 12 days later).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 32 participants
• Primary outcome timeframe: Data is collected at baseline and immediately following completion of the HIRREM intervention (up to 12 days later)
• Results posted on: 2023-08-14

Participant Flow

Participant milestones

Measure	HIRREM This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.
Overall Study STARTED	32
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

HIRREM in Military Personnel

Baseline characteristics by cohort

Measure	HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	32 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	40.72 years STANDARD_DEVIATION 6.40 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	31 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	26 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	5 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants
Region of Enrollment United States	32 participants n=5 Participants

PRIMARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the HIRREM intervention (up to 12 days later)

The PTSD Checklist (PCL) - Military (M) is a symptom checklist to measure stress severity due to a traumatic experience in military settings. The PCL-M measures the American Psychiatric Association's Diagnostic and statistical manual of mental disorders (DSM-IV) of PTSD symptoms based on traumatic life experience. Seventeen items are rated on a Likert scale from 1 (not at all) to 5 (extremely), with a total score ranging from 17 to 85. Higher scores suggest more PTSD symptoms. Primary outcome for this pilot study will be change in PCL-M score from baseline to the immediate post-intervention in-person data collection at the completion of the HIRREM intervention (up to 12 days later).

Outcome measures

Measure

HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in PCL-M Score From Baseline to 12 Days

-12.88 score on a scale Standard Deviation 9.11

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

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 more depressive symptomatology. Secondary outcome with the CES-D will be analyzed for change from baseline to the immediate post-HIRREM in person data collection.

Outcome measures

Measure

HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Center for Epidemiologic Studies Depression Scale (CES-D) Score From Baseline to 12 Days

-13.69 units on a scale Standard Deviation 9.24

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

The severity of insomnia symptoms is measured using the ISI with each data collection visit. The ISI is a 7 question measure, with responses from 0-4 for each question, yielding scores ranging from 0-28. Higher scores indicate the strength of the insomnia severity. Secondary outcome with the ISI will be analyzed for change from baseline to the immediate post-HIRREM in person data collection.

Outcome measures

Measure

HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Insomnia Severity Index (ISI) Score From Baseline to 12 Days

-6.31 score on a scale Standard Deviation 5.03

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

The Generalized Anxiety Disorder-7 (GAD-7) is a seven item screening tool for anxiety that is widely used in primary care. Each item is rated from 0 (not at all) to 3 (nearly every day). Scores range from 0 to 21 with higher scores suggesting more anxiety. Secondary outcome with the GAD-7 will be analyzed for change from baseline to the immediate post-HIRREM in person data collection.

Outcome measures

Measure

HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Generalized Anxiety Disorder-7 (GAD-7) Score From Baseline to 12 Days

-6.69 score on a scale Standard Deviation 4.72

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

Population: Two participants did not have history of concussion and did not complete measure.

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 (least to greatest symptom severity). Items are compared to levels before the head injury and are reported as a 24 hour recall. Secondary outcome with the RPQ will be analyzed for change from baseline to the immediate post-HIRREM in person data collection.

Outcome measures

Measure

HIRREM n=30 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Rivermead Post-Concussion Symptoms Questionnaire (RPQ) Score From Baseline to 12 Days

-10.70 score on a scale Standard Deviation 11.71

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

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. Secondary outcome with the EQ-5D will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Global health rating question is reported (0-100, with 100 being in the best health possible).

Outcome measures

Measure

HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in EQ-5D Score From Baseline to 12 Days

9.59 score on a scale Standard Deviation 12.35

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

Secondary autonomic outcome with heart rate variability will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Heart rate variability is measured in the time domain as standard deviation beat-to-beat interval (SDNN, milliseconds). For calculation of SDNN, the R-R intervals are visually inspected, and data considered as artifact is manually removed. Higher SDNN values suggest better autonomic regulation.

Outcome measures

Measure

HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Heart Rate Variability Measure of SDNN From Baseline to 12 Days

9.43 ms Standard Deviation 17.43

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

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 Baroreflex Sensitivity (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. Evaluation includes analysis for measures of spontaneous baroreflex sensitivity (BRS), in the frequency domain as high frequency (HF) alpha index (ms2). Secondary autonomic outcome with BRS will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Higher values in HF alpha suggest better autonomic regulation.

Outcome measures

Measure

HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Baroreflex Sensitivity HF Alpha From Baseline to 12 Days

9.43 ms2 Standard Deviation 12.05

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

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 Baroreflex Sensitivity (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. Evaluation includes analysis for measures of spontaneous baroreflex sensitivity (BRS), in the time domain as frequency domain as BRS Sequence Up (ms/mmHg). Secondary autonomic outcome with BRS will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Higher values in Sequence Up suggest better autonomic regulation.

Outcome measures

Measure

HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Baroreflex Sensitivity Sequence Up From Baseline to 12 Days

7.46 ms/mmHg Standard Deviation 12.33

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

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 Baroreflex Sensitivity (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. Evaluation includes analysis for measures of spontaneous baroreflex sensitivity (BRS), in the time domain as frequency domain as BRS Sequence Down (ms/mmHg). Secondary autonomic outcome with BRS will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Higher values in Sequence Down suggest better autonomic regulation.

Outcome measures

Measure

HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Baroreflex Sensitivity Sequence Down From Baseline to 12 Days

5.56 ms/mmHg Standard Deviation 9.16

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

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 Baroreflex Sensitivity (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. Evaluation includes analysis for measures of spontaneous baroreflex sensitivity (BRS), in the time domain as frequency domain as BRS Sequence All (ms/mmHg). Secondary autonomic outcome with BRS will be analyzed for change from baseline to the immediate post-HIRREM in person data collection. Higher values in Sequence All suggest better autonomic regulation.

Outcome measures

Measure

HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Baroreflex Sensitivity Sequence All From Baseline to 12 Days

5.75 ms/mmHg Standard Deviation 8.21

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

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. Secondary functional outcome with drop-stick reaction time will be analyzed for changes in distance from baseline to the in person data collection immediately after completion of the intervention. A lower average indicates a faster reaction time.

Outcome measures

Measure

HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Drop Stick Reaction Time From Baseline to 12 Days

-3.86 cm Standard Deviation 6.64

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

Grip strength will evaluated using a hydraulic hand dynamometer (Baseline Hydraulic Hand Dynamometer, ranges from 0 to 300 lbs). Both right and left hand will be evaluated, and the greatest force generated during three trials will be used for analysis. A higher score indicates stronger grip strength.

Outcome measures

Measure	HIRREM n=32 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.
Change in Grip Strength From Baseline to 12 Days Right Hand	1.74 lbs Standard Deviation 13.25
Change in Grip Strength From Baseline to 12 Days Left Hand	1.94 lbs Standard Deviation 11.19

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

Population: Due to funding limitations, only 18 received fMRI scans.

Anatomical and physiological brain imaging will be performed during a 1-hour imaging session at baseline and immediately following completion of the intervention. This will include imaging sequences such as high resolution structural scans. Brain network data will be collected using blood oxygenation level dependent (BOLD) scans. These scans will be collected under various states such as at rest. All images will be acquired using a 3 Tesla Siemens MRI scanner. Whole-brain network connectivity will be assessed using blood oxygenation level dependent (BOLD) imaging. Unit of measure is percentage of BOLD signal change. Community structure will be determined for each participant pre- and post-intervention. This project will focus on the community including the Default Mode Network (DMN). Participant strength of the community structure will be determined of the DMN. Permutation analysis will be used to evaluate significant pattern change in specific networks.

Outcome measures

Measure

HIRREM n=18 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Functional MRI From Baseline to 12 Days

-0.012 % blood oxygenation level dep (BOLD) Standard Deviation 0.034

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

Population: Due to funding limitations, only 15 people received biomarker measures. One sample was unable to be used, so n=14 is presented.

Blood for a panel of biomarkers for stress will be collected at enrollment, and after completion of the intervention. The panel includes Ang II, Ang 1-7, Epinephrine, Norepinephrine, C-reactive protein, Vasopressin, IL-1, IL-6, and IL-10.

Outcome measures

Measure	HIRREM n=14 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.
Change in Blood Biomarkers for Stress and Inflammation Score From Baseline to 12 Days Ang II (pg/ml)	-0.50 pg/ml Standard Deviation 23.17
Change in Blood Biomarkers for Stress and Inflammation Score From Baseline to 12 Days Ang 1-7 (pg/ml)	5.11 pg/ml Standard Deviation 16.94
Change in Blood Biomarkers for Stress and Inflammation Score From Baseline to 12 Days Epinephrine (pg/ml)	-5.87 pg/ml Standard Deviation 20.66
Change in Blood Biomarkers for Stress and Inflammation Score From Baseline to 12 Days Norepinephrine (pg/ml)	-29.98 pg/ml Standard Deviation 165.88
Change in Blood Biomarkers for Stress and Inflammation Score From Baseline to 12 Days Vasopressin (pg/ml)	-0.19 pg/ml Standard Deviation 0.77
Change in Blood Biomarkers for Stress and Inflammation Score From Baseline to 12 Days IL-1 (pg/ml)	-0.20 pg/ml Standard Deviation 0.07
Change in Blood Biomarkers for Stress and Inflammation Score From Baseline to 12 Days IL-6 (pg/ml)	-0.06 pg/ml Standard Deviation 0.21
Change in Blood Biomarkers for Stress and Inflammation Score From Baseline to 12 Days IL-10 (pg/ml)	-0.09 pg/ml Standard Deviation 0.22

SECONDARY outcome

Timeframe: Salivary biomarker for stress will be obtained at baseline and immediately following completion of the intervention (up to 12 days)

Population: One participant had a bad file for salivary amylase (n=14).

Saliva for salivary biomarker Cortisol, for stress, will be collected at enrollment, and after completion of the intervention.

Outcome measures

Measure

HIRREM n=14 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Salivary Biomarker Cortisol for Stress From Baseline to 12 Days

0.04 ug/dl Standard Deviation 0.13

SECONDARY outcome

Timeframe: Blood for epigenetic markers will be obtained at baseline and immediately following completion of the intervention (up to 12 days)

Population: Only a subset of the main cohort had this testing done due to limited funds.

DNA will be isolated from whole blood, collected in yellow-top Vacutainer tubes (ACD as the preservative), using the AutoPure LS system in the Genomics Center Core lab. DNA will be bisulfite-converted using the EZ DNA Methylation Gold kit (Zymo, Irvine, CA). To quantify DNA methylation at each site, investigators will use the HumanMethylationEPIC450 BeadChip (Illumina, Inc.). The methylation proportion for each site (beta value) is based on the ratio of the fluorescence intensity of the methylated versus the combined methylated & unmethylated probes, & will be determined with GenomeStudio (Illumina, Inc.). Ratio of 0 equals no methylation & ratio of 1 equals total (100%) methylation." Effects of DNA methylation for a specific site are dependent on function of the regulated gene(s). For some genes, increased level methylation from the intervention may be beneficial, while for others an increased level may be detrimental. There is no universal way to interpret change in DNA methylation.

Outcome measures

Measure

HIRREM n=8 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Epigenetic Markers From Baseline to 12 Days

-.00038 ratio of methylation Standard Deviation 0.006003

SECONDARY outcome

Timeframe: Sleep diary data will be collected daily via online access from baseline to a month following completion of intervention (up to 42 days)

Population: Due to initial funding, only the first 18 participants received the sleep diary.

An online daily sleep diary to calculate sleep latency will be maintained from baseline, through the one month post-intervention remote data collection (roughly 42 days). Sleep latency is reported in minutes and a smaller score suggests falling asleep faster.

Outcome measures

Measure

HIRREM n=18 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in Sleep Latency Score From Baseline to 42 Days

36.01 minutes Standard Deviation 27.24

SECONDARY outcome

Timeframe: Data is collected at baseline and immediately following completion of the intervention (up to 12 days later)

Population: Due to funding limitations, only 15 people received biomarker measures. One sample was unable to be used, so n=14 is presented.

Blood for biomarker C-reactive protein for stress will be collected at enrollment, and after completion of the intervention.

Outcome measures

Measure

HIRREM n=14 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Change in C-reactive Protein for Stress and Inflammation Score From Baseline to 12 Days

-0.10 mg/dl Standard Deviation 0.19

SECONDARY outcome

Timeframe: Salivary biomarker Alpha-Amylase for stress will be obtained at baseline and immediately following completion of the intervention (up to 12 days)

Population: One participant had a bad file for salivary amylase (n=14).

Saliva for salivary biomarker Alpha-Amylase, for stress, will be collected at enrollment, and after completion of the intervention.

Outcome measures

Measure

HIRREM n=14 Participants This is the intervention, treatment arm that all participants receive in this open label, single arm trial. The intervention is High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM). HIRREM: HIRREM is a closed-loop, allostatic, acoustic stimulation neurotechnology intended to support auto-calibration of neural oscillations. The core technology is commercially available as a technique for relaxation. Scalp sensors monitor brain frequencies and amplitudes, and in real time, software algorithms translate specific frequencies into audible tones of varying pitch. These are reflected via earbuds in as little as 4-8 milliseconds. The in-office intervention for this study is administered as a series of up to twenty four, typically 1.5-2 hours sessions, comprised of 4-10 protocols (some eyes open, some eyes closed), lasting 6-40 minutes each, working at different scalp locations. Sessions are received over 12 days. Two sessions can be done in a half day. The intervention is received while comfortably seated in a zero gravity chair.

Salivary Biomarker for Stress From Baseline to 12 Days

15.00 (U/ml) Standard Deviation 16.66

Adverse Events

HIRREM

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Charles H. Tegeler, MD

Atrium Health Wake Forest Baptist

Phone: 336-716-9447

Email: BBRP@wakehealth.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place