HIRREM Developmental Study

Study Overview
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Brief Summary
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The purpose of this study is to explore the functional and physiological effects associated with the use of High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM), as supplemental care, for symptoms of neurological, cardiovascular, and neuropsychological disorders. This is a non-randomized, open label, and unblinded before-and-after trial, evaluating the effect of HIRREM on an objective, physiological common denominator (heart rate variability, HRV), across a variety of relevant conditions, as well as changes in clinical symptoms inventories, to generate hypotheses and pilot data for investigation in future proposals.

Official Title
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Functional and Physiological Effects of High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) for Neurological, Cardiovascular and Psychophysiological Disorders

Conditions
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Sleep Initiation and Maintenance Disorders, Post-Traumatic Stress Disorder, Hot Flashes, Traumatic Brain Injury, Post Concussion Symptoms, Anxiety, Headache

Intervention / Treatment
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* Device: HIRREM


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female adults and children aged 11 years and older. Subjects who are over the age of 18 must be able to give informed consent. Children must be able to sign an assent form and have a signed parental permission form. Subjects must have the ability to comply with basic instructions and be able to sit still comfortably with the sensor leads attached. Subjects previously diagnosed with a neurologic, cardiovascular, or psychophysiological disease such as attention deficit hyperactivity disorder, Asperger Syndrome, chronic pain, dyslexia, depression, insomnia, migraines, anxiety, PTSD, substance abuse disorder, traumatic brain injury, and others. Exclusion Criteria: Subjects who fail to meet inclusion criteria. Subjects who are unable, unwilling, or incompetent to provide informed consent, assent and/or parental permission. Subjects physically unable to come to the study visits. Subjects with a known seizure disorder. Subjects with severe bilateral hearing impairment (HIRREM requires the use of headphones). Subjects receiving ongoing treatment with opiate, benzodiazepine, anti-psychotic or sleep medications, as well as some anti-depressants or stimulants, except those cases deemed acceptable by the principal investigator. Subjects with anticipated and ongoing use of recreational drugs except when deemed acceptable by the principal investigator.

Ages Eligible for Study
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Minimum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active HIRREM<br>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. | Device: HIRREM<br>* HIRREM is a noninvasive, closed-loop, allostatic, acoustic stimulation neuro-technology to facilitate recipient-unique relaxation, auto-calibration, and self-optimization of cortical neural oscillations by reflecting auditory tones in near real time. After an initial HIRREM assessment, evaluating patterns of brain electrical rhythms, subjects get a series of 90-120 minute HIRREM sessions, including 5 to 9 individualized protocols. A protocol is a combination of sensor montage and specific software design, during which dominant brain frequencies, recorded at high spectral resolutions, are translated to audible tones, and reflected back via earphones with as little as 8 milliseconds delay. Protocols are received sitting or reclining in a chair, some with eyes open, others eyes closed.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart Rate Variability Standard Deviation of NN Intervals (SDNN) | Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval | Baseline/Enrollment visit | 
| Heart Rate Variability (SDNN) | Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval | Up to 2 weeks after the intervention is completed | 
| Baroreflex Sensitivity High Frequency (HF) Alpha | Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software. | Baseline/Enrollment visit | 
| Baroreflex Sensitivity High Frequency (HF) Alpha | Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software. | Up to two weeks after the intervention is completed | 
| Baroreflex Sensitivity Sequence Up | Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software. | Baseline/Enrollment visit | 
| Baroreflex Sensitivity Sequence Up | Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software. | Up to two weeks after the intervention is completed | 
| Baroreflex Sensitivity Sequence Down | Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software. | Baseline/Enrollment visit | 
| Baroreflex Sensitivity Sequence Down | Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software. | Up to two weeks after the intervention is completed | 
| Baroreflex Sensitivity Sequence All | Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software. | Baseline/Enrollment visit | 
| Baroreflex Sensitivity Sequence All | Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software. | Up to 2 weeks after the intervention is completed | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Center for Epidemiologic Studies Depression Scale (CES-D) | 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. | enrollment visit/baseline | 
| Center for Epidemiologic Studies Depression Scale (CES-D) | 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. | 1-2 weeks after intervention is completed | 
| Center for Epidemiologic Studies Depression Scale (CES-D) | 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. | 4-8 weeks after completion of the intervention | 
| Euro Quality of Life--Five Dimension (EQ-5D) | 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. | enrollment visit/baseline | 
| Euro Quality of Life--Five Dimension (EQ-5D) | 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. | 1-2 weeks after the intervention is completed | 
| Euro Quality of Life--Five Dimension (EQ-5D) | 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. | 4-8 weeks after completion of the intervention | 
| Generalized Anxiety Disorder-7 (GAD-7) | 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. | enrollment visit/baseline | 
| Generalized Anxiety Disorder-7 (GAD-7) | 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. | 1-2 weeks after the intervention is completed | 
| Generalized Anxiety Disorder-7 (GAD-7) | 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. | 4-8 weeks after completion of the intervention | 
| Insomnia Severity Index (ISI) | 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. | enrollment visit/baseline | 
| Insomnia Severity Index (ISI) | 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. | 1-2 weeks after the intervention is completed | 
| Insomnia Severity Index (ISI) | 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. | 4-8 weeks after completion of the intervention | 
| Posttraumatic Stress Disorder Checklist (PCL-C) | 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. | enrollment visit/baseline | 
| Posttraumatic Stress Disorder Checklist (PCL) | 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. | 1-2 weeks after the intervention is completed | 
| Posttraumatic Stress Disorder Checklist (PCL) | 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. | 4-8 weeks after completion of the intervention | 
| Rivermead Post-Concussion Symptoms Questionnaire (RPQ) | 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. | enrollment visit/baseline | 
| Rivermead Post-Concussion Symptoms Questionnaire (RPQ) | 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. | 1-2 weeks after the intervention is completed | 
| Rivermead Post-Concussion Symptoms Questionnaire (RPQ) | 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. | 4-8 weeks after completion of the intervention | 
| Drop Stick Reaction Testing | 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. | enrollment visit/baseline | 
| Drop Stick Reaction Testing | 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. | 1-2 weeks after the intervention is completed | 
| Drop Stick Reaction Testing | 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. | 4-8 weeks after completion of the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neuro-technology, Closed-loop, Acoustic stimulation, Allostatic, heart rate variability, baroreflex sensitivity, traumatic brain injury, sports concussion, PTSD, hot flashes, headache, insomnia, HIRREM