HIRREM Developmental Study

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

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.

Study Overview

• Status: Completed
• Conditions: Sleep Initiation and Maintenance Disorders; Hot Flashes; Anxiety; Headache; Traumatic Brain Injury; Post-Traumatic Stress Disorder; Post Concussion Symptoms
• Intervention / Treatment: Device: HIRREM

• Study Type: Interventional
• Enrollment (Actual): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Department of Neurology, Wake Forest School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 11 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Active HIRREM; 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; 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.

What is the study measuring?

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

Other 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	4-8 weeks after completion of the intervention
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.	4-8 weeks after completion of the intervention
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.	4-8 weeks after completion of the intervention
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.	4-8 weeks after completion of the intervention
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.	4-8 weeks after completion of the intervention

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences

Publications and helpful links

General 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): August 23, 2011
• Primary Completion (Actual): October 25, 2018
• Study Completion (Actual): October 25, 2018

Study Registration Dates

• First Submitted: March 4, 2016
• First Submitted That Met QC Criteria: March 9, 2016
• First Posted (Estimate): March 16, 2016

Study Record Updates

• Last Update Posted (Actual): December 24, 2019
• Last Update Submitted That Met QC Criteria: December 11, 2019
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: PTSD; insomnia; traumatic brain injury; headache; hot flashes; heart rate variability; baroreflex sensitivity; Closed-loop; HIRREM; Neuro-technology; Acoustic stimulation; Allostatic; sports concussion
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Pain; Neurologic Manifestations; Wounds and Injuries; Craniocerebral Trauma; Trauma, Nervous System; Trauma and Stressor Related Disorders; Brain Concussion; Head Injuries, Closed; Wounds, Nonpenetrating; Disease; Brain Injuries; Sleep Initiation and Maintenance Disorders; Stress Disorders, Traumatic; Stress Disorders, Post-Traumatic; Brain Injuries, Traumatic; Headache; Hot Flashes; Post-Concussion Syndrome
• Other Study ID Numbers: IRB00017651

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: Data will be shared in publications and presentations. No plan to formally make individual participant data available for this exploratory study

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes