We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

HIRREM Developmental Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02709369
Recruitment Status : Completed
First Posted : March 16, 2016
Results First Posted : December 24, 2019
Last Update Posted : December 24, 2019
Sponsor:
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Tracking Information
First Submitted Date  ICMJE March 4, 2016
First Posted Date  ICMJE March 16, 2016
Results First Submitted Date  ICMJE November 8, 2019
Results First Posted Date  ICMJE December 24, 2019
Last Update Posted Date December 24, 2019
Actual Study Start Date  ICMJE August 23, 2011
Actual Primary Completion Date October 25, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 11, 2019)
  • Heart Rate Variability Standard Deviation of NN Intervals (SDNN) [ Time Frame: Baseline/Enrollment visit ]
    Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval
  • Heart Rate Variability (SDNN) [ Time Frame: Up to 2 weeks after the intervention is completed ]
    Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval
  • Baroreflex Sensitivity High Frequency (HF) Alpha [ Time Frame: Baseline/Enrollment visit ]
    Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
  • Baroreflex Sensitivity High Frequency (HF) Alpha [ Time Frame: Up to two weeks after the intervention is completed ]
    Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
  • Baroreflex Sensitivity Sequence Up [ Time Frame: Baseline/Enrollment visit ]
    Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
  • Baroreflex Sensitivity Sequence Up [ Time Frame: Up to two weeks after the intervention is completed ]
    Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
  • Baroreflex Sensitivity Sequence Down [ Time Frame: Baseline/Enrollment visit ]
    Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
  • Baroreflex Sensitivity Sequence Down [ Time Frame: Up to two weeks after the intervention is completed ]
    Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
  • Baroreflex Sensitivity Sequence All [ Time Frame: Baseline/Enrollment visit ]
    Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
  • Baroreflex Sensitivity Sequence All [ Time Frame: Up to 2 weeks after the intervention is completed ]
    Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Original Primary Outcome Measures  ICMJE
 (submitted: March 9, 2016)
  • Heart rate variability [ Time Frame: Data used for analysis of primary outcome is collected at the enrollment visit, and 1-2 weeks after the intervention is completed. ]
    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). For calculation of SDNN, the R-R intervals are visually inspected, and data considered as artifact is manually removed. The primary outcomes will be analysis for change from baseline to post-intervention, 1-2 weeks after intervention is completed.
  • Baroreflex Sensitivity [ Time Frame: Data used for analysis of primary outcome is collected at the enrollment visit, and 1-2 weeks after the intervention is completed. ]
    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, in the frequency domain as high frequency (HF) alpha index (ms2), and in the time domain as Sequence BRS (Up, Down and All, ms/mmHg). The primary outcomes will be analysis for change from baseline to post-intervention, 1-2 weeks after intervention is completed.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: December 11, 2019)
  • Center for Epidemiologic Studies Depression Scale (CES-D) [ Time Frame: enrollment visit/baseline ]
    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.
  • Center for Epidemiologic Studies Depression Scale (CES-D) [ Time Frame: 1-2 weeks after intervention is completed ]
    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.
  • Center for Epidemiologic Studies Depression Scale (CES-D) [ Time Frame: 4-8 weeks after completion of the intervention ]
    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.
  • Euro Quality of Life--Five Dimension (EQ-5D) [ Time Frame: enrollment visit/baseline ]
    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.
  • Euro Quality of Life--Five Dimension (EQ-5D) [ Time Frame: 1-2 weeks after the intervention is completed ]
    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.
  • Euro Quality of Life--Five Dimension (EQ-5D) [ Time Frame: 4-8 weeks after completion of the intervention ]
    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.
  • Generalized Anxiety Disorder-7 (GAD-7) [ Time Frame: enrollment visit/baseline ]
    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.
  • Generalized Anxiety Disorder-7 (GAD-7) [ Time Frame: 1-2 weeks after the intervention is completed ]
    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.
  • Generalized Anxiety Disorder-7 (GAD-7) [ Time Frame: 4-8 weeks after completion of the intervention ]
    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.
  • Insomnia Severity Index (ISI) [ Time Frame: enrollment visit/baseline ]
    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.
  • Insomnia Severity Index (ISI) [ Time Frame: 1-2 weeks after the intervention is completed ]
    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.
  • Insomnia Severity Index (ISI) [ Time Frame: 4-8 weeks after completion of the intervention ]
    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.
  • Posttraumatic Stress Disorder Checklist (PCL-C) [ Time Frame: enrollment visit/baseline ]
    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.
  • Posttraumatic Stress Disorder Checklist (PCL) [ Time Frame: 1-2 weeks after the intervention is completed ]
    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.
  • Posttraumatic Stress Disorder Checklist (PCL) [ Time Frame: 4-8 weeks after completion of the intervention ]
    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.
  • Rivermead Post-Concussion Symptoms Questionnaire (RPQ) [ Time Frame: enrollment visit/baseline ]
    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.
  • Rivermead Post-Concussion Symptoms Questionnaire (RPQ) [ Time Frame: 1-2 weeks after the intervention is completed ]
    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.
  • Rivermead Post-Concussion Symptoms Questionnaire (RPQ) [ Time Frame: 4-8 weeks after completion of the intervention ]
    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.
  • Drop Stick Reaction Testing [ Time Frame: enrollment visit/baseline ]
    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.
  • Drop Stick Reaction Testing [ Time Frame: 1-2 weeks after the intervention is completed ]
    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.
  • Drop Stick Reaction Testing [ Time Frame: 4-8 weeks after completion of the intervention ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: March 9, 2016)
  • Center for Epidemiologic Studies Depression Scale (CES-D) [ Time Frame: Data used for analysis of secondary outcomes is collected at the enrollment visit, 1-2 weeks after the intervention is completed, and 4-8 weeks after completion of the intervention. ]
    The CES-D is a 20-item survey assessing affective depressive symptomatology to screen for risk of depression38. Scores range from 0-60, with a score of 16 commonly used as a clinically relevant cut-off. Secondary outcomes will be analyzed for change from baseline to 1-2 weeks after completion of the intervention, and changes from baseline to 4-8 weeks after completion of the intervention.
  • EQ-5D [ Time Frame: Data used for analysis of secondary outcomes is collected at the enrollment visit, 1-2 weeks after the intervention is completed, and 4-8 weeks after completion of the intervention. ]
    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 outcomes will be analyzed for changes from baseline to 1-2 weeks after completion of the intervention, and change from baseline to 4-8 weeks after completion of the intervention.
  • Generalized Anxiety Disorder-7 (GAD-7) [ Time Frame: Data used for analysis of secondary outcomes is collected at the enrollment visit, 1-2 weeks after the intervention is completed, and 4-8 weeks after completion of the intervention. ]
    The Generalized Anxiety Disorder-7 (GAD-7) is a seven item screening tool for anxiety that is widely used in primary care. Secondary outcomes will be analyzed for changes from baseline to 1-2 weeks after completion of the intervention, and change from baseline to 4-8 weeks after completion of the intervention.
  • Insomnia Severity Index (ISI) [ Time Frame: Data used for analysis of secondary outcomes is collected at the enrollment visit, 1-2 weeks after the intervention is completed, and 4-8 weeks after completion of the intervention. ]
    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. Secondary outcomes will be analyzed for changes from baseline to 1-2 weeks after completion of the intervention, and change from baseline to 4-8 weeks after completion of the intervention.
  • PCL [ Time Frame: Data used for analysis of secondary outcomes is collected at the enrollment visit, 1-2 weeks after the intervention is completed, and 4-8 weeks after completion of the intervention. ]
    The PTSD Checklist (PCL) - Civilian (C) and Military (M) is a symptom checklist to measure stress severity due to a traumatic experience, in civilian or military settings, respectively. The PCL measures the American Psychiatric Association's Diagnostic and statistical manual of mental disorders (DSM-IV) Criteria B, C, & D of PTSD symptoms based on traumatic life experience. Seventeen items are rated on a Likert scale with a composite score range of 17 to 85. Secondary outcomes will be analyzed for changes from baseline to 1-2 weeks after completion of the intervention, and change from baseline to 4-8 weeks after completion of the intervention.
  • Rivermead Post-Concussion Symptoms Questionnaire (RPQ) [ Time Frame: Data used for analysis of secondary outcomes is collected at the enrollment visit, 1-2 weeks after the intervention is completed, and 4-8 weeks after completion of the intervention. ]
    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 outcomes will be analyzed for changes from baseline to 1-2 weeks after completion of the intervention, and change from baseline to 4-8 weeks after completion of the intervention.
  • Drop stick reaction time [ Time Frame: Data used for analysis of secondary outcomes is collected at the enrollment visit, 1-2 weeks after the intervention is completed, and 4-8 weeks after completion of the intervention. ]
    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 outcomes will be analyzed for changes from baseline to 1-2 weeks after completion of the intervention, and change from baseline to 4-8 weeks after completion of the intervention.
Current Other Pre-specified Outcome Measures
 (submitted: December 11, 2019)
  • Heart Rate Variability Standard Deviation of NN Intervals (SDNN) [ Time Frame: 4-8 weeks after completion of the intervention ]
    Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval
  • Baroreflex Sensitivity High Frequency (HF) Alpha [ Time Frame: 4-8 weeks after completion of the intervention ]
    Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
  • Baroreflex Sensitivity Sequence Up [ Time Frame: 4-8 weeks after completion of the intervention ]
    Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
  • Baroreflex Sensitivity Sequence Down [ Time Frame: 4-8 weeks after completion of the intervention ]
    Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
  • Baroreflex Sensitivity Sequence All [ Time Frame: 4-8 weeks after completion of the intervention ]
    Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis using Nevrokard Baroreflex Sensitivity (BRS) software.
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE HIRREM Developmental Study
Official Title  ICMJE Functional and Physiological Effects of High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) for Neurological, Cardiovascular and Psychophysiological Disorders
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Sleep Initiation and Maintenance Disorders
  • Anxiety
  • Post-Traumatic Stress Disorder
  • Hot Flashes
  • Headache
  • Traumatic Brain Injury
  • Post Concussion Symptoms
Intervention  ICMJE 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.
Study Arms  ICMJE 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.
Intervention: Device: HIRREM
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 24, 2018)
300
Original Estimated Enrollment  ICMJE
 (submitted: March 9, 2016)
250
Actual Study Completion Date  ICMJE October 25, 2018
Actual Primary Completion Date October 25, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 11 Years and older   (Child, Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02709369
Other Study ID Numbers  ICMJE IRB00017651
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Data will be shared in publications and presentations. No plan to formally make individual participant data available for this exploratory study
Current Responsible Party Wake Forest University Health Sciences
Original Responsible Party Charles Tegeler, Wake Forest University Health Sciences, Professor of Neurology
Current Study Sponsor  ICMJE Wake Forest University Health Sciences
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Charles H Tegeler, MD Wake Forest University Health Sciences
PRS Account Wake Forest University Health Sciences
Verification Date November 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP