Back to resultsHigh-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia
Primary Purpose
Insomnia
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
HIRREM
Sponsored by
About this trial
This is an interventional treatment trial for Insomnia focused on measuring Insomnia, Electroencephalic, Biofeedback, Neural oscillations, Auto calibration, Relaxation
Eligibility Criteria
Inclusion Criteria:
- Moderate to severe clinical insomnia (Insomnia Severity Index score of 15 or higher)
Exclusion Criteria:
- Unable, unwilling, or incompetent to provide informed consent
- Physically unable to come to the study visits
- Known obstructive sleep apnea
- Diagnosed periodic limb movement disorder or known restless legs syndrome
- Known seizure disorder
- Known urinary problem (i.e. benign prostatic hypertrophy) which is the likely cause of the sleep disturbance
- Severe hearing impairment
- Known, or suspected diagnosis of post-traumatic stress disorder (PTSD)
- Known, relevant traumatic brain injury (TBI)
- Ongoing need for treatment with opiate, benzodiazepine, or anti-psychotic medications, anti-depressant medications such as SSRI, SNRI, or tricyclics, and sleep medications such as zolpidem or eszopiclone
- Anticipated and ongoing use of recreational drugs or alcohol
- Lack of internet or smart phone access
Sites / Locations
- Department of Neurology, Wake Forest School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
HIRREM
Placebo
Arm Description
High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time.
Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes.
Outcomes
Primary Outcome Measures
Change From Baseline in Insomnia Severity Index (ISI)
The ISI is a 7 question, self-reported measure to evaluate symptoms of insomnia, with responses from 0-4 for each question, yielding scores ranging from 0-28. Lower scores represent better outcomes. The primary outcome will be change from enrollment to 8-10 weeks after completion of the intervention.
Secondary Outcome Measures
Change From Baseline in Sleep Onset Latency and Wake After Sleep Onset
This will be an online daily sleep diary to evaluate the amount and quality of sleep. This allows evaluation of the timing and trajectory of any improvements in sleep, including appreciation of the presence and duration of placebo effects. Measurements of sleep onset latency (SOL) and wake after sleep onset (WASO) were recorded in minutes.
Change in Total Sleep Time (TST)
This will be an online daily sleep diary to evaluate the amount and quality of sleep. This allows evaluation of the timing and trajectory of any improvements in sleep, including appreciation of the presence and duration of placebo effects. Participants recorded the total sleep time (TST) they had each night. The outcome indicates the average increase (in hours) of the amount of sleep that each group reported.
Change in RestRefresh and SleepQual
This will be an online daily sleep diary to evaluate the amount and quality of sleep. This allows evaluation of the timing and trajectory of any improvements in sleep, including appreciation of the presence and duration of placebo effects. Participants were asked to report a self-rating on how well they felt rested and refreshed (RestRefresh) and to rate the quality of sleep they had (SleepQual). Both questions were rated on a 0 to 4 scale and higher scores denotes better outcomes for each.
Change From Baseline in Beck Depression Inventory - II (BDI-II)
Depression will be measured by the Beck Depression Inventory-II (BDI-II). The BDI-II is a 21-item questionnaire with response values of 0-3 for each item, yielding scores ranging from 0-63. Higher scores denotes worse outcomes.
Change From Baseline in Beck Anxiety Inventory (BAI)
Anxiety will be measured by the Beck Anxiety Inventory (BAI). The BAI is a 21-item questionnaire with response values from 0-3 for each item, yielding scores ranging from 0-63. Higher scores denotes worse outcomes.
Change From Baseline in EQ-5D
Health-related quality of life will be measured by the EQ-5D. The EQ-5D consists of 5 items assessing an individual's current health status (values from 0-2), yielding scores ranging from 0-10. Higher scores denotes worse outcomes.
Change in Heart Rate Variability (HRV)
Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system (BIOPAC acquisition system and Acknowledge 4.2 software, Santa Barbara, CA), at 1000 Hz, are analyzed using Nevrokard BRS software (Nevrokard BRS, Medistar, Ljubljana, Slovenia). Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis. Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval (SDNN, milliseconds)and the root mean square of successive beat-to-beat differences in R-R interval duration (rMSSD milliseconds). For calculation of SDNN, the R-R intervals are visually inspected, and data considered as artifact is manually removed.
Change in Baroflex Sensitivity (BRS)
Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system at 1000 Hz, are analyzed using Nevrokard BRS software. Analysis is conducted on the first complete 5-minute epoch. Power spectral densities of systolic blood pressure (SBP) and R-R interval (RRI) oscillations are computed by 512 points Fast Fourier Transform (FFT) and integrated over specified frequency ranges (HF: 0.15-0.4 Hz). The square-root of the ratio of RRI's and SBP powers is computed to calculate HF alpha indices, which reflect BRS. The software scans the RRI and SBP records, identifies sequences, and calculates linear correlation between RRI and SBP for each sequence. The mean of all individual regression coefficients (slopes), a measure of sequence BRS, is then calculated for Sequence UP, DOWN and TOTAL (seq ALL).
Full Information
NCT ID
NCT01971567
First Posted
October 23, 2013
Last Updated
August 10, 2018
Sponsor
Wake Forest University Health Sciences
1. Study Identification
Unique Protocol Identification Number
NCT01971567
Brief Title
High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia
Official Title
High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia: A Randomized, Placebo-Controlled Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2018
Overall Recruitment Status
Completed
Study Start Date
October 2013 (Actual)
Primary Completion Date
December 12, 2016 (Actual)
Study Completion Date
February 6, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to determine whether the addition of High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) to usual care will improve insomnia symptoms based on changes in the Insomnia Severity Index at two months following completion of the intervention, compared to placebo plus usual care.
Detailed Description
Insomnia is the most prevalent sleep disorder and is associated with significant psychosocial and somatic pathology. Effective noninvasive interventions for insomnia are lacking. High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM), is a noninvasive, brain feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time. An open label, randomized, crossover pilot trial showed that HIRREM was safe and effective, with significant benefits for individuals with moderate to severe insomnia, based on differential change with symptoms of insomnia (Insomnia Severity Index, ISI). This study will extend those results in a larger cohort using a single blind, placebo controlled study design.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Insomnia
Keywords
Insomnia, Electroencephalic, Biofeedback, Neural oscillations, Auto calibration, Relaxation
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
107 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HIRREM
Arm Type
Active Comparator
Arm Description
High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, electroencephalic-based feedback technology to facilitate relaxation and auto-calibration of neural oscillations by using auditory tones to reflect brain frequencies in near real time.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Subjects in this arm will receive a sham-HIRREM placebo, for which the scalp sensors have no active recording capability, and for which the auditory tonal feedback is randomly generated rather than based on current brain frequencies and amplitudes.
Intervention Type
Device
Intervention Name(s)
HIRREM
Other Intervention Name(s)
High-resolution, relational, resonance-based, electroencephalic mirroring, Brainwave Optimization
Primary Outcome Measure Information:
Title
Change From Baseline in Insomnia Severity Index (ISI)
Description
The ISI is a 7 question, self-reported measure to evaluate symptoms of insomnia, with responses from 0-4 for each question, yielding scores ranging from 0-28. Lower scores represent better outcomes. The primary outcome will be change from enrollment to 8-10 weeks after completion of the intervention.
Time Frame
Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
Secondary Outcome Measure Information:
Title
Change From Baseline in Sleep Onset Latency and Wake After Sleep Onset
Description
This will be an online daily sleep diary to evaluate the amount and quality of sleep. This allows evaluation of the timing and trajectory of any improvements in sleep, including appreciation of the presence and duration of placebo effects. Measurements of sleep onset latency (SOL) and wake after sleep onset (WASO) were recorded in minutes.
Time Frame
Baseline and 8-10 weeks after completion of intervention
Title
Change in Total Sleep Time (TST)
Description
This will be an online daily sleep diary to evaluate the amount and quality of sleep. This allows evaluation of the timing and trajectory of any improvements in sleep, including appreciation of the presence and duration of placebo effects. Participants recorded the total sleep time (TST) they had each night. The outcome indicates the average increase (in hours) of the amount of sleep that each group reported.
Time Frame
Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
Title
Change in RestRefresh and SleepQual
Description
This will be an online daily sleep diary to evaluate the amount and quality of sleep. This allows evaluation of the timing and trajectory of any improvements in sleep, including appreciation of the presence and duration of placebo effects. Participants were asked to report a self-rating on how well they felt rested and refreshed (RestRefresh) and to rate the quality of sleep they had (SleepQual). Both questions were rated on a 0 to 4 scale and higher scores denotes better outcomes for each.
Time Frame
Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
Title
Change From Baseline in Beck Depression Inventory - II (BDI-II)
Description
Depression will be measured by the Beck Depression Inventory-II (BDI-II). The BDI-II is a 21-item questionnaire with response values of 0-3 for each item, yielding scores ranging from 0-63. Higher scores denotes worse outcomes.
Time Frame
Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
Title
Change From Baseline in Beck Anxiety Inventory (BAI)
Description
Anxiety will be measured by the Beck Anxiety Inventory (BAI). The BAI is a 21-item questionnaire with response values from 0-3 for each item, yielding scores ranging from 0-63. Higher scores denotes worse outcomes.
Time Frame
Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
Title
Change From Baseline in EQ-5D
Description
Health-related quality of life will be measured by the EQ-5D. The EQ-5D consists of 5 items assessing an individual's current health status (values from 0-2), yielding scores ranging from 0-10. Higher scores denotes worse outcomes.
Time Frame
Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
Title
Change in Heart Rate Variability (HRV)
Description
Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system (BIOPAC acquisition system and Acknowledge 4.2 software, Santa Barbara, CA), at 1000 Hz, are analyzed using Nevrokard BRS software (Nevrokard BRS, Medistar, Ljubljana, Slovenia). Analysis is conducted on the first complete 5-minute epoch that is considered to be acceptable for analysis. Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval (SDNN, milliseconds)and the root mean square of successive beat-to-beat differences in R-R interval duration (rMSSD milliseconds). For calculation of SDNN, the R-R intervals are visually inspected, and data considered as artifact is manually removed.
Time Frame
Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
Title
Change in Baroflex Sensitivity (BRS)
Description
Blood pressure and heart rate are acquired from 10 minute recordings of noninvasive finger arterial pressure measurements and ECG with participants lying quietly, supine. Systolic BP and beat to beat, RR intervals files generated via the data acquisition system at 1000 Hz, are analyzed using Nevrokard BRS software. Analysis is conducted on the first complete 5-minute epoch. Power spectral densities of systolic blood pressure (SBP) and R-R interval (RRI) oscillations are computed by 512 points Fast Fourier Transform (FFT) and integrated over specified frequency ranges (HF: 0.15-0.4 Hz). The square-root of the ratio of RRI's and SBP powers is computed to calculate HF alpha indices, which reflect BRS. The software scans the RRI and SBP records, identifies sequences, and calculates linear correlation between RRI and SBP for each sequence. The mean of all individual regression coefficients (slopes), a measure of sequence BRS, is then calculated for Sequence UP, DOWN and TOTAL (seq ALL).
Time Frame
8-10 weeks after completion of the intervention
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Moderate to severe clinical insomnia (Insomnia Severity Index score of 15 or higher)
Exclusion Criteria:
Unable, unwilling, or incompetent to provide informed consent
Physically unable to come to the study visits
Known obstructive sleep apnea
Diagnosed periodic limb movement disorder or known restless legs syndrome
Known seizure disorder
Known urinary problem (i.e. benign prostatic hypertrophy) which is the likely cause of the sleep disturbance
Severe hearing impairment
Known, or suspected diagnosis of post-traumatic stress disorder (PTSD)
Known, relevant traumatic brain injury (TBI)
Ongoing need for treatment with opiate, benzodiazepine, or anti-psychotic medications, anti-depressant medications such as SSRI, SNRI, or tricyclics, and sleep medications such as zolpidem or eszopiclone
Anticipated and ongoing use of recreational drugs or alcohol
Lack of internet or smart phone access
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles H. Tegeler, MD
Organizational Affiliation
Department of Neurology, Wake Forest School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurology, Wake Forest School of Medicine
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
23532171
Citation
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.
Results Reference
background
PubMed Identifier
23170244
Citation
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.
Results Reference
background
PubMed Identifier
32940419
Citation
Tegeler CL, Shaltout HA, Lee SW, Simpson SL, Gerdes L, Tegeler CH. High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) improves symptoms and autonomic function for insomnia: A randomized, placebo-controlled clinical trial. Brain Behav. 2020 Nov;10(11):e01826. doi: 10.1002/brb3.1826. Epub 2020 Sep 17.
Results Reference
derived
Learn more about this trial
High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia
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