High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia

Study Overview
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Brief Summary
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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
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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.

Official Title
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High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia: A Randomized, Placebo-Controlled Clinical Trial

Conditions
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Insomnia

Intervention / Treatment
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* Device: HIRREM


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HIRREM<br>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. | Device: HIRREM<br> <br> * Other names: Brainwave Optimization;|
| Placebo Comparator: Placebo<br>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. | Device: HIRREM<br> <br> * Other names: Brainwave Optimization;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Baseline and 8-10 weeks after completion of intervention | 
| 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. | Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention | 
| 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. | Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention | 
| 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. | Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention | 
| 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. | Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention | 
| 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. | Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention | 
| 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. | Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention | 
| 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). | 8-10 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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Insomnia, Electroencephalic, Biofeedback, Neural oscillations, Auto calibration, Relaxation