- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01971567
High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia
August 10, 2018 updated by: Wake Forest University Health Sciences
High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia: A Randomized, Placebo-Controlled Clinical Trial
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.
Study Overview
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.
Study Type
Interventional
Enrollment (Actual)
107
Phase
- Not Applicable
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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North Carolina
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Winston-Salem, North Carolina, United States, 27157
- Department of Neurology, Wake Forest School of Medicine
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: HIRREM
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.
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Other Names:
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Placebo Comparator: Placebo
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.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Insomnia Severity Index (ISI)
Time Frame: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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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.
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Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change From Baseline in Sleep Onset Latency and Wake After Sleep Onset
Time Frame: Baseline and 8-10 weeks after completion of intervention
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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.
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Baseline and 8-10 weeks after completion of intervention
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Change in Total Sleep Time (TST)
Time Frame: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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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.
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Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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Change in RestRefresh and SleepQual
Time Frame: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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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.
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Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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Change From Baseline in Beck Depression Inventory - II (BDI-II)
Time Frame: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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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.
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Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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Change From Baseline in Beck Anxiety Inventory (BAI)
Time Frame: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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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.
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Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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Change From Baseline in EQ-5D
Time Frame: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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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.
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Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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Change in Heart Rate Variability (HRV)
Time Frame: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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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.
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Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
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Change in Baroflex Sensitivity (BRS)
Time Frame: 8-10 weeks after completion of the intervention
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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).
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8-10 weeks after completion of the intervention
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Investigators
- Principal Investigator: Charles H. Tegeler, MD, Department of Neurology, Wake Forest School of Medicine
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
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 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
October 1, 2013
Primary Completion (Actual)
December 12, 2016
Study Completion (Actual)
February 6, 2017
Study Registration Dates
First Submitted
October 23, 2013
First Submitted That Met QC Criteria
October 23, 2013
First Posted (Estimate)
October 29, 2013
Study Record Updates
Last Update Posted (Actual)
September 10, 2018
Last Update Submitted That Met QC Criteria
August 10, 2018
Last Verified
August 1, 2018
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IRB00024763
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
No
Studies a U.S. FDA-regulated device product
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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