InsomniaNCT01971567
High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia
A study testing HIRREM in people with Insomnia, run by Wake Forest University Health Sciences at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Insomnia
- What is being tested?
- HIRREM
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 107 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2013to 6 Feb 2017
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Moderate to severe clinical insomnia (Insomnia Severity Index score of 15 or higher)
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Department of Neurology, Wake Forest School of Medicine
Winston-Salem, North Carolina, 27157
About this study
Official title: 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.
Read the 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.
- Conditions
- Insomnia
- Being tested
- HIRREM
- Keywords
- Insomnia, Electroencephalic, Biofeedback, Neural oscillations, Auto calibration, Relaxation
- Medical subject headings
- Sleep Initiation and Maintenance Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HIRREMDevice
Also called High-resolution, relational, resonance-based, electroencephalic mirroring, Brainwave Optimization
| Study group | Role | What they receive |
|---|---|---|
| HIRREM | Active comparator | 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. Receives: Device: HIRREM |
| Placebo | Placebo comparator | 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. Receives: Device: HIRREM |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention
Secondary outcomes (8)
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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 8-10 weeks after completion of the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Oct 2013 (estimated)
- Study startOct 2013
- Primary completion12 Dec 2016
- Study completion6 Feb 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for InsomniaStudies of the same condition, open and under way.
- More trials run by Wake Forest University Health SciencesThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 107 participants (actual)
Sponsor and investigators
- Lead sponsor
- Wake Forest University Health Sciences
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Charles H. Tegeler, MD, Principal investigator, Department of Neurology, Wake Forest School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01971567
- Sponsor's protocol ID
- IRB00024763
- Status last verified
- Aug 2018
- First submitted
- 23 Oct 2013
- Last updated
- 10 Sep 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
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.
PubMed 23532171Tegeler 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.
PubMed 23170244Tegeler 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.
PubMed 32940419
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia: A Randomized, Placebo-Controlled Clinical Trial
- ClinicalTrials.gov ID
- NCT01971567
- Acronym / sponsor ID
- IRB00024763
- Conditions
- Insomnia
- Keywords
- Insomnia, Electroencephalic, Biofeedback, Neural oscillations, Auto calibration, Relaxation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 107 participants (actual)
- Lead sponsor
- Wake Forest University Health SciencesUniversity, hospital or other
- Study start
- Oct 2013 (actual)
- Primary completion
- 12 Dec 2016 (actual)
- Study completion
- 6 Feb 2017 (actual)
- First posted
- 29 Oct 2013 (estimated)
- Results
- Posted 21 May 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| HIRREM | Active comparator | Device: HIRREMHigh-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. |
| Placebo | Placebo comparator | Device: HIRREMSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Moderate to severe clinical insomnia (Insomnia Severity Index score of 15 or higher)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HIRREMAlso: High-resolution, relational, resonance-based, electroencephalic mirroring, Brainwave Optimization | Device | HIRREM, Placebo |
Primary outcome
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
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.
8 secondary outcomes
Change From Baseline in Sleep Onset Latency and Wake After Sleep Onset
Time frame: Baseline and 8-10 weeks after completion of intervention
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
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
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
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
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
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
Change in Baroflex Sensitivity (BRS)
Time frame: 8-10 weeks after completion of the intervention
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 23532171Gerdes 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.
- Background: PubMed 23170244Tegeler 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.
- Derived from this study: PubMed 32940419Tegeler 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Charles H. Tegeler, MD principal investigator
Department of Neurology, Wake Forest School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing HIRREM in people with Insomnia, run by Wake Forest University Health Sciences at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 21 May 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01971567, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2018.