Trial Outcomes & Findings for High-resolution, Relational, Resonance-based, Electroencephalic Mirroring (HIRREM) to Relieve Insomnia (NCT NCT01971567)

NCT ID: NCT01971567

Last Updated: 2018-09-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

107 participants

Primary outcome timeframe

Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

Results posted on

2018-09-10

Participant Flow

Participant milestones

Participant milestones
Measure
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. HIRREM
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. HIRREM
Overall Study
STARTED
56
51
Overall Study
COMPLETED
52
49
Overall Study
NOT COMPLETED
4
2

Reasons for withdrawal

Reasons for withdrawal
Measure
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. HIRREM
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. HIRREM
Overall Study
Withdrawal by Subject
3
2
Overall Study
Lost to Follow-up
1
0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
HIRREM
n=56 Participants
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. HIRREM
Placebo
n=51 Participants
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. HIRREM
Total
n=107 Participants
Total of all reporting groups
Age, Continuous
52.4 years
STANDARD_DEVIATION 15.1 • n=5 Participants
54.7 years
STANDARD_DEVIATION 14.8 • n=7 Participants
53.5 years
STANDARD_DEVIATION 14.9 • n=5 Participants
Sex: Female, Male
Female
41 Participants
n=5 Participants
32 Participants
n=7 Participants
73 Participants
n=5 Participants
Sex: Female, Male
Male
15 Participants
n=5 Participants
19 Participants
n=7 Participants
34 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · White
46 Participants
n=5 Participants
43 Participants
n=7 Participants
89 Participants
n=5 Participants
Race/Ethnicity, Customized
Ethnicity · Other
10 Participants
n=5 Participants
8 Participants
n=7 Participants
18 Participants
n=5 Participants
Duration with Sleep Trouble
11.1 years
STANDARD_DEVIATION 12.1 • n=5 Participants
12.2 years
STANDARD_DEVIATION 11.3 • n=7 Participants
11.7 years
STANDARD_DEVIATION 11.7 • n=5 Participants

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure
HIRREM
n=56 Participants
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. HIRREM
Placebo
n=51 Participants
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. HIRREM
Change From Baseline in Insomnia Severity Index (ISI)
-6.98 units on a scale
Standard Error 0.74
-4.94 units on a scale
Standard Error 0.76

SECONDARY outcome

Timeframe: Baseline and 8-10 weeks after completion of intervention

Population: Data was not able to be collected for all participants.

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.

Outcome measures

Outcome measures
Measure
HIRREM
n=47 Participants
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. HIRREM
Placebo
n=39 Participants
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. HIRREM
Change From Baseline in Sleep Onset Latency and Wake After Sleep Onset
SOL
-1.00 minutes
Standard Error 0.18
-0.56 minutes
Standard Error 0.14
Change From Baseline in Sleep Onset Latency and Wake After Sleep Onset
WASO
-28.42 minutes
Standard Error 8.00
-22.64 minutes
Standard Error 4.73

SECONDARY outcome

Timeframe: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

Population: Data was not able to be collected for all participants.

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.

Outcome measures

Outcome measures
Measure
HIRREM
n=47 Participants
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. HIRREM
Placebo
n=39 Participants
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. HIRREM
Change in Total Sleep Time (TST)
1.15 hours
Standard Error 0.23
0.58 hours
Standard Error 0.17

SECONDARY outcome

Timeframe: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

Population: Data was not able to be collected for all participants.

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.

Outcome measures

Outcome measures
Measure
HIRREM
n=47 Participants
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. HIRREM
Placebo
n=39 Participants
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. HIRREM
Change in RestRefresh and SleepQual
RestRefresh
0.60 units on a scale
Standard Error 0.16
0.54 units on a scale
Standard Error 0.12
Change in RestRefresh and SleepQual
SleepQual
0.79 units on a scale
Standard Error 0.16
0.67 units on a scale
Standard Error 0.12

SECONDARY outcome

Timeframe: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

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.

Outcome measures

Outcome measures
Measure
HIRREM
n=52 Participants
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. HIRREM
Placebo
n=49 Participants
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. HIRREM
Change From Baseline in Beck Depression Inventory - II (BDI-II)
-3.76 units on a scale
Standard Error 0.59
-2.65 units on a scale
Standard Error 0.61

SECONDARY outcome

Timeframe: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

Population: Data not collected for one participant in the placebo group

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.

Outcome measures

Outcome measures
Measure
HIRREM
n=52 Participants
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. HIRREM
Placebo
n=48 Participants
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. HIRREM
Change From Baseline in Beck Anxiety Inventory (BAI)
-0.25 units on a scale
Standard Error 0.10
-0.25 units on a scale
Standard Error 0.10

SECONDARY outcome

Timeframe: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

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.

Outcome measures

Outcome measures
Measure
HIRREM
n=52 Participants
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. HIRREM
Placebo
n=49 Participants
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. HIRREM
Change From Baseline in EQ-5D
2.73 units on a scale
Standard Error 1.90
0.11 units on a scale
Standard Error 1.94

SECONDARY outcome

Timeframe: Collected from the enrollment visit through completion of the primary data collection visit, 8-10 weeks after completion of the intervention

Population: Other entries were excluded due to missing or dropped heartbeats and were excluded from the analysis for continuity

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.

Outcome measures

Outcome measures
Measure
HIRREM
n=52 Participants
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. HIRREM
Placebo
n=47 Participants
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. HIRREM
Change in Heart Rate Variability (HRV)
rMSSD
53.06 ms
Standard Error 5.34
26.86 ms
Standard Error 2.24
Change in Heart Rate Variability (HRV)
SDNN
57.28 ms
Standard Error 1.34
35.81 ms
Standard Error 1.77

SECONDARY outcome

Timeframe: 8-10 weeks after completion of the intervention

Population: Other entries were excluded due to missing or dropped heartbeats and were excluded from the analysis for continuity

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).

Outcome measures

Outcome measures
Measure
HIRREM
n=52 Participants
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. HIRREM
Placebo
n=47 Participants
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. HIRREM
Change in Baroflex Sensitivity (BRS)
HF Alpha
24.78 ms/mm Hg
Standard Error 2.17
16.26 ms/mm Hg
Standard Error 1.73
Change in Baroflex Sensitivity (BRS)
Seq ALL
20.36 ms/mm Hg
Standard Error 2.03
12.31 ms/mm Hg
Standard Error 1.09

Adverse Events

HIRREM

Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
HIRREM
n=56 participants at risk
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. HIRREM
Placebo
n=51 participants at risk
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. HIRREM
General disorders
Change in sleep
3.6%
2/56 • 16-18 weeks after completion of the intervention
3.9%
2/51 • 16-18 weeks after completion of the intervention
Social circumstances
Change in emotions or awareness of feelings
1.8%
1/56 • 16-18 weeks after completion of the intervention
3.9%
2/51 • 16-18 weeks after completion of the intervention
General disorders
Head fullness
5.4%
3/56 • 16-18 weeks after completion of the intervention
3.9%
2/51 • 16-18 weeks after completion of the intervention
Skin and subcutaneous tissue disorders
Skin irritation at scalp sensor site
0.00%
0/56 • 16-18 weeks after completion of the intervention
2.0%
1/51 • 16-18 weeks after completion of the intervention

Additional Information

Dr. Charles H. Tegeler

Wake Forest School of Medicine

Phone: +1 (336) 716-7651

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place