Trial Outcomes & Findings for HIRREM Hot Flashes Study (NCT NCT03512002)

NCT ID: NCT03512002

Last Updated: 2023-05-23

Results Overview

Both groups maintained a hot flash diary for 7-14 days, after which the intervention will begin for the HCC group. Post-intervention data collections will include an intermediate post-intervention visit (V2, primary outcome, 4-6 weeks after intervention completion for HCC, and 10-12 weeks after V1 for CCC), and a final follow up visit (V3, 12-14 weeks following completion of the intervention for HCC, and 18-20 weeks after V1 for CCC). Both groups will maintain a hot flash diary for 1-2 weeks prior to the V2 and V3 visits. The primary outcome will be change in hot flashes score from V1 to V2. The hot flash severity score for each day was calculated as the sum of the number of hot flashes within each severity category, multiplied by the severity score for that category, with the resulting sum divided by the total number of hot flashes. Scale ranges from 0 (no hot flashes) to an open ended upper number (no max since participant dependent). A higher number suggest worse hot flashes.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 8 participants
• Primary outcome timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).
• Results posted on: 2023-05-23

Participant Flow

Participant milestones

Measure	HIRREM High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Overall Study STARTED	3	5
Overall Study COMPLETED	3	5
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

HIRREM Hot Flashes Study

Baseline characteristics by cohort

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Total n=8 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	53.00 years STANDARD_DEVIATION 3.46 • n=5 Participants	54.80 years STANDARD_DEVIATION 5.12 • n=7 Participants	54.13 years STANDARD_DEVIATION 4.39 • n=5 Participants
Sex: Female, Male Female	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	1 Participants n=5 Participants	5 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants	5 participants n=7 Participants	8 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

Both groups maintained a hot flash diary for 7-14 days, after which the intervention will begin for the HCC group. Post-intervention data collections will include an intermediate post-intervention visit (V2, primary outcome, 4-6 weeks after intervention completion for HCC, and 10-12 weeks after V1 for CCC), and a final follow up visit (V3, 12-14 weeks following completion of the intervention for HCC, and 18-20 weeks after V1 for CCC). Both groups will maintain a hot flash diary for 1-2 weeks prior to the V2 and V3 visits. The primary outcome will be change in hot flashes score from V1 to V2. The hot flash severity score for each day was calculated as the sum of the number of hot flashes within each severity category, multiplied by the severity score for that category, with the resulting sum divided by the total number of hot flashes. Scale ranges from 0 (no hot flashes) to an open ended upper number (no max since participant dependent). A higher number suggest worse hot flashes.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Reduction in Hot Flash Severity Score Based on Diary Data	-0.39 score on a scale Standard Deviation 0.54	-0.38 score on a scale Standard Deviation 0.42

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

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). For calculation of SDNN, the R-R intervals are visually inspected, and data considered as artifact is manually removed.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Heart Rate Variability	-0.20 ms Standard Deviation 7.88	-5.42 ms Standard Deviation 8.00

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

Population: For one participant in HCC at V1, the Sequence ALL data was bad so the analysis could not be completed.

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. A measure of sequence BRS is then calculated as Sequence ALL.

Outcome measures

Measure	HIRREM n=2 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Baroreflex Sensitivity	1.60 ms/mmHg Standard Deviation 0.57	-1.54 ms/mmHg Standard Deviation 5.07

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

The severity of insomnia symptoms is measured using the ISI with each data collection visit. The ISI is a 7 question measure, with responses from 0-4 for each question, yielding scores ranging from 0-28. Higher scores indicate the strength of the insomnia severity.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Insomnia Severity Index (ISI)	-11.33 score on a scale Standard Deviation 3.79	-3.80 score on a scale Standard Deviation 4.21

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

The PSQI is a 19 item inventory that assesses sleep quality over a 1-month time interval. Items are weighted on a 0-3 interval scale. A global PSQI score is calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Pittsburgh Sleep Quality Index (PSQI)	-2.67 score on a scale Standard Deviation 2.31	-0.40 score on a scale Standard Deviation 3.29

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

The ESS measures a person's general level of daytime sleepiness, or their average sleep propensity in daily life. The simple questionnaire is based on retrospective reports of the likelihood of dozing off or falling asleep in a variety of different situations. Rated on a 4-point scale (0-3), it evaluates their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. Lower scores denote a lower level of daytime sleepiness.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Epworth Sleepiness Score (ESS)	-6.00 score on a scale Standard Deviation 1.00	-0.40 score on a scale Standard Deviation 2.61

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

The CES-D is a 20-item survey assessing affective depressive symptomatology to screen for risk of depression. Scores range from 0-60, with a score of 16 commonly used as a clinically relevant cut-off. Higher scores indicate the presence of more symptomatology.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Center for Epidemiologic Studies Depression Scale (CES-D)	-9.33 score on a scale Standard Deviation 5.03	2.80 score on a scale Standard Deviation 7.73

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

The GAD-7 is a seven item screening tool for anxiety that is widely used in primary care. Scores range from 0-21. A lower score denotes a lower level of anxiety.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Generalized Anxiety Disorder-7 (GAD-7)	-2.67 score on a scale Standard Deviation 2.08	0.20 score on a scale Standard Deviation 2.59

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

The PSS is a ten-item psychological instrument for measuring the perception of stress. It is a measure of the degree to which situations in one's life are appraised as stressful. Scores range from 0-40. A lower score denotes a lower level of perceived stress.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Perceived Stress Scale (PSS)	-1.67 score on a scale Standard Deviation 2.52	-0.20 score on a scale Standard Deviation 7.19

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

The QOLS is a 16-item scale that was modified from a 15-item scale used in chronic disease patients. Topics include different components of daily life such as relationships, community engagement, personal fulfillment, and recreation. Each item is scaled from 1 to 7 and a sum score is calculated to represent higher levels of satisfaction in life (range is 16-112).

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Quality of Life Scale (QOLS)	8.33 score on a scale Standard Deviation 5.03	-1.40 score on a scale Standard Deviation 6.35

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

Reaction testing will be evaluated by a drop-stick, clinical reaction time apparatus. The apparatus is placed between the thumb and index finger of the subject and released at a random time during a countdown. The subject catches the apparatus and the distance fallen (cm) is converted to reaction. Following two practice trials, participants perform eight trials, and a mean distance value is calculated. This is repeated with a second set of 8 trials later during the enrollment visit, and the mean distance value from the second trial will be used as the baseline value. Use of the average distance from the second set of trials will be used as the baseline value so as to avoid the impact of learning effect for this test. Only one set of trials will be used for comparison at follow up data collections. A lower average indicates a faster reaction time.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Drop Stick Reaction Time	3.88 cm Standard Deviation 6.17	3.85 cm Standard Deviation 5.59

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

Grip strength will be evaluated using a hydraulic hand dynamometer (Baseline Hydraulic Hand Dynamometer). Participants will squeeze the dynamometer three times in each hand. The scores from each hand will be averaged separately. A higher score indicates stronger grip strength.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Grip Strength ∆_V1_V2 Left Hand	3.56 lbs Standard Deviation 3.67	2.00 lbs Standard Deviation 1.20
Change in Grip Strength ∆_V1_V2 Right Hand	6.00 lbs Standard Deviation 6.12	3.20 lbs Standard Deviation 4.23

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

The HFRDIS is a 10 item measure to capture the daily impact of vasomotor symptoms in a variety of domains within the past week. Items are scored from 0 (do not interfere) to 10 (completely interfere). Total scores range from 0-100. A higher score indicates that the symptoms are interfering with daily life more.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Hot Flash Related Daily Interference Scale (HFRDIS)	-34.67 score on a scale Standard Deviation 38.68	-0.20 score on a scale Standard Deviation 23.66

SECONDARY outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

The MRS is a survey that generates a score between 0 and 44 based on the individual's symptom severity rankings. There are 11 symptoms listed related to perimenopause that are each assigned a score of 0 to 4 by the individual. A score of 0 indicates none, 1 is mild, 2 is moderate, 3 is severe, and 4 is very severe. After completion, the individual's score is tallied to create an overall score. Scores from 0-4 are considered zero to little, scores from 5-8 are considered mild, scores from 9-16 are moderate, and scores 17 or greater are considered severe.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Menopause Rating Scale (MRS)	-8.00 score on a scale Standard Deviation 2.65	0.00 score on a scale Standard Deviation 3.39

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to V2 (4-6 weeks following completion of the intervention).

The AUDIT-C is a short, 3-item alcohol screening for hazardous drinkers or active alcohol use disorders. This measure consists of 3 questions to assess an individual's alcohol use. Each question has five possible answers ranging from of 0-4 with a total scoring scale of 0-12. A total score of three or more in women and a score of four or more in men is suggestive of hazardous drinking or active alcohol use disorders.

Outcome measures

Measure	HIRREM n=3 Participants High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM) is a novel, noninvasive, closed-loop, brainwave mirroring, acoustic stimulation neurotechnology to support relaxation and auto-calibration of neural oscillations, using auditory tones to reflect brain frequencies in near real time. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Continued Current Care n=5 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Alcohol Intake Screening (Audit-C)	-0.33 score on a scale Standard Deviation 0.58	0.00 score on a scale Standard Deviation 1.22

Adverse Events

HIRREM

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Continued Current Care

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Charles Tegeler, MD

Atrium Wake Forest Baptist Health School of Medicine

Phone: 336-716-9447

Email: BBRP@wakehealth.edu

Results disclosure agreements

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