Trial Outcomes & Findings for HIRREM for Stage 1 Primary Hypertension (NCT NCT03479697)

NCT ID: NCT03479697

Last Updated: 2023-04-20

Results Overview

BP will be obtained in the left arm, with the participant sitting comfortably, and the left arm resting on a desk/table. Three samples will be obtained and the last two averaged to get the value that will be used as the reading. Primary outcome will be at V3 (4-6 weeks post final session).

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 5 participants
• Primary outcome timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).
• Results posted on: 2023-04-20

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	2	3
Overall Study COMPLETED	2	3
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

HIRREM for Stage 1 Primary Hypertension

Baseline characteristics by cohort

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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.	Total n=5 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	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Age, Continuous	34.00 years STANDARD_DEVIATION 1.41 • n=5 Participants	68.33 years STANDARD_DEVIATION 15.50 • n=7 Participants	54.60 years STANDARD_DEVIATION 21.78 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants	0 Participants n=7 Participants	2 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	2 Participants n=5 Participants	3 Participants n=7 Participants	5 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	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	2 Participants n=5 Participants	2 Participants n=7 Participants	4 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	2 participants n=5 Participants	3 participants n=7 Participants	5 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

BP will be obtained in the left arm, with the participant sitting comfortably, and the left arm resting on a desk/table. Three samples will be obtained and the last two averaged to get the value that will be used as the reading. Primary outcome will be at V3 (4-6 weeks post final session).

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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change From Baseline in Blood Pressure, as Measured by an Automated Oscillometric Blood Pressure Device. ∆_V1_V3 Diastolic	-6.00 mmHg Standard Deviation 4.24	-7.67 mmHg Standard Deviation 13.80
Change From Baseline in Blood Pressure, as Measured by an Automated Oscillometric Blood Pressure Device. ∆_V1_V3 Systolic	-3.00 mmHg Standard Deviation 8.49	-6.67 mmHg Standard Deviation 22.55

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval

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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Heart Rate Variability (SDNN)	17.55 ms Standard Deviation 16.48	9.47 ms Standard Deviation 3.83

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Baroreflex Sensitivity	0.35 ms/mmHg Standard Deviation 12.66	-4.97 ms/mmHg Standard Deviation 28.14

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

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=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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Insomnia Severity Index (ISI)	-3.00 score on a scale Standard Deviation 2.83	-2.67 score on a scale Standard Deviation 5.13

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

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=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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Pittsburgh Sleep Quality Index (PSQI)	0 score on a scale Standard Deviation 1.41	-1.33 score on a scale Standard Deviation 1.53

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

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=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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Epworth Sleepiness Score (ESS)	1.50 score on a scale Standard Deviation 2.12	-0.67 score on a scale Standard Deviation 2.08

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

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=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=3 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)	7.00 score on a scale Standard Deviation 1.41	1.33 score on a scale Standard Deviation 5.13

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

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=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=3 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)	4.50 score on a scale Standard Deviation 3.54	1.00 score on a scale Standard Deviation 1.00

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

The PCL-C measures the American Psychiatric Association's Diagnostic and statistical manual of mental disorders (DSM-IV) Criteria B, C, & D of PTSD symptoms based on traumatic life experience related to civilians. Seventeen items are rated on a Likert scale with a composite score range of 17 to 85. A score of 44 or higher correlates with probability of civilian-related PTSD.

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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in PTSD Checklist for Civilians (PCL-C)	6.00 score on a scale Standard Deviation 9.90	-4.00 score on a scale Standard Deviation 5.20

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

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=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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Perceived Stress Scale (PSS)	5.50 score on a scale Standard Deviation 4.95	-3.33 score on a scale Standard Deviation 1.15

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

This is a four item questionnaire asking about physical activity in the last 7 days. Scores are calculated and categorized as low, moderate, or high. A higher score denotes more physical activity. For results, categories could not be presented so they were coded as: 1=low, 2=moderate, and 3=high.

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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in International Physical Activity Questionnaire (IPAQ-SF)	0.00 score on a scale Standard Deviation 2.83	0.00 score on a scale Standard Deviation 0.00

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

This is a four item questionnaire asking about the participants level of satisfaction with their physical activity. Responses range from 0-6 for each question, yielding scores ranging from 0-24. Higher scores denote a higher level of satisfaction.

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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in HIRREM Physical Activity Satisfaction Questions	3.50 score on a scale Standard Deviation 2.12	2.00 score on a scale Standard Deviation 3.46

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

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=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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Quality of Life Scale (QOLS)	-4.00 score on a scale Standard Deviation 5.66	4.33 score on a scale Standard Deviation 7.23

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

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=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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Drop Stick Reaction Time	-0.06 cm Standard Deviation 0.27	-0.96 cm Standard Deviation 3.01

SECONDARY outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

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=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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Grip Strength ∆_V1_V3 Right Hand	16.17 lbs Standard Deviation 18.15	0.00 lbs Standard Deviation 6.01
Change in Grip Strength ∆_V1_V3 Left Hand	-2.33 lbs Standard Deviation 3.77	2.44 lbs Standard Deviation 5.54

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC).

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=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=3 Participants Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care.
Change in Alcohol Intake Screening (Audit-C)	-1.50 score on a scale Standard Deviation 0.71	0.00 score on a scale Standard Deviation 0.00

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