HIRREM for Stage 1 Primary Hypertension

Study Overview
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Brief Summary
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The purpose of this study is to determine that effects of an intervention called High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM), on Stage 1 Primary Hypertension (systolic BP 130-139, and/or diastolic BP 80-89).

Detailed Description
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The purpose of this research study is to determine the effects of a technique called High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM®), for hypertension. HIRREM uses scalp sensors to monitor brain electrical activity, and computer software algorithms translate selected brain frequencies into audible tones in real time. Those tones are reflected back to participants via ear buds in as little as four to eight milliseconds, providing the brain an opportunity for self-adjustment of its electrical pattern. This study will compare acoustic stimulation linked to brainwave activity (HIRREM, along with continued current care, HCC), with continued current clinical care alone (CCC). Both groups will continue their other current care throughout, including non-pharmacological, and lifestyle modification therapies.

Official Title
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High-Resolution, Relational, Resonance-Based, Electroencephalic Mirroring (HIRREM) for Stage 1 Primary Hypertension

Conditions
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Hypertension, Blood Pressure, Cardiovascular Diseases, Cardiovascular Risk Factor, Autonomic Nervous System Imbalance

Intervention / Treatment
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* Device: HIRREM
* Other: Continued Current Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults, age 18 and above Systolic BP ranging from 130-139mmHg and/or diastolic BP ranging from 80-89mmHg Exclusion Criteria: Unable, unwilling, or incompetent to provide informed consent Physically unable to come to the study visits, or to sit comfortably in a chair for up to two hours at a time Weight is over the chair limit (285 pounds) Known atherosclerotic cardiovascular disease Cardiovascular risk score of ≥ 10% (per http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/calculate/estimate/) Prior diagnosis of stage 2 hypertension Ongoing need for treatment of hypertension with medications Known seizure disorder Known or anticipated pregnancy Severe hearing impairment (because the subject will be using headphones during the interventions) Ongoing need for treatment with opiate, benzodiazepine, or anti-psychotic medications, anti-depressant medications such as SSRI, SNRI, or tricyclic, and sleep medications such as zolpidem or eszopiclone Anticipated and ongoing use of recreational drugs, alcohol, or energy drinks Ongoing need for treatment with thyroid medications Are enrolled in another research study that includes an active intervention Have previously received brainwave optimization (BWO), used a B2 or B2v2 wearable device, or previously participated in a HIRREM research study

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: This study will compare acoustic stimulation linked to brainwave activity (HIRREM, along with continued current care, HCC), with continued current clinical care alone (CCC). Both groups will continue their other current care throughout, including non-pharmacological, and lifestyle modification therapies. The participants in the CCC group will be offered the opportunity to crossover and receive a course of HCC.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: HIRREM<br>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. | Device: HIRREM<br>* Technology<br>* Other names: Brainwave Optimization;Other: Continued Current Care<br>* Continue their current clinical care.<br>|
| Other: Continued Current Care<br>Participants will continue their current care. | Device: HIRREM<br>* Technology<br>* Other names: Brainwave Optimization;Other: Continued Current Care<br>* Continue their current clinical care.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Blood Pressure, as Measured by an Automated Oscillometric Blood Pressure Device. | 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). | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Heart Rate Variability (SDNN) | Heart rate variability is measured in the time domain as standard deviation of beat-to-beat interval | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in Baroreflex Sensitivity | 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. | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in Insomnia Severity Index (ISI) | 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. | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in Pittsburgh Sleep Quality Index (PSQI) | 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. | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in Epworth Sleepiness Score (ESS) | 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. | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in Center for Epidemiologic Studies Depression Scale (CES-D) | 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. | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in Generalized Anxiety Disorder-7 (GAD-7) | 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. | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in PTSD Checklist for Civilians (PCL-C) | 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. | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in Perceived Stress Scale (PSS) | 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. | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in International Physical Activity Questionnaire (IPAQ-SF) | 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. | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in HIRREM Physical Activity Satisfaction Questions | 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. | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in Quality of Life Scale (QOLS) | 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). | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in Drop Stick Reaction Time | 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. | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 
| Change in Grip Strength | 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. | Baseline to V3 (4-6 weeks following completion of the intervention for HCC, 8-10 weeks after V1 for CCC). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HIRREM, Neurotechnology, Closed-Loop, Allostasis, Stress, Autonomic Dysregulation, Hyperarousal, Brain Electrical Activity, Acoustic Stimulation, Primary Hypertension, High Blood Pressure