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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 women in any stage of menopause, who are experiencing menopause-related hot flashes.
The purpose of this research study is to determine the effects of a technique called High-resolution, relational, resonance-based, electroencephalic mirroring (HIRREM®), for hot flashes. 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HIRREM | Active Comparator | 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. |
|
| Continued Current Care | Other | Participants will continue their current care. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| HIRREM | Device | Technology |
|
| Measure | Description | Time Frame |
|---|---|---|
| Reduction in Hot Flash Severity Score Based on Diary Data | 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. | Baseline to V2 (4-6 weeks following completion of the intervention). |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Heart Rate Variability | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Alcohol Intake Screening (Audit-C) | 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. |
Inclusion Criteria:
Exclusion Criteria:
Participants must have an intact uterus and ovaries due to the nature of the study.
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| Name | Affiliation | Role |
|---|---|---|
| Charles H. Tegeler, MD | Wake Forest University Health Sciences | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Department of Neurology, Wake Forest School of Medicine | Winston-Salem | North Carolina | 27157 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| FG001 | Continued Current Care | Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Reduction in Hot Flash Severity Score Based on Diary Data | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
Baseline to V3 (12-14 weeks following completion of the intervention for HCC, 18-20 weeks after V1 for CCC).
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
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Medication exclusions and required minimum number of hot flashes per day made it difficult to recruit. COVID hit and the office shut down.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Charles Tegeler, MD | Atrium Wake Forest Baptist Health School of Medicine | 336-716-9447 | BBRP@wakehealth.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Mar 23, 2018 | Mar 27, 2023 | Prot_SAP_001.pdf |
| ICF | No | No | Yes | Informed Consent Form | Feb 27, 2020 | Mar 17, 2023 | ICF_002.pdf |
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| ID | Term |
|---|---|
| D019584 | Hot Flashes |
| D054969 | Primary Dysautonomias |
| ID | Term |
|---|---|
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D001342 | Autonomic Nervous System Diseases |
| D009422 | Nervous System Diseases |
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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.
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| Continued Current Care | Other | Continue their current clinical care. |
|
| Baseline to V2 (4-6 weeks following completion of the intervention). |
| 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 V2 (4-6 weeks following completion of the intervention). |
| 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 V2 (4-6 weeks following completion of the intervention). |
| 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 V2 (4-6 weeks following completion of the intervention). |
| 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 V2 (4-6 weeks following completion of the intervention). |
| 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 V2 (4-6 weeks following completion of the intervention). |
| 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 V2 (4-6 weeks following completion of the intervention). |
| 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 V2 (4-6 weeks following completion of the intervention). |
| 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 V2 (4-6 weeks following completion of the intervention). |
| 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 V2 (4-6 weeks following completion of the intervention). |
| 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 V2 (4-6 weeks following completion of the intervention). |
| Change in Hot Flash Related Daily Interference Scale (HFRDIS) | 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. | Baseline to V2 (4-6 weeks following completion of the intervention). |
| Change in Menopause Rating Scale (MRS) | 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. | Baseline to V2 (4-6 weeks following completion of the intervention). |
| Baseline to V2 (4-6 weeks following completion of the intervention). |
| BG001 | Continued Current Care | Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG000 | 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. |
| OG001 | Continued Current Care | Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care. |
|
|
| Secondary | Change in Heart Rate Variability | 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. | Posted | Mean | Standard Deviation | ms | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Secondary | 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. | For one participant in HCC at V1, the Sequence ALL data was bad so the analysis could not be completed. | Posted | Mean | Standard Deviation | ms/mmHg | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Secondary | 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). | Posted | Mean | Standard Deviation | score on a scale | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | cm | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Secondary | 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. | Posted | Mean | Standard Deviation | lbs | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Secondary | Change in Hot Flash Related Daily Interference Scale (HFRDIS) | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Secondary | Change in Menopause Rating Scale (MRS) | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
|
|
| Other Pre-specified | Change in Alcohol Intake Screening (Audit-C) | 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. | Posted | Mean | Standard Deviation | score on a scale | Baseline to V2 (4-6 weeks following completion of the intervention). |
|
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|
| 0 |
| 3 |
| 0 |
| 3 |
| 0 |
| 3 |
| EG001 | Continued Current Care | Participants will continue their current care. HIRREM: Technology Continued Current Care: Continue their current clinical care. | 0 | 5 | 0 | 5 | 0 | 5 |
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