Back to resultsHIRREM Hot Flashes Study
Primary Purpose
Vasomotor Symptoms, Hot Flashes, Menopause
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
HIRREM
Continued Current Care
Sponsored by
About this trial
This is an interventional supportive care trial for Vasomotor Symptoms focused on measuring Neurotechnology, Autonomic Dysregulation, Hyperarousal, Brain Electrical Activity, HIRREM, Acoustic Stimulation, Perimenopausal, Postmenopausal, Hot Flashes, Night Sweats, Vasomotor Symptoms, Allostatis
Eligibility Criteria
Inclusion Criteria:
- Women, age 40 and above
- Intact uterus and ovaries
- Have at least 5 hot flashes per day (with at least one being categorized as moderate to severe, in a stable pattern for one month).
Exclusion Criteria:
- Less than 5 hot flashes per day
- Does not experience at least 1 moderate to severe hot flash per day
- 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
- Known seizure disorder
- Known or potential pregnancy (females with last menstrual period less than one year from enrollment will be tested for pregnancy prior to randomization)
- 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
- Use of pharmaceuticals for treatment of vasomotor symptoms or any type of hormone replacement therapy
- Use of supplements for improvement of vasomotor symptoms including but not limited to black cohosh, soy isoflavone extract, and red clover leaf extract
- Menopausal symptoms resulting from, or associated with surgery, chemotherapy, radiation, or use of other chemicals or medications
- Anticipated and ongoing use of recreational drugs, alcohol, or energy drinks
- Ongoing need for treatment with thyroid medications
- Weight is over the chair limit (285 pounds)
- Are enrolled in another research study that includes an active intervention
- Have previously received brainwave optimization (BWO), used a B2 or a B2v2 wearable device, or previously participated in a HIRREM research study
Sites / Locations
- Department of Neurology, Wake Forest School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Other
Arm Label
HIRREM
Continued Current Care
Arm Description
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.
Participants will continue their current care.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
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.
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).
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.
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.
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.
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.
Full Information
NCT ID
NCT03512002
First Posted
April 18, 2018
Last Updated
April 27, 2023
Sponsor
Wake Forest University Health Sciences
1. Study Identification
Unique Protocol Identification Number
NCT03512002
Brief Title
HIRREM Hot Flashes Study
Official Title
High-Resolution, Relational, Resonance-Based, Electroencephalic Mirroring (HIRREM) for Vasomotor Symptoms (Hot Flashes) in Perimenopausal and Postmenopausal Women: A Randomized, Controlled Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Completed
Study Start Date
June 1, 2018 (Actual)
Primary Completion Date
May 27, 2020 (Actual)
Study Completion Date
May 27, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Wake Forest University Health Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vasomotor Symptoms, Hot Flashes, Menopause
Keywords
Neurotechnology, Autonomic Dysregulation, Hyperarousal, Brain Electrical Activity, HIRREM, Acoustic Stimulation, Perimenopausal, Postmenopausal, Hot Flashes, Night Sweats, Vasomotor Symptoms, Allostatis
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
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)
Allocation
Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
HIRREM
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Continued Current Care
Arm Type
Other
Arm Description
Participants will continue their current care.
Intervention Type
Device
Intervention Name(s)
HIRREM
Other Intervention Name(s)
High-resolution, relational, resonance-based, electroencephalic mirroring, Brainwave Optimization
Intervention Description
Technology
Intervention Type
Other
Intervention Name(s)
Continued Current Care
Intervention Description
Continue their current clinical care.
Primary Outcome Measure Information:
Title
Reduction in Hot Flash Severity Score Based on Diary Data
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Secondary Outcome Measure Information:
Title
Change in Heart Rate Variability
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Title
Change in Baroreflex Sensitivity
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Title
Change in Insomnia Severity Index (ISI)
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Title
Change in Pittsburgh Sleep Quality Index (PSQI)
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Title
Change in Epworth Sleepiness Score (ESS)
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Title
Change in Center for Epidemiologic Studies Depression Scale (CES-D)
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Title
Change in Generalized Anxiety Disorder-7 (GAD-7)
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Title
Change in Perceived Stress Scale (PSS)
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Title
Change in Quality of Life Scale (QOLS)
Description
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).
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Title
Change in Drop Stick Reaction Time
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Title
Change in Grip Strength
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Title
Change in Hot Flash Related Daily Interference Scale (HFRDIS)
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Title
Change in Menopause Rating Scale (MRS)
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
Other Pre-specified Outcome Measures:
Title
Change in Alcohol Intake Screening (Audit-C)
Description
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.
Time Frame
Baseline to V2 (4-6 weeks following completion of the intervention).
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
Participants must have an intact uterus and ovaries due to the nature of the study.
Minimum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Women, age 40 and above
Intact uterus and ovaries
Have at least 5 hot flashes per day (with at least one being categorized as moderate to severe, in a stable pattern for one month).
Exclusion Criteria:
Less than 5 hot flashes per day
Does not experience at least 1 moderate to severe hot flash per day
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
Known seizure disorder
Known or potential pregnancy (females with last menstrual period less than one year from enrollment will be tested for pregnancy prior to randomization)
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
Use of pharmaceuticals for treatment of vasomotor symptoms or any type of hormone replacement therapy
Use of supplements for improvement of vasomotor symptoms including but not limited to black cohosh, soy isoflavone extract, and red clover leaf extract
Menopausal symptoms resulting from, or associated with surgery, chemotherapy, radiation, or use of other chemicals or medications
Anticipated and ongoing use of recreational drugs, alcohol, or energy drinks
Ongoing need for treatment with thyroid medications
Weight is over the chair limit (285 pounds)
Are enrolled in another research study that includes an active intervention
Have previously received brainwave optimization (BWO), used a B2 or a B2v2 wearable device, or previously participated in a HIRREM research study
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Charles H. Tegeler, MD
Organizational Affiliation
Wake Forest University Health Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Neurology, Wake Forest School of Medicine
City
Winston-Salem
State/Province
North Carolina
ZIP/Postal Code
27157
Country
United States
12. IPD Sharing Statement
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HIRREM Hot Flashes Study
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