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HIRREM Hot Flashes Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03512002
Recruitment Status : Recruiting
First Posted : April 30, 2018
Last Update Posted : May 21, 2020
Sponsor:
Information provided by (Responsible Party):
Wake Forest University Health Sciences

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.

Condition or disease Intervention/treatment Phase
Vasomotor Symptoms Hot Flashes Menopause Device: HIRREM Other: Continued Current Care Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention 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)
Primary Purpose: Supportive Care
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
Actual Study Start Date : June 1, 2018
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : June 2021

Arm Intervention/treatment
Active Comparator: 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.
Device: HIRREM
Technology
Other Names:
  • High-resolution, relational, resonance-based, electroencephalic mirroring
  • Brainwave Optimization

Other: Continued Current Care
Continue their current clinical care.

Continued Current Care
Participants will continue their current care.
Device: HIRREM
Technology
Other Names:
  • High-resolution, relational, resonance-based, electroencephalic mirroring
  • Brainwave Optimization

Other: Continued Current Care
Continue their current clinical care.




Primary Outcome Measures :
  1. Reduction in frequency and severity of hot flashes score based on diary data [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 weeks after V1 for CCC). ]
    Both groups will maintain 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 reduction in frequency and severity of hot flashes score from V1 to V2.


Secondary Outcome Measures :
  1. Change in Heart Rate Variability [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 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 (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.

  2. Change in Baroreflex Sensitivity [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 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 (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.

  3. Change in Insomnia Severity Index (ISI) [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 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.

  4. Change in Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 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.

  5. Change in Epworth Sleepiness Score (ESS) [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 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.

  6. Change in Center for Epidemiologic Studies Depression Scale (CES-D) [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 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.

  7. Change in Generalized Anxiety Disorder-7 (GAD-7) [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 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.

  8. Change in Perceived Stress Scale (PSS) [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 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.

  9. Change in Quality of Life Scale (QOLS) [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 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).

  10. Change in Drop Stick Reaction Time [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 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.

  11. Change in Grip Strength [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 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.

  12. Change in Hot Flash Related Daily Interference Scale (HFRDIS) [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 weeks after V1 for CCC). ]
    The HFRDIS is a 10 item measure to capture the daily impact of vasomotor symptoms in a variety of domains within the past week. These domains include work, social activities, leisure activities, sleep, mood, concentration, relation with others, sexuality, enjoyment of life, and overall quality of life. Items are scored from 0 (do not interfere) to 10 (completely interfere). A higher score indicates that the symptoms are interfering with daily life more.

  13. Change in Menopause Rating Scale (MRS) [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 weeks after V1 for CCC). ]
    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.


Other Outcome Measures:
  1. Change in Alcohol Intake Screening (Audit-C) [ Time Frame: Baseline, V2 (4-6 weeks after intervention completion for HCC, 10-12 weeks after V1 for CCC), and V3 (12-14 weeks following completion of the intervention for HCC, 18-20 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   40 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Participants must have an intact uterus and ovaries due to the nature of the study.
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03512002


Contacts
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Contact: Study Coordinator 336-716-9447 wfhirrem@wakehealth.edu

Locations
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United States, North Carolina
Department of Neurology, Wake Forest School of Medicine Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Study Coordinator    336-716-9447    wfhirrem@wakehealth.edu   
Principal Investigator: Charles H. Tegeler, MD         
Sponsors and Collaborators
Wake Forest University Health Sciences
Investigators
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Principal Investigator: Charles H. Tegeler, MD Wake Forest University Health Sciences
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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03512002    
Other Study ID Numbers: IRB00049252
First Posted: April 30, 2018    Key Record Dates
Last Update Posted: May 21, 2020
Last Verified: May 2020

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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
Keywords provided by Wake Forest University Health Sciences:
Neurotechnology
Autonomic Dysregulation
Hyperarousal
Brain Electrical Activity
HIRREM
Acoustic Stimulation
Perimenopausal
Postmenopausal
Hot Flashes
Night Sweats
Vasomotor Symptoms
Allostatis
Additional relevant MeSH terms:
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Hot Flashes