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Cereset Research Exploratory 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: NCT03777267
Recruitment Status : Recruiting
First Posted : December 17, 2018
Last Update Posted : January 5, 2021
Sponsor:
Collaborator:
The Susanne Marcus Collins Foundation, Inc
Information provided by (Responsible Party):
Wake Forest University Health Sciences

Brief Summary:
The purpose of this study is to evaluate the use of Cereset Research to improve autonomic function in participants with symptoms of stress, anxiety, or insomnia.

Condition or disease Intervention/treatment Phase
Neurological Diseases or Conditions Cardiovascular Conditions After Birth Psychophysiologic Disorders Device: Active CR Not Applicable

Detailed Description:

The primary objective of this open label exploratory study is to evaluate the effect of CR to improve autonomic cardiovascular regulation in participants with symptoms of stress, anxiety, or insomnia.

The secondary objective is to evaluate the effect of CR on a variety of self-reported symptom inventories.

Tertiary objectives are to explore the impact of selected medications on outcomes associated with use of CR, the effect size in subgroups of participants who also report specific co-morbid symptoms or conditions of interest, and any unexpected challenges or barriers for working with the same. The latter includes those with TBI, PTSD, hypertension, hot flashes, chronic pain, or prior stroke.

Methods: This will be a single site, open label, pilot clinical trial, enrolling people aged 11 or older, who have self-reported symptoms of stress, anxiety, or insomnia, and meet a threshold score on self-reported inventories. Up to 150 participants will be enrolled. Participants will receive between 6 and 12 sessions of audible tones echoing current brainwave activity (CR). Participants will continue their other current care throughout the study. There will be pre- and post-intervention data collection of physiological outcomes (BP, HR, and measures of autonomic cardiovascular regulation assessed by heart rate variability and baroreflex sensitivity), which will alse serve as the primary outcome. Secondary outcomes to be collected include symptom inventories for insomnia (Insomnia Severity Index, ISI; Pittsburgh Sleep Quality Index, PSQI), depression (Center for Epidemiological Studies- Depression Scale, CES-D), anxiety (Generalized Anxiety Disorder-7, GAD-7), stress (Perceived Stress Scale, PSS), traumatic stress (PTSD Checklist for civilians, PCL-C, or military, PCL-M), , and overall quality of life (QOLS). Other secondary outcome inventories will be collected for physical activity (International Physical Activity Questionnaire, IPAQ-SF), and physical activity satisfaction questions, as well. Participants who also self-report having specific co-morbid symptoms or conditions of interest may complete additional condition-specific outcome measures. All measures will be collected at an enrollment visit (V1), and the intervention will begin 0-14 days thereafter. Mean contrasts will be used to compare the changes in measures of autonomic cardiovascular regulation from V1 to V3, the primary outcome, as well as for secondary outcomes. Linear mixed models, which can accommodate within-subject correlations due to repeated assessments over time, will be used to generate point estimates for effect size along with 95% confidence intervals.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This will be a single site, open label, pilot clinical trial, enrolling people aged 11 or older, who have self-reported symptoms of stress, anxiety, or insomnia, and meet a threshold score on self-reported inventories. Up to 100 participants will be enrolled so as to gather pilot data that will help inform regarding effect size, and dosing to support future cohort-specific randomized trials. Participants will receive between 6 and 12 intervention sessions of Cereset Research consisting of audible tones echoing current brainwave activity.
Masking: None (Open Label)
Primary Purpose: Supportive Care
Official Title: Cereset Research Exploratory Study
Actual Study Start Date : April 12, 2019
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2022

Arm Intervention/treatment
Experimental: Experimental: Active CR
For this single arm, open label, exploratory trial this will be the intervention arm using active CR.
Device: Active CR
The upgraded platform for medical research using the HIRREM technology has been rebranded as Cereset Research® (CR). This system uses the same core technology and algorithms to echo brainwaves in real-time using audible tones, as with HIRREM. The CR system also includes 64-bit processing architecture for faster feedback, the use of 4 sensors, and the use of standard protocols (with flexibility regarding the length and sequencing of the standard protocols), all done with eyes closed. Four sensors are applied to the scalp at a time. However, only two sensors are actively echoing feedback. The software automatically switches from one sensor pair to the other when needed. This reduces the number of sensor placement changes needed, resulting in shorter session time and fewer interruptions.




Primary Outcome Measures :
  1. Change in Heart Rate Variability [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    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. 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.

  2. Change in Baroreflex Sensitivity [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    BRS calculated by this method is based on quantification of sequences of at least three beats (n) in which SBP consecutively increases (UP sequence) or decreases (DOWN sequence), which are accompanied by changes in the same direction of the RRI of subsequent beats (n+1). The software scans the RRI and SBP records, identifies sequences, and calculates linear correlation between RRI and SBP for each sequence. The mean of all individual regression coefficients (slopes), a measure of sequence BRS, is calculated for Sequence UP, DOWN and ALL (ms/mmHg). 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).

  3. Change in Blood Pressure [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    BP measurements will be obtained using an automate oscillometric blood pressure device. Three samples will be obtained and the last two averaged to get the value that will be used as the reading for that visit.

  4. Change in Blood Pressure Variability [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    Systolic BP and beat to beat, RR intervals (RRI) files generated via the data acquisition system (BIOPAC acquisition system and software, Santa Barbara, CA) at 1000 Hz are analyzed using Nevrokard SA-BRS software (by Nevrokard Kiauta, d.o.o., Izola, Slovenia) for measures BPV.Frequency Method. Power spectral densities of SBP and RRI oscillations are computed by 512 points Fast Fourier Transform (FFT) and integrated over specified frequency ranges (LF: 0.04-0.15 Hz; HF: 0.15-0.4 Hz).


Secondary Outcome Measures :
  1. Change in Insomnia Severity Index (ISI) [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    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.

  2. Change in Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    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.

  3. Change in Center for Epidemiologic Studies Depression Scale (CES-D) [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    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.

  4. Change in Generalized Anxiety Disorder-7 (GAD-7) [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    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.

  5. Change in Perceived Stress Scale (PSS) [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    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.

  6. Change in Quality of Life Scale (QOLS) [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    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).

  7. Change in PTSD Checklist for Civilians (PCL-C) [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    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.

  8. Change in International Physical Activity Questionnaire (IPAQ-SF) [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    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.

  9. Change in HIRREM Physical Activity Satisfaction Questions [ Time Frame: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2) ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   11 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Subjects must have the ability to comply with basic instructions and be able to sit still comfortably with the sensor leads attached
  • Subjects experiencing symptoms of stress, anxiety, or insomnia, who meet threshold scores on one or more self-reported inventories for the same. This includes the Insomnia Severity Index (ISI, ≥ 8), the Perceived Stress Index (PSS, ≥ 14), or the Generalized Anxiety Disorder 7-item (GAD-7, ≥ 5) scale.

Exclusion Criteria:

  • Unable, unwilling, or incompetent to provide informed consent/assent.
  • Physically unable to come to the study visits, or to sit comfortably in a chair for up to 1.5 hours.
  • Severe hearing impairment (because the subject will be using ear buds during CR).
  • Anticipated and ongoing use of alcohol or recreational drugs.
  • Weight is over the chair limit (285 pounds).
  • Currently in another active intervention research study.
  • Prior use of HIRREM, Brainwave Optimization, Cereset, or a wearable configuration of the same (B2, or B2v2).
  • Prior use of electroconvulsive therapy (ECT).
  • Prior use of transcranial magnetic stimulation (TMS), transcranial direct current stimulation (TDCS), alpha stimulation, neurofeedback, biofeedback, or deep brain stimulation (DBS) within one month before enrollment.
  • Known seizure disorder.

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): NCT03777267


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, 27104
Contact: Study Coordinator    336-716-9447    wfhirrem@wakehealth.edu   
Principal Investigator: Charles Tegeler, MD         
Sponsors and Collaborators
Wake Forest University Health Sciences
The Susanne Marcus Collins Foundation, Inc
Investigators
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Principal Investigator: Charles Tegeler, MD Wake Forest University Health Sciences
Publications:
Tegeler CL, Howard LJ, Schmidt KD, Cook JF, Kumar S, Simpson SL, Lee SW, Gerdes L, Tegeler CH. 0389 USE OF A CLOSED-LOOP ACOUSTIC STIMULATION NEUROTECHNOLOGY IMPROVES SYMPTOMS OF MODERATE TO SEVERE INSOMNIA: RESULTS OF A PLACEBO-CONTROLLED TRIAL. Sleep. 2017;40:A145-A.
Shaltout HA, Tegeler CL, Lee SW, Tegeler CH. 0363 IN SUBJECTS WITH INSOMNIA, USE OF A CLOSED-LOOP ACOUSTIC STIMULATION NEUROTECHNOLOGY IMPROVES HEART RATE VARIABILITY AND BAROREFLEX SENSITIVITY: RESULTS OF A PLACEBO-CONTROLLED CLINICAL TRIAL. Sleep. 2017;40:A135-A
Kaplan NM RB. Technique of blood pressure measurement in the diagnosis of hypertension. UpToDate. Barkris GL, Sheridan AM, eds. Waltham, MA; 2010.
Radloff LS. The CES-D Scale: A Self-Report Depression Scale for Research in the General Population. Applied Psychological Measurement. 1977;1:385-401.
FW W, BT L, DS H, JA H, TM K. The PTSD Checklist (PCL): Reliability, validity, and diagnostic utility. 9th Annual Meeting of the International Society for Traumatic Stress Studies. San Antonio, TX.

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Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03777267    
Other Study ID Numbers: IRB00055280
First Posted: December 17, 2018    Key Record Dates
Last Update Posted: January 5, 2021
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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.: Yes
Keywords provided by Wake Forest University Health Sciences:
Stress
Neurotechnology
Autonomic Dysregulation
Hyperarousal
Brain electrical activity
Allostasis
HIRREM
Cereset Research
Insomnia
Anxiety
Additional relevant MeSH terms:
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Nervous System Diseases
Disease
Psychophysiologic Disorders
Pathologic Processes
Neurologic Manifestations