AzTrials
AzTrials

Neurological Diseases or ConditionsNCT03777267

Cereset Research Exploratory Study

A study testing Active CR in people with Neurological Diseases or Conditions and Cardiovascular Conditions After Birth, run by Wake Forest University Health Sciences at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 11 years and older
What is being tested?
Active CR
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
200 participants
Where
1 siteUnited States
Study dates
12 Apr 2019to Apr 2028
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 11 years and older
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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).
  • 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) within the last 3 years.
Show all 9Show fewer
  • 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.

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Kenzie Brown contact

336-716-9447

BBRP@wakehealth.edu

United States1 site, 1 recruiting

  • Wake Forest University Health Scienc\ess

    Winston-Salem, North Carolina, 27157

    Kenzie Brown, 336-716-9447, BBRP@wakehealth.edu

    Charles Tegeler, MD

    Recruiting

Other trials in United States

About this study

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.

Read the 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 200 participants will be enrolled. Participants will receive between 4 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 also serve as the primary outcome. Secondary outcomes to be collected include symptom inventories for insomnia (Insomnia Severity Index, ISI; depression (Center for Epidemiological Studies- Depression Scale, CES-D), anxiety (Generalized Anxiety Disorder-7, GAD-7), and stress (Perceived Stress Scale, PSS). Other tertiary measures include traumatic stress (PTSD Checklist for civilians, PCL-C, or military, PCL-M), and overall quality of life (QOLS). 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 and appropriate tertiary 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.

Being tested
Active CR
Keywords
Stress, Neurotechnology, Autonomic Dysregulation, Hyperarousal, Brain electrical activity, Allostasis, HIRREM, Cereset Research, Insomnia, Anxiety
Medical subject headings
Psychophysiologic Disorders, Primary Dysautonomias, Sleep Initiation and Maintenance Disorders, Anxiety Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Active CRDevice

    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.

Study groups in NCT03777267
Study groupRoleWhat they receive
Experimental: Active CRExperimentalFor this single arm, open label, exploratory trial this will be the intervention arm using active CR.
Receives: Device: Active CR

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in Heart Rate Variability

    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.

    Measured: Baseline, and V3 (4-6 weeks after V2)

  2. Change in Baroreflex Sensitivity

    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).

    Measured: Baseline, and V3 (4-6 weeks after V2)

  3. Change in Blood Pressure Variability

    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).

    Measured: Baseline, and V3 (4-6 weeks after V2)

Secondary outcomes (4)

  1. 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.

    Measured: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2)

  2. 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.

    Measured: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2)

  3. 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.

    Measured: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2)

  4. 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.

    Measured: Baseline, V2 (0-14 days after final session), and V3 (4-6 weeks after V2)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Dec 2018
  2. Study start12 Apr 2019
  3. Primary completionApr 2028 (estimated)
  4. Study completionApr 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Supportive care
Allocation
Not applicable
Intervention model
Single group
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 200 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 4 and 12 intervention sessions of Cereset Research consisting of audible tones echoing current brainwave activity.
Masking
None (open label)
Enrolment
200 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03777267
Sponsor's protocol ID
IRB00055280
Status last verified
Jul 2026
First submitted
14 Dec 2018
Last updated
20 Jul 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
Yes
Individual data sharing
No

Publications

  • Hale TS, Smalley SL, Walshaw PD, Hanada G, Macion J, McCracken JT, McGough JJ, Loo SK. Atypical EEG beta asymmetry in adults with ADHD. Neuropsychologia. 2010 Oct;48(12):3532-9. doi: 10.1016/j.neuropsychologia.2010.08.002. Epub 2010 Aug 10.

    PubMed 20705076

  • Hale TS, Smalley SL, Dang J, Hanada G, Macion J, McCracken JT, McGough JJ, Loo SK. ADHD familial loading and abnormal EEG alpha asymmetry in children with ADHD. J Psychiatr Res. 2010 Jul;44(9):605-15. doi: 10.1016/j.jpsychires.2009.11.012. Epub 2009 Dec 16.

    PubMed 20006344

  • Hale TS, Smalley SL, Hanada G, Macion J, McCracken JT, McGough JJ, Loo SK. Atypical alpha asymmetry in adults with ADHD. Neuropsychologia. 2009 Aug;47(10):2082-8. doi: 10.1016/j.neuropsychologia.2009.03.021. Epub 2009 Apr 5.

    PubMed 19467358

  • Lazarev VV, Pontes A, Mitrofanov AA, deAzevedo LC. Interhemispheric asymmetry in EEG photic driving coherence in childhood autism. Clin Neurophysiol. 2010 Feb;121(2):145-52. doi: 10.1016/j.clinph.2009.10.010. Epub 2009 Dec 1.

    PubMed 19951847

  • Stroganova TA, Nygren G, Tsetlin MM, Posikera IN, Gillberg C, Elam M, Orekhova EV. Abnormal EEG lateralization in boys with autism. Clin Neurophysiol. 2007 Aug;118(8):1842-54. doi: 10.1016/j.clinph.2007.05.005. Epub 2007 Jun 19.

    PubMed 17581774

  • Thibodeau R, Jorgensen RS, Kim S. Depression, anxiety, and resting frontal EEG asymmetry: a meta-analytic review. J Abnorm Psychol. 2006 Nov;115(4):715-29. doi: 10.1037/0021-843X.115.4.715.

    PubMed 17100529

  • Avram J, Baltes FR, Miclea M, Miu AC. Frontal EEG activation asymmetry reflects cognitive biases in anxiety: evidence from an emotional face Stroop task. Appl Psychophysiol Biofeedback. 2010 Dec;35(4):285-92. doi: 10.1007/s10484-010-9138-6.

    PubMed 20607389

  • Spironelli C, Penolazzi B, Angrilli A. Dysfunctional hemispheric asymmetry of theta and beta EEG activity during linguistic tasks in developmental dyslexia. Biol Psychol. 2008 Feb;77(2):123-31. doi: 10.1016/j.biopsycho.2007.09.009. Epub 2007 Oct 2.

    PubMed 17997211

  • Moscovitch DA, Santesso DL, Miskovic V, McCabe RE, Antony MM, Schmidt LA. Frontal EEG asymmetry and symptom response to cognitive behavioral therapy in patients with social anxiety disorder. Biol Psychol. 2011 Jul;87(3):379-85. doi: 10.1016/j.biopsycho.2011.04.009. Epub 2011 May 13.

    PubMed 21571033

  • Kemp AH, Griffiths K, Felmingham KL, Shankman SA, Drinkenburg W, Arns M, Clark CR, Bryant RA. Disorder specificity despite comorbidity: resting EEG alpha asymmetry in major depressive disorder and post-traumatic stress disorder. Biol Psychol. 2010 Oct;85(2):350-4. doi: 10.1016/j.biopsycho.2010.08.001. Epub 2010 Aug 11.

    PubMed 20708650

  • Rabe S, Beauducel A, Zollner T, Maercker A, Karl A. Regional brain electrical activity in posttraumatic stress disorder after motor vehicle accident. J Abnorm Psychol. 2006 Nov;115(4):687-98. doi: 10.1037/0021-843X.115.4.687.

    PubMed 17100526

  • Metzger LJ, Paige SR, Carson MA, Lasko NB, Paulus LA, Pitman RK, Orr SP. PTSD arousal and depression symptoms associated with increased right-sided parietal EEG asymmetry. J Abnorm Psychol. 2004 May;113(2):324-9. doi: 10.1037/0021-843X.113.2.324.

    PubMed 15122952

  • Marzano C, Ferrara M, Sforza E, De Gennaro L. Quantitative electroencephalogram (EEG) in insomnia: a new window on pathophysiological mechanisms. Curr Pharm Des. 2008;14(32):3446-55. doi: 10.2174/138161208786549326.

    PubMed 19075720

  • Wolynczyk-Gmaj D, Szelenberger W. Waking EEG in primary insomnia. Acta Neurobiol Exp (Wars). 2011;71(3):387-92. doi: 10.55782/ane-2011-1860.

    PubMed 22068747

  • Riemann D, Spiegelhalder K, Feige B, Voderholzer U, Berger M, Perlis M, Nissen C. The hyperarousal model of insomnia: a review of the concept and its evidence. Sleep Med Rev. 2010 Feb;14(1):19-31. doi: 10.1016/j.smrv.2009.04.002. Epub 2009 May 28.

    PubMed 19481481

Questions about this trial

What is this clinical trial studying?

A study testing Active CR in people with Neurological Diseases or Conditions and Cardiovascular Conditions After Birth, run by Wake Forest University Health Sciences at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Kenzie Brown (336-716-9447, BBRP@wakehealth.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Heart Rate Variability (time frame: Baseline, and V3 (4-6 weeks after V2)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03777267, which also lists 69 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2026; AzTrials last refreshed its copy on 26 Oct 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Keep searching with a free account

You’ve used your 3 free searches for this session. Log in or create a free AzTrials account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in