Exploratory Study of Cereset Research

The primary objective of this open label exploratory study is to evaluate the use of Cereset
Research to improve autonomic cardiovascular regulation in participants with symptoms of
neurological, cardiovascular, and psychophysiological conditions.

Secondary outcomes include evaluating the effect of CR for a variety of self-reported symptom
inventories and functional measures.

Methods:This will be a single site, open label, pilot clinical trial, enrolling people aged
11 or older, who have self-reported symptoms of neurological, cardiovascular, and
psychophysiological conditions. Up to 100 participants will be enrolled so as to gather pilot
data that will help inform regarding feasibility, effect size, and dosing to support future
cohort-specific randomized trials. 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 be 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), and overall quality of life (QOLS). There will be additional inventories for physical
activity (International Physical Activity Questionnaire, IPAQ-SF), and physical activity
satisfaction questions, along with functional measures (blood pressure, drop stick reaction
testing, and grip strength), which will also be secondary outcomes. All measures will be
collected at an enrollment visit (V1), and the intervention will begin 0-14 days thereafter.
Post-intervention data collections will be obtained at 0-21 days (V2) after completion of the
intervention, and 4-8 weeks (V3) after the V2 visit. Mean contrasts will be used to compare
the changes in symptom scores for the primary outcome of insomnia/sleep from V1 to V3, as
well as secondary outcomes/symptom scores, and measures of autonomic cardiovascular
regulation. 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.

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 a neurologic, cardiovascular, or psychophysiological
condition such as ADHD, anxiety, addiction/dependence, Asperger Syndrome, dyslexia,
depression, dementia, cancer, heart attack, migraine, hot flashes, pain,
post-traumatic stress, stroke, or traumatic brain injury, or if they are a caregiver
or first responder.

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.