HIRREM for Pre-Hypertension

This will be a randomized, single site, controlled, pilot clinical trial, to evaluate the
effects of in-office use of a closed-loop, allostatic, acoustic stimulation neurotechnology
(High-resolution, relational, resonance-based, electroencephalic mirroring; HIRREM), compared
with acoustic stimulation not linked to brainwaves (ambient nature sounds). Assuming a
potential drop-out rate of 20%, up to 24 subjects will be enrolled to achieve a goal of
having at least 20 subjects (10 per group) complete the study, per protocol. Patients who
have blood pressures between 120-139 mm/Hg systolic, and/or 80-89 mm/Hg diastolic, as
documented by their health care providers on two separate occasions, and no other exclusions,
will be randomly assigned to receive either 8-16 sessions of either acoustic stimulation
linked to brainwave activity (HCC), or acoustic stimulation not linked to brainwave activity
(NCC), over a maximum of 4 weeks, with both groups continuing their current care throughout.
There will be pre- and post-intervention data collection to include systolic and diastolic
BP, and many secondary outcome measures including measures of autonomic cardiovascular
regulation (continuous recording of BP and HR for calculation of measure of HRV and BRS),
behavioral symptom outcomes (ISI, PSQI, ESS, CES-D, GAD-7, PCL-C, PSS), quality of life
measure (QOLS), alcohol use (Audit C), and function performance measures (drop stick reaction
testing, and grip strength). All measures will be collected at an enrollment visit (V1), and
the intervention will begin 1-14 days later. BP and HR recordings will also be repeated prior
to the start of the 7th session. Post-intervention data collections will be obtained at 1-7
days (V2), 4-6 weeks (V3, primary outcome), and 12-14 weeks (V4) following completion of the
intervention. The primary outcome will be differential change in the systolic and diastolic
BP from V1 to V3. Additional follow up (V4) will evaluate durability of effects. Following
V4, those in the NCC group will be offered the opportunity to cross over to receive a course
of HCC, and will continue to be followed for data collections at 1-7 days (V5), 4-6 weeks
(V6), and 12-14 weeks (V7) after completing their crossover HCC sessions. Linear mixed models
(LMMs) will be used to contrast longitudinal changes in systolic and diastolic blood pressure
between the HCC and NCC groups. Mean contrasts will be used to compare the changes in blood
pressures between groups from V1 to V3, our primary test of efficacy. Additional mean
contrasts will be constructed to evaluate the consistency of any benefit of HIRREM through
subsequent visits beyond V3. Comparisons of changes in all secondary outcomes will be
assessed in a similar fashion.

Inclusion Criteria:

- Men and women, ≥ 18 years of age, with pre-hypertension, who have systolic BP ranging
from 120-139 mm/Hg, or who have diastolic BP ranging from 80-89 mm/Hg.

Exclusion Criteria:

- Blood pressure values that are outside of the range for prehypertension at the
enrollment visit.

- 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 at a time.

- Prior diagnosis of hypertension.

- Ongoing need for medical treatment for hypertension, or for the use of medications
commonly used for treatment of hypertension.

- Known cardiovascular disease.

- Known seizure disorder.

- Known or anticipated pregnancy (females of childbearing age 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.

- Anticipated and ongoing use of recreational drugs, alcohol, or energy drinks

- Ongoing need for treatment with thyroid medications.