Impact of Suvorexant on Sympathetic Nerve Activity and Baroreflex Function in Chronic Insomnia

This study will utilize a randomized, double-blind, placebo-controlled experimental approach
to determine the effects of 8-wk treatment with Suvorexant (Belsomra®) on sympathetic nerve
activity and baroreflex function in male and female subjects with chronic insomnia. The study
will utilize established techniques for assessing sleep (polysomnography), blood pressure
(sphygmomanometer and beat-to-beat finger plethysmography), and peripheral sympathetic nerve
activity (microneurography). The study will stratify enrollment based upon both age and sex
(i.e., male vs. female) because these two covariates are known to influence sympathetic nerve
activity and baroreflex function.

Inclusion Criteria:

- Minimum 3 months of clinically diagnosed insomnia

- Body mass index ≤35 kg/m2

- Insomnia Severity Index (ISI) > 14 arbitrary units (i.e., moderate-to-severe insomnia)

- Pittsburgh Sleep Quality Index (PSQI) > 5 arbitrary units

- Habitual self-report and objectively-assessed (i.e., 14-day actigraphy) sleep duration
of <6.5 hours

- Pre-menopausal women must have regular menstrual cycles (~26-30 day cycles) and will
be scheduled for microneurography 2-7 days after menstruation to consistently test
during the early follicular phase (or low-hormone phase in women on contraceptives)

Exclusion Criteria:

- Current or prior treatment of Suvorexant.

- Obstructive sleep apnea defined as an apnea-hypopnea index > 15 using an FDA approved
home sleep apnea screening devices as used in routine clinical practice.

- Participants without evidence of clinically significant obstructive sleep apnea on the
screening test will undergo an overnight in-laboratory polysomnography to confirm
absence of sleep apnea (apnea-hypopnea index of ≥ 10 episodes per hour) and to exclude
other sleep disorders (e.g. periodic limb movement arousal index of ≥ 5 episodes per
hour)

- Circadian rhythm sleep disorders

- History of meeting DSM-V criteria of major psychiatric disorder

- Have been clinically-diagnosed with diabetes, cardiovascular disease, or any other
unstable or serious medical condition.

- Current, or use within past month, of psychoactive (other than stable treatment with
antidepressant), hypnotic, stimulant or analgesic medication (except occasional
non-narcotic analgesics), beta blockers, or alpha blockers

- Shift work or other types of self-imposed irregular sleep schedules

- Habitual smoking (6 or more cigarettes per week)

- Habitual alcohol consumption (more than 2 alcoholic drinks per day)

- Breastfeeding or pregnancy