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

Study Overview
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Brief Summary
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This study aims to evaluate the effect of Suvorexant on sympathetic nerve activity and baroreflex function in subject with chronic insomnia. The investigator's central hypothesis is that Suvorexant will reduce sympathetic nerve activity and improve baroreflex function when compared to placebo.

Detailed Description
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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.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study to Determine the Effect of Suvorexant (Belsomra®) on Sympathetic Neural Activity and Baroreflex Function in Patients With Chronic Insomnia

Conditions
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Chronic Insomnia

Intervention / Treatment
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* Drug: Suvorexant
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Minimum 3 months of clinically diagnosed insomnia Body mass index ≤35 kg/m2 Insomnia Severity Index (ISI) > 7 arbitrary units (i.e., mild-to-severe insomnia) 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 > 30 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 ≥ 30 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 or antianxiety), hypnotic, stimulant or analgesic medication (except occasional non-narcotic analgesics) 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Drug (Suvorexant)<br>20 mg of Suvorexant daily (taken orally  1 hour before bedtime) | Drug: Suvorexant<br>* Insomnia subjects will take a nightly pill of 20 mg Suvorexant for eight weeks.<br>|
| Placebo Comparator: Placebo<br>20 mg of Placebo daily (taken orally  1 hour before bedtime) | Drug: Placebo<br>* Insomnia subjects will take a nightly pill of 20 mg placebo for eight weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sympathetic nerve activity | Direct recordings of muscle sympathetic nerve activity from the peroneal nerve using a microelectrode. | 8 weeks | 
| Baroreflex sensitivity | The linear relationship between changes in beat-to-beat diastolic arterial pressure and changes in sympathetic nerve activity. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sympathetic reactivity | The change in muscle sympathetic nerve activity during a cold pressor test. | 8 weeks | 
| Home sleep quality: Wrist actigraphy | Wrist actigraphy will be used to to determine the quality of sleep, with a primary focus on sleep efficiency. | 8 weeks | 
| Laboratory sleep quality: Polysomnography | Polysomnography will be used to determine the quality of sleep, with a primary focus on sleep efficiency. | 8 week |