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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Insomnia
• Intervention / Treatment: Drug: Suvorexant; Drug: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 34
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Jeremy Bigalke; Phone Number: 406-994-2292; Email: jeremy.bigalke@student.montana.edu

Study Locations

• United States
  • Montana
    • Bozeman, Montana, United States, 59717
      • Recruiting
      • Montana State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Drug (Suvorexant); 20 mg of Suvorexant daily (taken orally ~1 hour before bedtime)	Drug: Suvorexant; Insomnia subjects will take a nightly pill of 20 mg Suvorexant for eight weeks.
PLACEBO_COMPARATOR: Placebo; 20 mg of Placebo daily (taken orally ~1 hour before bedtime)	Drug: Placebo; Insomnia subjects will take a nightly pill of 20 mg placebo for eight weeks.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Montana State University
• Collaborators: University of Chicago
• Investigators: Principal Investigator: Jason Carter, PhD, Montana State University

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 18, 2019
• Primary Completion (ANTICIPATED): December 1, 2022
• Study Completion (ANTICIPATED): April 1, 2023

Study Registration Dates

• First Submitted: December 5, 2018
• First Submitted That Met QC Criteria: December 6, 2018
• First Posted (ACTUAL): December 7, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 7, 2021
• Last Update Submitted That Met QC Criteria: October 5, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Sleep Initiation and Maintenance Disorders; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Hypnotics and Sedatives; Sleep Aids, Pharmaceutical; Orexin Receptor Antagonists; Suvorexant
• Other Study ID Numbers: JC101320-FC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes