Continuous Positive Airway Pressure, Arousability and Links to Mechanisms in Obstructive Sleep Apnea

Official Summary

The study design is a randomized, controlled clinical trial to test the hypothesis that arousal threshold (ArTH) will affect how individuals with obstructive sleep apnea (OSA, Apnea-Hypopnea Index (AHI) of 10/hour of higher) respond to CPAP therapy regarding adherence and cognitive function (executive function). Investigators hypothesize that raising ArTH with eszopiclone will improve adherence to CPAP and neurocognitive function with CPAP therapy. Investigators also hypothesize that a lower baseline ArTH is associated with worse CPAP adherence, while a higher baseline ArTH is associated with improved neurocognitive outcomes with CPAP therapy.

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 250 participants

Study Arms

• Eszopiclone (EXPERIMENTAL)
  Participants will receive eszopiclone the night of the laboratory split-night polysomnography (PSG, sleep monitoring with and without CPAP therapy). Following polysomnography, participants continue with eszopiclone and CPAP therapy
• Placebo (PLACEBO_COMPARATOR)
  Participants will receive placebo the night of the laboratory split-night polysomnography (PSG, sleep monitoring with and without CPAP therapy). Following polysomnography, participants continue with placebo and CPAP therapy

Interventions

• DRUG: Eszopiclone — 3mg for \< 65 and 2mg for ≥ 65 years
• DRUG: Placebo — Matched placebo

Primary Outcomes

• CPAP adherence (Daily over 3 months)
• Flanker inhibitory control and attention test (Baseline, 1-, 2- and 3-months)

Secondary Outcomes

• Mean Epworth Sleepiness Scale score Scores (Baseline, 1-, 2-and 3-months)
• Mean Functional Outcomes of Sleep Questionnaire (FOSQ) short form score (Baseline, 1-, 2-and 3-months)
• Mean Insomnia Severity Index score (ISI) Scores (Baseline, 1-, 2-and 3-months)
• Mean PROMIS Sleep Disturbance score Scores (Baseline, 1-, 2-and 3-months)
• Mean PROMIS Sleep-Related Impairment score Scores (Baseline, 1-, 2-and 3-months)

Eligibility Criteria

Inclusion Criteria:

* Able to provide informed consent.
* Clinically confirmed new diagnosis of OSA:

  1. Polysomnography AHI ≥ 10 per hour of sleep and/or
  2. Home sleep apnea testing, respiratory even index, REI ≥ 10 per hour of recording

Exclusion Criteria:

* Known non-OSA related conditions associated with sleep-disordered breathing (e.g., a central disorder of hypersomnolence, neurological, neuromuscular, or pulmonary disorder)
* Use of sleep-inducing medications (e.g., other non-benzodiazepine sedative hypnotic-drugs \[e.g., zoldpidem\], benzodiazepines, non-selective antihistamines, trazodone, opiates, barbituates)
* Known hypersensitivity reaction to eszopiclone
* Contraindications to its use based on medical history or function (e.g., dizziness at baseline or established mobility problems or imbalance)
* History of complex sleep behaviors (e.g., NREM or REM parasomnias)
* Concomitant use of ≥ 2 servings of alcohol per night or other CNS depressant for 2 weeks prior or throughout the study
* Sleep opportunity of less than 7 hours
* Severe active depression or other mental health disorders (e.g., schizophrenia, bipolar disorder, personality disorder).
* History of sleep-walking, sleep-driving, and engaging in other activities while not fully awake
* History of motor vehicle accidents related to sleepiness and/or motor vehicle "near misses" (e.g. sleepiness during driving or lane changes)
* Severe hepatic impairment (liver function tests 2 X the upper limit of normal)
* Unstable medical condition (e.g., decompensated heart failure, end-stage chronic obstructive pulmonary disease, end-stage renal disease)
* Females of childbearing potential who are pregnant, breastfeeding, or intend to become pregnant, and women who are in the process of egg donation .

Trial Locations

• Yale Centers for Sleep Medicine, North Haven, Connecticut, United States

Contact Information

• Andrey Zinchuk, MD, MHS — CONTACT
  Phone: 475-655-6199
  Email: andrey.zinchuk@yale.edu
• Iouri Kreinin, MD — CONTACT
  Email: iouri.kreinin@yale.edu

Study Officials

• Audrey Zinchuk,, MD, MHS — PRINCIPAL_INVESTIGATOR
  Yale University

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