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

NCT07332442 | Recruiting Phase 3 FDA Drug

• 2 other identifiers: 20000403451R01HL179077-01
• Study Type: interventional
• Target: 250
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Sleep Apnea; Obstructive Sleep Apnea

Keywords

Continuous Positive Airway Pressure (CPAP); sleep apnea; hypnotic; mechanism; arousability

Outcome Measures

Primary Outcomes (2)

• CPAP adherence

  Mean daily average of CPAP use over 3 months

  Daily over 3 months

• Flanker inhibitory control and attention test

  Executive function is assessed using the validated NIH Toolbox Cognition Battery's Flanker inhibitory control and attention test. In a Flanker task, participants are required to indicate the left-right orientation of a centrally presented stimulus while inhibiting attention to the potentially incongruent stimuli that surround it (i.e., the flankers, typically two on either side). Primary outcome is the overall percent of correct responses in incongruent trials.

  Baseline, 1-, 2- and 3-months

Secondary Outcomes (26)

• 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

Other Outcomes (1)

• Flow mediated vasodilation (FMD) - exploratory

  baseline and 3 months

Study Arms (2)

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

Drug: Eszopiclone

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

Drug: Placebo

Interventions

Eszopiclone DRUG

3mg for \< 65 and 2mg for ≥ 65 years

Eszopiclone

Placebo DRUG

Matched placebo

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to provide informed consent.
• Clinically confirmed new diagnosis of OSA:
• Polysomnography AHI ≥ 10 per hour of sleep and/or
• Home sleep apnea testing, respiratory even index, REI ≥ 10 per hour of recording

You may not qualify if:

• 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 .

Sponsors & Collaborators

• Yale University: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator
• ResMed Foundation: collaborator

Study Sites (1)

Yale Centers for Sleep Medicine

North Haven, Connecticut, 06347, United States

RECRUITING

MeSH Terms

Conditions

Sleep Apnea Syndromes; Sleep Apnea, Obstructive

Interventions

Eszopiclone

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Pyridines

Study Officials

• Audrey Zinchuk,, MD, MHS

  Yale University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrey Zinchuk, MD, MHS

CONTACT

475-655-6199; andrey.zinchuk@yale.edu

Iouri Kreinin, MD

CONTACT

iouri.kreinin@yale.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: randomized, double-blind controlled clinical trial with 3 month follow up.

Study Record Dates

• First Submitted: December 23, 2025
• First Posted: January 12, 2026
• Study Start: May 1, 2026
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): June 1, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)