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

NCT ID: NCT07332442

Last Updated: 2026-01-12

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 250 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2026-02-28
• Study Completion Date: 2030-06-30

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.

Detailed Description

Primary Objective The primary objective of this study is to determine whether raising arousal threshold (ArTH) in OSA will improve response to CPAP therapy in people with OSA, where response includes factors such as adherence, change in executive function (Flanker Inhibitory Control test) and cardiovascular function (flow mediated vasodilatation, an exploratory outcome).

Secondary Objective The secondary objective[s] of this study are to understand the mechanisms by which raising ArTH may improve adherence to CPAP, neurocognitive and cardiovascular function. The mechanisms investigated include sleep duration, depth, CPAP level and tolerance, hypoxia, patient symptoms, biomarkers of neuronal damage, oxidative stress and sympathetic activation.

Conditions

Sleep Apnea; Obstructive Sleep Apnea

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: QUADRUPLE

Study Groups

Eszopiclone

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

Group Type: EXPERIMENTAL

Eszopiclone

Intervention Type: DRUG

3mg for \< 65 and 2mg for ≥ 65 years

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Matched placebo

Interventions

Eszopiclone

3mg for \< 65 and 2mg for ≥ 65 years

Intervention Type: DRUG

Placebo

Matched placebo

Intervention Type: DRUG

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
• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

ResMed Foundation

OTHER

Sponsor Role: collaborator

Yale University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Audrey Zinchuk,, MD, MHS

Role: PRINCIPAL_INVESTIGATOR

Yale University

Locations

Yale Centers for Sleep Medicine

North Haven, Connecticut, United States

Countries

United States

Central Contacts

Andrey Zinchuk, MD, MHS

Role: CONTACT

andrey.zinchuk@yale.edu

475-655-6199

Iouri Kreinin, MD

Role: CONTACT

iouri.kreinin@yale.edu

Other Identifiers

1R01HL179077-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2000040345

Identifier Type: -

Identifier Source: org_study_id