Endotype-Targeted Therapy to Rescue OSA Patients Struggling With CPAP Adherence (TOP-CPAP)

NCT05951023 | Completed Phase 2 FDA Drug

• 2 other identifiers: 190560277-JF-22
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 1

Brief Summary

More than 10% of the US population have obstructive sleep apnea (OSA). Standard of care is therapy with CPAP (continuous positive airway pressure) which virtually eliminates OSA. However, most patients use CPAP only for part of the night (4-5hours) and about 50% patients discontinue CPAP long-term. Alternative therapies are limited, thus many OSA patients remain at risk of OSA sequelae (e.g. sleepiness, memory issues, high blood pressure, etc.). Importantly, different patients get OSA for different reasons, and recent data show that some of the underlying causes of OSA ("endotypes") such as having a low arousal threshold (i.e. waking up easily) are associated with lower CPAP adherence. Using a randomized controlled trial design, this will be the first study using a targeted intervention to manipulate the underlying OSA causes (i.e., giving a safe hypnotic to patients with OSA to increase the arousal threshold) to test the hypothesis that endotype-targeted therapy increases CPAP-adherence in patients who have low but continued CPAP usage. Ultimately, this strategy may improve the care and outcomes of millions of undertreated OSA patients.

Conditions

Obstructive Sleep Apnea

Keywords

Obstructive Sleep Apnea; OSA; Continuous Positive Airway Pressure; CPAP; Adherence; Eszopiclone; Endotype; Arousal Threshold

Outcome Measures

Primary Outcomes (1)

• Mean use per night of continuous positive airway pressure (CPAP)

  Based on device recorded usage

  days 2-14 after initiation of study drugs

Secondary Outcomes (8)

• Alternative measures of CPAP usage

  days 2-14 after initiation of study drugs

• Response Speed

  days 2-14 after initiation of study drugs

• Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SDA) instrument

  days 2-14 after initiation of study drugs

• Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment (SRI) instrument

  days 2-14 after initiation of study drugs

• Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue instrument

  days 2-14 after initiation of study drugs

Other Outcomes (2)

• Sleep Apnea Traits with special focus on arousal threshold

  day1 of study drugs

• Average total sleep time per night

  days 2-14 after initiation of study drugs

Study Arms (2)

Eszopiclone

EXPERIMENTAL

Subjects will be asked to take their study drugs nightly at bedtime and use their CPAP during sleep as much as possible

Drug: Eszopiclone 2 mg

Placebo

PLACEBO COMPARATOR

Subjects will be asked to take their study drugs nightly at bedtime and use their CPAP during sleep as much as possible

Drug: Placebo

Interventions

Eszopiclone 2 mg DRUG

Eszopiclone tablet (encapsulated)

Also known as: Lunesta

Eszopiclone

Placebo DRUG

Sugar capsule manufactured to match encapsulated Eszopiclone

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ages 21-65 years old
• Body Mass Index \<32 kg/m\^2
• Physician diagnosis of OSA (AHI ≥ 10) based on a clinical sleep study within the past 2 years (subjects who report a history of sleep apnea but do not have a sleep study report from the past 2 years available will be offered an overnight home sleep apnea test to verify OSA diagnosis)
• AHI\>5/h on the overnight research sleep study #1
• Subject had the opportunity to use CPAP for at least 1 month
• Continuous positive airway pressure (CPAP) data can be queried remotely and shows usage 0.5-4h/night (based on most recent 30 day period)
• Interest to continue trying CPAP

You may not qualify if:

• "SAVE CPAP Side Effect Score" \>3 (1 point for each: dry mouth, nasal symptoms, CPAP pressure intolerance, claustrophobia, noise problems, soreness/skin irritation, mask fit/leak problems)
• Any high-risk features: Epworth sleepiness score ≥18, safety-critical profession (e.g., commercial driver), prior sleep-related car accident, substantial hypoxemia during sleep \[SpO2\<70% for \>5min\] or awake \[SpO2\<92%\]
• Any uncontrolled medical/psychiatric condition, or safety concern based on MD judgment
• Pregnancy/Breastfeeding (current or planned during the next month)
• Inability to complete study procedures, such as questionnaires that are only available/validated in English
• Other known untreated sleep fragmenting disorder, such as periodic limb movement disorder, or narcolepsy
• Unwilling or unable to withhold CPAP during polysomnography
• Presence of tracheostomy
• Hospitalization within the past 90 days
• Allergy to the study drug
• Regular use of opioids, or benzodiazepines
• Chronically using study drug or other hypnotic
• Significant circadian rhythm disorder or sleepwalking as an adult
• Active illicit substance use or \>3 oz nightly alcohol use
• Prisoners

Sponsors & Collaborators

• University of California, San Diego: lead
• American Academy of Sleep Medicine: collaborator

Study Sites (1)

UC San Diego; Altman Clinical and Translational Research Institute Building

La Jolla, California, 92121, United States

Location

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Eszopiclone

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; 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

• Christopher N Schmickl, MD, PhD

  University of California, San Diego

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Randomized, double-blind, placebo-controlled, parallel trial

Study Record Dates

• First Submitted: June 17, 2023
• First Posted: July 18, 2023
• Study Start: August 31, 2023
• Primary Completion: July 23, 2025
• Study Completion: October 1, 2025
• Last Updated: November 25, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)