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

Sponsor

University of California, San Diego (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05951023

Collaborator

American Academy of Sleep Medicine (Other)

Enrollment

Location

Arms

Anticipated Duration (Months)

2.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Obstructive Sleep Apnea	Drug: Eszopiclone 2 mg Drug: Placebo	Phase 2

Detailed Description

This double-blind, randomized, placebo-controlled, single-center, phase II trial, will test if endotype-targeted drug therapy increases CPAP adherence. Patients with low CPAP adherence (i.e. CPAP use 0.5-4h/night) will be randomized in parallel to CPAP+Eszopiclone vs CPAP+Placebo for 2 weeks. The primary outcome is mean TimeOnCPAP/night on days 2-14 after initiation of study drugs.

Aim 1: To test the effect of eszopiclone on CPAP usage in unselected OSA patients with low CPAP adherence.

Hypothesis 1: Eszopiclone improves CPAP usage more than placebo.

Aim 2: To test the effect of eszopiclone on CPAP usage in OSA patients with a low vs a high arousal threshold (ArTH) endotype.

Hypothesis 2: Eszopiclone improves CPAP usage substantially more in OSA patients with a low vs a high ArTH.

Further, this study will explore the mechanisms through which eszopiclone may affect CPAP usage, the effect of eszopiclone on underlying sleep apnea severity, and if the intervention and its potential effects on adherence translate into changes in clinically important outcomes (i.e., vigilance and sleepiness).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

50 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Randomized, double-blind, placebo-controlled, parallel trialRandomized, double-blind, placebo-controlled, parallel trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Endotype-Targeted Therapy to Rescue OSA Patients Struggling With CPAP Adherence (TOP-CPAP): a Pilot Trial

Anticipated Study Start Date :

Aug 1, 2023

Anticipated Primary Completion Date :

Nov 30, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Eszopiclone 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 Eszopiclone tablet (encapsulated) Other Names: Lunesta
Placebo Comparator: Placebo Subjects will be asked to take their study drugs nightly at bedtime and use their CPAP during sleep as much as possible	Drug: Placebo Sugar capsule manufactured to match encapsulated Eszopiclone

Arm

Intervention/Treatment

Experimental: Eszopiclone

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

Eszopiclone tablet (encapsulated)

Other Names:

Lunesta

Placebo Comparator: Placebo

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

Drug: Placebo

Sugar capsule manufactured to match encapsulated Eszopiclone

Outcome Measures

Primary Outcome Measures

Mean use per night of continuous positive airway pressure (CPAP) [days 2-14 after initiation of study drugs]
Based on device recorded usage

Secondary Outcome Measures

Alternative measures of CPAP usage [days 2-14 after initiation of study drugs]
E.g. percentage of nights with CPAP >4h
Response Speed [days 2-14 after initiation of study drugs]
Based on 10-minute Psychomotor vigilance task (PVT)
Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep Disturbance (SDA) instrument [days 2-14 after initiation of study drugs]
Based on response pattern scoring, the PROMIS 8-item SDA score will be converted into a T-score with a mean of 50 (reflecting the average for the United States general population) and a standard deviation of 10. Higher t-scores reflect greater sleep disturbance.
Patient-Reported Outcomes Measurement Information System (PROMIS) Sleep-Related Impairment (SRI) instrument [days 2-14 after initiation of study drugs]
Based on response pattern scoring, the PROMIS 8-item SRI score will be converted into a T-score with a mean of 50 (reflecting the average for the United States general population) and a standard deviation of 10. Higher t-scores reflect greater sleep-related impairment.
Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue instrument [days 2-14 after initiation of study drugs]
Based on response pattern scoring, the PROMIS 8-item Fatigue score will be converted into a T-score with a mean of 50 (reflecting the average for the United States general population) and a standard deviation of 10. Higher t-scores reflect greater sleep-related impairment.
Epworth Sleepiness Scale (ESS) [days 2-14 after initiation of study drugs]
The ESS is an 8-item instrument assessing the likelihood of dozing off in 8 different situations with points for each item ranging from 0 to 3 (0 = would never doze off; 3 = high chance of dozing off). The points for each item are summed up, thus the total score ranges from 0 to 24, with higher ESS scores indicating greater sleepiness.
Apnea Hypopnea Index [day1 of study drugs]
The AHI is a measure of sleep apnea severity and is defined as the number of apneas and hypopneas per hour of sleep.
Mean Blood Pressure (mmHg) [day 14 after initiation of study drugs]
Average of two in-office blood pressure measurements

Other Outcome Measures

Sleep Apnea Traits with special focus on arousal threshold [day1 of study drugs]
Quantified from routine polysomnography data.
Average total sleep time per night [days 2-14 after initiation of study drugs]
Based on actigraphy

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

Exclusion Criteria:

"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
Cognitive impairment, unable to provide consent, or unable to carry out research procedures
Safety concern based on MD judgment