Continuous Positive Airway Pressure, Arousability and Links to Mechanisms in Obstructive Sleep Apnea
Overview
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Yale University
- Enrollment
- 250
- Locations
- 1
- Primary Endpoint
- CPAP adherence
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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
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)
Arms & Interventions
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
Intervention: Eszopiclone (Drug)
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
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
CPAP adherence
Time Frame: Daily over 3 months
Mean daily average of CPAP use over 3 months
Flanker inhibitory control and attention test
Time Frame: Baseline, 1-, 2- and 3-months
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.
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 reaction time of Psychomotor vigilance test (PVT)(Baseline, 1-, 2-and 3-months)
- Mean PROMIS Sleep-Related Impairment score Scores(Baseline, 1-, 2-and 3-months)
- Mean processing speed of Pattern Comparison Processing Speed Test(Baseline, 1-, 2-and 3-months)
- Mean time to complete Trail Making Test (TMT) A and B(Baseline, 1-, 2-and 3-months)
- Mean percent accuracy of Change Card Sort Test(Baseline, 1-, 2-and 3-months)
- Mean percent correct recall of Verbal Paired Associates A-B task(Baseline and 3-months)
- Mean OSA alleviation at 3 months(3 months)
- Mean percent hypoxic burden(Baseline and at the night of CPAP and eszopiclone/placebo initiation: 3 weeks after baseline visit)
- Mean sleep depth score(Baseline and at the night of CPAP and eszopiclone/placebo initiation: 3 weeks after baseline visit)
- Arousal intensity(Baseline and at the night of CPAP and eszopiclone/placebo initiation: 3 weeks after baseline visit)
- Ventilatory burden(Baseline and at the night of CPAP and eszopiclone/placebo initiation: 3 weeks after baseline visit)
- Mean concentration Neurofilament Light Chain (NfL)(Baseline and 3-months)
- Mean concentration Aβ40(Baseline and 3-months)
- Mean concentration F2-isprostane(Baseline and 3-months)
- Mean concentration oxidized LDL(Baseline and 3-months)
- Mean morning concentration cortisol(Baseline and 3-months)
- Mean concentration norepinephrine(Baseline and 3-months)
- Mean systolic and diastolic blood pressure (BP)(Baseline and 3-months)
- Blood pressure variability(Baseline and 3-months)
- Mean nighttime BP dipping(Baseline and 3-months)
- Mean CPAP pressure over 3 months(Assessed daily over 3 months)
- Mean residual AHI over 3 months(Assessed daily over 3 months)