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

Overview

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.

Interventions

• Drug Eszopiclone
  3mg for \< 65 and 2mg for ≥ 65 years
• Drug Placebo
  Matched placebo

Primary outcome measures

• CPAP adherence [Time frame: Daily over 3 months]
• Flanker inhibitory control and attention test [Time frame: Baseline, 1-, 2- and 3-months]

Secondary outcome measures (12)

• Mean Epworth Sleepiness Scale score Scores [Time frame: Baseline, 1-, 2-and 3-months]
• Mean Functional Outcomes of Sleep Questionnaire (FOSQ) short form score [Time frame: Baseline, 1-, 2-and 3-months]
• Mean Insomnia Severity Index score (ISI) Scores [Time frame: Baseline, 1-, 2-and 3-months]
• Mean PROMIS Sleep Disturbance score Scores [Time frame: Baseline, 1-, 2-and 3-months]
• Mean PROMIS Sleep-Related Impairment score Scores [Time frame: Baseline, 1-, 2-and 3-months]
• Mean time to complete Trail Making Test (TMT) A and B [Time frame: Baseline, 1-, 2-and 3-months]
• Mean processing speed of Pattern Comparison Processing Speed Test [Time frame: Baseline, 1-, 2-and 3-months]
• Mean reaction time of Psychomotor vigilance test (PVT) [Time frame: Baseline, 1-, 2-and 3-months]
• Mean percent accuracy of Change Card Sort Test [Time frame: Baseline, 1-, 2-and 3-months]
• Mean percent correct recall of Verbal Paired Associates A-B task [Time frame: Baseline and 3-months]
• Mean OSA alleviation at 3 months [Time frame: 3 months]
• Mean percent hypoxic burden [Time frame: Baseline and at the night of CPAP and eszopiclone/placebo initiation: 3 weeks after baseline visit]

Eligibility criteria

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
• 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 .

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Basic science

Study locations

United States · 1 center

• Yale Centers for Sleep Medicine — North Haven

Identifiers

NCT: NCT07332442 · 2000040345 · 1R01HL179077-01

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗