Continuous Positive Airway Pressure, Arousability and Links to Mechanisms in Obstructive Sleep Apnea (CALM-OSA)

The primary objective of this study is to determine whether arousal threshold (ArTH) can help understand why some people respond to CPAP therapy more than others. This will allow us to understand if changing the arousal threshold can improve the effect of CPAP in people with sleep apnea.

Two hundred and fifty participants will be enrolled. After enrollment, a 7-day CPAP mask run-in period will identify those willing to accept CPAP therapy. Those completing the run-in period, will undergo baseline assessments including measures of neurocognitive function, surveys measuring established determinants of CPAP adherence, sleep quality, and daytime symptoms (e.g insomnia, sleepiness); blood biomarkers (e.g neurofilament light [NfL], oxidized LDL); endothelial function assessed by flow-mediated dilation (FMD); 24-hour ambulatory blood pressure monitoring; and in-lab polysomnography (PSG) to characterize OSA-related sleep metrics (e.g., AHI, percent of time with oxygen saturation <90%, sleep depth, hypoxic burden, and arousal intensity), as well as ArTH.

Participants will be randomized to either eszopiclone or placebo and both arms will start and use CPAP therapy for 3 months. The night of starting drug/placebo, participants will undergo a second polysomnography study to evaluate intervention-related changes in ArTH, assess CPAP related changes in sleep metrics, and determine the initial CPAP therapeutic pressure. There are monthly follow up visits assessing symptoms, neurocognitive function, CPAP use, adverse effects and adherence to medication. At the final study visit, repeat assessments of neurocognitive function, blood biomarkers, questionnaires, endothelial function, and blood pressure will be performed.

Participants will receive a stipend (up to $575) and can choose to keep the CPAP device ($800 value) distributed by the research team.

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)
• 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
• History of motor vehicle accidents related to sleepiness and/or motor vehicle “near misses” (e.g. sleepiness during driving or lane changes)
• Active cancer receiving chemotherapy