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

Yale University

Status and phase: Not yet enrolling; Phase 3

Conditions: Sleep Apnea; Obstructive Sleep Apnea

Treatments: Drug: Placebo; Drug: Eszopiclone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT07332442

1R01HL179077-01 (U.S. NIH Grant/Contract)

2000040345

Details and patient eligibility

About

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.

Full 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.

Enrollment: 250 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Able to provide informed consent.

• Clinically confirmed new diagnosis of OSA:

  1. Polysomnography AHI ≥ 10 per hour of sleep and/or
  2. 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.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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250 participants in 2 patient groups, including a placebo group

Eszopiclone

Experimental group

Description:

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

Treatment:

Drug: Eszopiclone

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo