Continuous Positive Airway Pressure, Arousability and Links to Mechanisms in Obstructive Sleep Apnea
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 250
- 试验地点
- 1
- 主要终点
- CPAP adherence
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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 .
研究组 & 干预措施
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
干预措施: Placebo (Drug)
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
干预措施: Eszopiclone (Drug)
结局指标
主要结局
CPAP adherence
时间窗: Daily over 3 months
Mean daily average of CPAP use over 3 months
Flanker inhibitory control and attention test
时间窗: 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.
次要结局
- 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)