Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1R01HL179077-01 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| ResMed Foundation | OTHER |
Not provided
Not provided
Not provided
Not provided
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.
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Eszopiclone | Experimental | 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 |
|
| Placebo | Placebo Comparator | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Eszopiclone | Drug | 3mg for < 65 and 2mg for ≥ 65 years |
| |
| Measure | Description | Time Frame |
|---|---|---|
| CPAP adherence | Mean daily average of CPAP use over 3 months | Daily over 3 months |
| Flanker inhibitory control and attention test | 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. | Baseline, 1-, 2- and 3-months |
| Measure | Description | Time Frame |
|---|---|---|
| Mean Epworth Sleepiness Scale score Scores | Sleep questionnaire of subjective sleepiness. Total score range of 0-24; scores above 10 suggest excessive sleepiness. | Baseline, 1-, 2-and 3-months |
| Mean Functional Outcomes of Sleep Questionnaire (FOSQ) short form score |
| Measure | Description | Time Frame |
|---|---|---|
| Flow mediated vasodilation (FMD) - exploratory | FMD is a standard non-invasive technique for assessing endothelial function. FMD will be obtained using a standard method by a trained RA at the same time of the day after the baseline PSG and the 3-month follow-up. Two-dimensional longitudinal images will be acquired using Doppler ultrasound to assess arterial diameter and flow velocity (resting and hyperemic). Resting blood flow is estimated by time-averaging the pulsed Doppler signal obtained from a mid-vessel sample volume. The blood pressure cuff is then inflated to >50 mmHg above systolic pressure to occlude arterial inflow for 5 minutes. A cuff is then deflated, and a pulse wave and longitudinal images are obtained at 10 seconds and 60 seconds (hyperemia). The FMD is the percent increase in vessel diameter from baseline to hyperemia. |
Inclusion Criteria:
Able to provide informed consent.
Clinically confirmed new diagnosis of OSA:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Andrey Zinchuk, MD, MHS | Contact | 475-655-6199 | andrey.zinchuk@yale.edu | |
| Iouri Kreinin, MD | Contact | iouri.kreinin@yale.edu |
| Name | Affiliation | Role |
|---|---|---|
| Audrey Zinchuk,, MD, MHS | Yale University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Yale Centers for Sleep Medicine | Recruiting | North Haven | Connecticut | 06347 | United States |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D012891 | Sleep Apnea Syndromes |
| D020181 | Sleep Apnea, Obstructive |
| ID | Term |
|---|---|
| D001049 | Apnea |
| D012120 | Respiration Disorders |
| D012140 | Respiratory Tract Diseases |
| D020919 | Sleep Disorders, Intrinsic |
Not provided
Not provided
| ID | Term |
|---|---|
| D000069582 | Eszopiclone |
| ID | Term |
|---|---|
| D010879 | Piperazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D011719 | Pyrazines |
Not provided
Not provided
randomized, double-blind controlled clinical trial with 3 month follow up.
Not provided
Not provided
Not provided
| Placebo |
| Drug |
Matched placebo |
|
Measures how sleepiness affects daily life, with scores ranging from 5-20. Higher scores indicate better functioning and less impairment. |
| Baseline, 1-, 2-and 3-months |
| Mean Insomnia Severity Index score (ISI) Scores | ISI is a validated 7-question survey. The total score range is 0-28 with higher scores indicating more severe insomnia. | Baseline, 1-, 2-and 3-months |
| Mean PROMIS Sleep Disturbance score Scores | T-score mean of 50 and a standard deviation (SD) of 10. Higher scores indicating more sleep disturbance. | Baseline, 1-, 2-and 3-months |
| Mean PROMIS Sleep-Related Impairment score Scores | T-score mean of 50 and a standard deviation (SD) of 10. Higher scores indicating more sleep disturbance. | Baseline, 1-, 2-and 3-months |
| Mean time to complete Trail Making Test (TMT) A and B | Administered on standardized paper form by research associate. Both parts of the Trail Making Test consist of 25 circles distributed over a sheet of paper and participant connect numbers (Part A) and numbers with letters (Part B) in ascending order. Mean time to connect the "trail" in minutes. | Baseline, 1-, 2-and 3-months |
| Mean processing speed of Pattern Comparison Processing Speed Test | Administered by participants via an iPad to assess processing speed. Participants are asked to quickly determine whether two stimuli are the same or not the same. Mean time in seconds. | Baseline, 1-, 2-and 3-months |
| Mean reaction time of Psychomotor vigilance test (PVT) | Administered by participants via a computer to complete psychomotor vigilance task at the same time in the morning. Mean time in minutes to complete assessment of daytime vigilance = 1/reaction-time. | Baseline, 1-, 2-and 3-months |
| Mean percent accuracy of Change Card Sort Test | Administered by participants via an iPad to assess cognitive flexibility and attention. The participant is asked to match a series of picture pairs to a target picture. | Baseline, 1-, 2-and 3-months |
| Mean percent correct recall of Verbal Paired Associates A-B task | Administered by participants via an iPad with audio instructions and feedback to assess recall. The participant is asked to recall A-B verbal paired associates word-pairs. Immediate recall occurs before sleep and delayed recall occurs after sleep. | Baseline and 3-months |
| Mean OSA alleviation at 3 months | Defined as: therapeutic efficacy × adjusted CPAP adherence. The therapeutic efficacy for OSA is "[AHI-baseline - AveAHI-3-months on CPAP] / AHI-baseline" and the adjusted CPAP adherence is objective AveCPAP use / AveSleep time (both in hours) over 3 months | 3 months |
| Mean percent hypoxic burden | Hypoxic burden (HB) is a sleep apnea metric that quantifies the total oxygen deprivation by measuring the depth and duration of blood oxygen drops (desaturations) during sleep, expressed as %-minutes per hour. | Baseline and at the night of CPAP and eszopiclone/placebo initiation: 3 weeks after baseline visit |
| Mean sleep depth score | Sleep depth will be measured by an Odds Ratio Product (ORP), a continuous metric based on quantitative analysis of the EEG power spectra. High values indicate deeper sleep, with a range of 0 - 2.5. | Baseline and at the night of CPAP and eszopiclone/placebo initiation: 3 weeks after baseline visit |
| Arousal intensity | Arousal intensity is measured on a scale between 0 and 9 (most intense) using a validated automated wavelet transformation method (Azarbarizin et al., Sleep 2014) | Baseline and at the night of CPAP and eszopiclone/placebo initiation: 3 weeks after baseline visit |
| Ventilatory burden | The average ventilatory burden per event is defined as the multiplication of the average ventilation during the respiratory event (i.e., event depth) and average duration of respiratory events. The total ventilatory burden (percentage eupnea × min/h) for each participant is defined as the multiplication of respiratory event rate (events/h) and average ventilatory area per event (percentage eupnea × min/event). | Baseline and at the night of CPAP and eszopiclone/placebo initiation: 3 weeks after baseline visit |
| Mean concentration Neurofilament Light Chain (NfL) | Mean concentration NfL (pg/ml) in the blood to assess neuronal injury and damage. | Baseline and 3-months |
| Mean concentration Aβ40 | Mean concentration Aβ40 (pg/ml) in the blood (usually measured as a ratio with Aβ42 (Aβ42/40 ratio) to assess brain amyloid plaque buildup. | Baseline and 3-months |
| Mean concentration F2-isprostane | Mean concentration F2-isprostane (pg/ml) in the blood to assess oxidative stress. | Baseline and 3-months |
| Mean concentration oxidized LDL | Mean concentration oxidized LDL (pg/ml) in the blood to assess oxidative stress. | Baseline and 3-months |
| Mean morning concentration cortisol | Mean concentration cortisol (pg/ml) in the blood to assess autonomic activation. | Baseline and 3-months |
| Mean concentration norepinephrine | Mean concentration norepinephrine (pg/ml) in the blood to assess autonomic activation. | Baseline and 3-months |
| Mean systolic and diastolic blood pressure (BP) | Mean systolic and diastolic blood pressure during a single 24-hour period at baseline and 3-month | Baseline and 3-months |
| Blood pressure variability | Blood pressure variability during a single 24-hour period at baseline and 3-month | Baseline and 3-months |
| Mean nighttime BP dipping | Mean nighttime BP dipping during a single 24-hour period at baseline and 3-month | Baseline and 3-months |
| Mean CPAP pressure over 3 months | Measured nightly from cloud-based remote monitoring adherence system | Assessed daily over 3 months |
| Mean residual AHI over 3 months | Measured nightly from cloud-based remote monitoring adherence system | Assessed daily over 3 months |
| baseline and 3 months |
| D020920 |
| Dyssomnias |
| D012893 | Sleep Wake Disorders |
| D009422 | Nervous System Diseases |
| D011725 |
| Pyridines |