Novel physIologiC prEdictors of Positive Airway Pressure Effectiveness

Study Overview
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Brief Summary
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Millions of Americans suffer from high blood pressure, diabetes, strokes and motor vehicle accidents due to ineffective treatment of obstructive sleep apnea (OSA). Our preliminary data suggest that physiological causes of OSA such as easy arousability (low arousal threshold) or unstable breathing control (high loop gain) may influence effectiveness of OSA's most common treatment, continuous positive airway pressure (CPAP). The NICE-PAP study will examine how the physiologic traits that cause OSA in each individual impact CPAP effectiveness and can lead to personalized OSA treatments that improve patient lives.

Detailed Description
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Most patients with OSA who are prescribed the gold-standard therapy, CPAP, are ineffectively treated. This is due to 1) poor CPAP adherence, 2) high residual apnea in 20% of users (low efficacy) and 3) inconsistent symptom improvement. To improve CPAP effectiveness, we propose to address novel physiologic targets that cause OSA in each individual: arousability (arousal threshold), ventilatory control sensitivity (loop gain) and pharyngeal muscle compensation. Our overall objective is to determine the contribution of these traits to CPAP effectiveness independently of established biological, psychological and social predictors. This study leverages state-of-the art sleep study analysis tools and validated measures of the determinants of CPAP effectiveness to create a pragmatic, prospective cohort (n=267) of OSA patients. This unique dataset will help determine whether physiologic causes of OSA influence CPAP adherence, efficacy, sleep quality, symptoms, function and quality of life. The results will inform design and conduct of a randomized clinical trial designed to modify physiologic traits such as easy arousability to improve CPAP effectiveness and other patient-centered outcomes in OSA patients.

Official Title
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Novel physIologiC prEdictors of Positive Airway Pressure Effectiveness: NICEPAP Study Prospective Cohort

Conditions
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Obstructive Sleep Apnea

Intervention / Treatment
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* Other: CPAP (all patients receive CPAP as part of routine clinical care)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of >18 years Newly diagnosed OSA naïve to CPAP Apnea hypopnea index (AHI) ≥5/hr on in-laboratory polysomnography or home sleep test acquired and scored using standard criteria(59) Referred for CPAP adherence management at Yale New Haven Hospital Sleep Center Exclusion Criteria: Need for supplemental oxygen Central apnea index comprising >50% of the AHI Treatment recommendation with another modality (e.g., Bilevel PAP, Adaptive Servo-Ventilation, Automatic Volume Pressure Assured Pressure Support) A referral for a sleep disorder other than OSA (i.e., narcolepsy, sleep related movement disorder, circadian rhythm sleep-wake disorder) Prior CPAP or Auto-CPAP use over the past 3 years Unstable medical or mental health condition (e.g., decompensated heart failure, end-stage chronic obstructive pulmonary disease, end stage renal disease, psychosis) Inability to participate in the informed consent process (e.g., cognitive impairment) Pregnancy Non-English language use as only means of communication (because the research budget does not provide adequate resources to ensure that the needs of non-English speaking patients can be adequately addressed)

Ages Eligible for Study
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Minimum Age: 19 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Intervention/Treatment |
| --- |
|Other: CPAP (all patients receive CPAP as part of routine clinical care)|Continuous positive airway pressure|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CPAP adherence | average daily CPAP use (hours/night) | 6 months | 
| CPAP efficacy | average daily residual apnea hypopnea index on CPAP (events/hour) | 6 months | 
| OSA related quality of life measured by Functional Outcomes of Sleep Questionnaire (FOSQ) short form | FOSQ short form average scores, Range 0 - 5, higher scores reflect worse quality of life and function. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| CPAP adherence (dichotomous) | dichotomized measure of >4 hours/night for >70% of nights | 3 months | 
| CPAP adherence | average daily CPAP use (hours/night) | 1 month | 
| CPAP adherence | average daily CPAP use (hours/night) | 12 months | 
| CPAP efficacy (dichotomous) | residual AHI >=10/hour | 6 months | 
| Sleep quality: Patient-Reported Outcomes Measurement Information System (PROMIS) scores | PROMIS scores, Range 0 - 40, higher scores reflect worse quality | 6 months | 
| Sleep related impairment: Patient-Reported Outcomes Measurement Information System (PROMIS) scores | PROMIS - impairment scores, range 0 - 40, higher scores reflect greater impairment | 6 months | 
| Insomnia: Insomnia Severity Index (ISI) | ISI scores, Range 0 - 28; higher scores reflect higher insomnia burden/severity | 6 months | 
| Epworth sleepiness scale | Epworth sleepiness scale scores, Range 0 - 24; higher scores signify greater sleepiness | 6 months | 
| Anxiety: Hospital Anxiety and Depression Scale - Anxiety subscale scores | Hospital Anxiety and Depression Scale - Anxiety subscale scores range 0 - 21; higher scores signify greater anxiety symptoms | 6 months | 
| Depression: Hospital Anxiety and Depression Scale - Depression subscale scores | Hospital Anxiety and Depression Scale - Depression subscale scores, Range 0 - 21; higher scores signify greater depression symptoms | 6 months | 
| Attention | median reaction time and mean slowest 10% reaction time from a 5-min smartphone-based psychomotor vigilance test. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Continuous positive airway pressure (CPAP), Physiologic sleep apnea traits (endotypes), CPAP adherence, CPAP efficacy, Patient-centered sleep apnea outcomes, Precision medicine, Arousal threshold, Loop gain, Pharyngeal collapsibility, Pharyngeal muscle compensation