Clinical trial NCT05067088: Novel physIologiC prEdictors of Positive Airway Pressure Effectiveness
Official title: Novel physIologiC prEdictors of Positive Airway Pressure Effectiveness: NICEPAP Study Prospective Cohort
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Obstructive Sleep Apnea
Keywords: 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
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2021-10-05
Enrollment: 267
Sex: ALL
Minimum age (years): 19
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The participants will be drawn from the clinical population of patients referred for evaluation to the Yale New Haven Hospital Sleep Center. Currently, 38% of patients at YNHH with diagnosis of OSA are women, 65% are White, 12% Black, 10% Hispanic, 1% Asian, 1% Pacific Islander and remainder selecting other or unknown classification. We expect a similar proportion of enrolled subjects. Inclusion of vulnerable population subjects such prisoners or institutionalized individuals will be rare as these patients are infrequently evaluated sleep medicine clinics, however, they will not be excluded. Subjects who are undocumented immigrants to the U.S. will not be excluded and will undergo an informed consent process individualized in each encounter. Inclusion/exclusion criteria are noted above.

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Age of \>18 years
2. Newly diagnosed OSA naïve to CPAP
3. Apnea hypopnea index (AHI) ≥5/hr on in-laboratory polysomnography or home sleep test acquired and scored using standard criteria(59)
4. Referred for CPAP adherence management at Yale New Haven Hospital Sleep Center

Exclusion Criteria:

1. Need for supplemental oxygen
2. Central apnea index comprising \>50% of the AHI
3. Treatment recommendation with another modality (e.g., Bilevel PAP, Adaptive Servo-Ventilation, Automatic Volume Pressure Assured Pressure Support)
4. A referral for a sleep disorder other than OSA (i.e., narcolepsy, sleep related movement disorder, circadian rhythm sleep-wake disorder)
5. Prior CPAP or Auto-CPAP use over the past 3 years
6. Unstable medical or mental health condition (e.g., decompensated heart failure, end-stage chronic obstructive pulmonary disease, end stage renal disease, psychosis)
7. Inability to participate in the informed consent process (e.g., cognitive impairment)
8. Pregnancy
9. 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)

Primary outcomes:
measure: CPAP adherence
timeFrame: 6 months
measure: CPAP efficacy
timeFrame: 6 months
measure: OSA related quality of life measured by Functional Outcomes of Sleep Questionnaire (FOSQ) short form
timeFrame: 6 months
Secondary outcomes:
measure: CPAP adherence (dichotomous)
timeFrame: 3 months
measure: CPAP adherence
timeFrame: 1 month
measure: CPAP adherence
timeFrame: 12 months
measure: CPAP efficacy (dichotomous)
timeFrame: 6 months
measure: Sleep quality: Patient-Reported Outcomes Measurement Information System (PROMIS) scores
timeFrame: 6 months
measure: Sleep related impairment: Patient-Reported Outcomes Measurement Information System (PROMIS) scores
timeFrame: 6 months
measure: Insomnia: Insomnia Severity Index (ISI)
timeFrame: 6 months
measure: Epworth sleepiness scale
timeFrame: 6 months
measure: Anxiety: Hospital Anxiety and Depression Scale - Anxiety subscale scores
timeFrame: 6 months
measure: Depression: Hospital Anxiety and Depression Scale - Depression subscale scores
timeFrame: 6 months
measure: Attention
timeFrame: 6 months
Other outcomes:
Locations:
city: North Haven
country: United States
facility: Yale New Haven Hospital Sleep Center
state: Connecticut
Study officials:
affiliation: Yale University
name: Andrey Zinchuk, MD, MHS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zinchuk A, Edwards BA, Jeon S, Koo BB, Concato J, Sands S, Wellman A, Yaggi HK. Prevalence, Associated Clinical Features, and Impact on Continuous Positive Airway Pressure Use of a Low Respiratory Arousal Threshold Among Male United States Veterans With Obstructive Sleep Apnea. J Clin Sleep Med. 2018 May 15;14(5):809-817. doi: 10.5664/jcsm.7112.
citation: Zinchuk AV, Redeker NS, Chu JH, Liang J, Stepnowsky C, Brandt CA, Bravata DM, Wellman A, Sands SA, Yaggi HK. Physiological Traits and Adherence to Obstructive Sleep Apnea Treatment in Patients with Stroke. Am J Respir Crit Care Med. 2020 Jun 15;201(12):1568-1572. doi: 10.1164/rccm.201911-2203LE. No abstract available.
citation: Zinchuk AV, Chu JH, Liang J, Celik Y, Op de Beeck S, Redeker NS, Wellman A, Yaggi HK, Peker Y, Sands SA. Physiological Traits and Adherence to Sleep Apnea Therapy in Individuals with Coronary Artery Disease. Am J Respir Crit Care Med. 2021 Sep 15;204(6):703-712. doi: 10.1164/rccm.202101-0055OC.