Novel physIologiC prEdictors of Positive Airway Pressure Effectiveness (NICEPAP)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Obstructive Sleep Apnea
• Intervention / Treatment: Other: CPAP (all patients receive CPAP as part of routine clinical care)

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.

• Study Type: Observational
• Enrollment (Estimated): 267

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • North Haven, Connecticut, United States, 06473
      • Yale New Haven Hospital Sleep Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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)

Study Plan

How is the study designed?

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Andrey Zinchuk, MD, MHS, Yale University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2022
• Primary Completion (Estimated): January 30, 2026
• Study Completion (Estimated): August 28, 2026

Study Registration Dates

• First Submitted: September 22, 2021
• First Submitted That Met QC Criteria: September 22, 2021
• First Posted (Actual): October 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: August 1, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Keywords: Precision medicine; Continuous positive airway pressure (CPAP); Loop gain; CPAP adherence; Arousal threshold; Physiologic sleep apnea traits (endotypes); CPAP efficacy; Patient-centered sleep apnea outcomes; Pharyngeal collapsibility; Pharyngeal muscle compensation
• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Wake Disorders; Apnea; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Apnea Syndromes; Sleep Apnea, Obstructive
• Other Study ID Numbers: 2000024615; 1K23HL159259-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No