Novel physIologiC prEdictors of Positive Airway Pressure Effectiveness

Obstructive Sleep Apnea Clinical Trial

— NICEPAP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05067088
• Other study ID #: 2000024615
• Secondary ID: 1K23HL159259-01
• Status: Recruiting
• Start date: January 1, 2022
• Est. completion date: March 31, 2025

Study information

• Verified date: March 2024
• Source: Yale University
• Contact: Andrey Zinchuk, MD, MHS
• Phone: 475-655-6199
• Email: andrey.zinchuk[@]yale.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 267
• Est. completion date: March 31, 2025
• Est. primary completion date: September 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 19 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Other:
• CPAP (all patients receive CPAP as part of routine clinical care)
Continuous positive airway pressure

Locations

Country	Name	City	State
United States	Yale New Haven Hospital Sleep Center	North Haven	Connecticut

Sponsors (2)

Lead Sponsor	Collaborator
Yale University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CPAP adherence	average daily CPAP use (hours/night)	6 months
Primary	CPAP efficacy	average daily residual apnea hypopnea index on CPAP (events/hour)	6 months
Primary	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	CPAP adherence (dichotomous)	dichotomized measure of >4 hours/night for >70% of nights	3 months
Secondary	CPAP adherence	average daily CPAP use (hours/night)	1 month
Secondary	CPAP adherence	average daily CPAP use (hours/night)	12 months
Secondary	CPAP efficacy (dichotomous)	residual AHI >=10/hour	6 months
Secondary	Sleep quality: Patient-Reported Outcomes Measurement Information System (PROMIS) scores	PROMIS scores, Range 0 - 40, higher scores reflect worse quality	6 months
Secondary	Sleep related impairment: Patient-Reported Outcomes Measurement Information System (PROMIS) scores	PROMIS - impairment scores, range 0 - 40, higher scores reflect greater impairment	6 months
Secondary	Insomnia: Insomnia Severity Index (ISI)	ISI scores, Range 0 - 28; higher scores reflect higher insomnia burden/severity	6 months
Secondary	Epworth sleepiness scale	Epworth sleepiness scale scores, Range 0 - 24; higher scores signify greater sleepiness	6 months
Secondary	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
Secondary	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
Secondary	Attention	median reaction time and mean slowest 10% reaction time from a 5-min smartphone-based psychomotor vigilance test.	6 months