Assessment of Continuous Positive Airway Pressure Therapy in IPF

Study Overview
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Brief Summary
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The purpose of this study is to evaluate whether biomarkers of lung injury and remodeling are responsive to effective continuous positive airway pressure (CPAP) treatment in adults with idiopathic pulmonary fibrosis (IPF) and moderate-to-severe obstructive sleep apnea (OSA).

Detailed Description
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Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease of the peripheral lung parenchyma that affects 0.5% of older adults in the U.S. and confers a very poor median survival. Repetitive injury to the lung with abnormal healing likely results in fibrosis as treatment of those risk factors that cause these injuries may improve outcomes. Obstructive sleep apnea (OSA), a form of sleep disordered breathing, is highly prevalent in adults with IPF and may be a risk factor in IPF by exerting peripheral tractional stress on the lung and promoting oxidative injury by intermittent hypoxia. Effective treatment of OSA with continuous positive airway pressure (CPAP) reduces the number of obstructive events in OSA and therefore may reduce repetitive injury to the lung in adults with IPF. Participants in this study will undergo polysomnography to determine whether they have OSA, and if so, its severity based on the apnea-hypopnea index (AHI, events/ hour). Those participants with moderate-to-severe OSA will undergo CPAP treatment for up to 48 weeks with an interim period of withdrawal of CPAP. The primary aim of this study will examine the effect of CPAP treatment and its withdrawal and re-initiation on biomarkers of lung injury and remodeling in adults with IPF and moderate-to-severe OSA who are adherent to CPAP (expected sample size for this group is 30). The study will stop enrollment after 30 participants in this group are enrolled.

Official Title
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Assessment of Continuous Positive Airway Pressure Therapy in IPF

Conditions
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Interstitial Lung Disease, Obstructive Sleep Apnea

Intervention / Treatment
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* Device: Auto-CPAP
* Other: Withdrawal of Auto-CPAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent Age equal to or greater than 50 years Diagnosis of IPF as defined by the 2018 ATS/ERS/JRS/ALAT guidelines Exclusion Criteria: Clinically significant lung disease other than IPF Planned change to the IPF treatment during the study period Known contraindication to CPAP Current use of CPAP, an oral appliance, or hypoglossal nerve stimulation for treatment of OSA Current cigarette smoking (past 4 weeks) Lower respiratory tract infection in the past 60 days. (Upper respiratory tract infection is not a contraindication) History of life-threatening cardiac arrhythmias Known chronic heart failure (Left ventricle ejection fraction < 45% or echo evidence of right ventricle dysfunction or pulmonary hypertension) Chronic opiate analgesic use History of stroke or spinal cord injury History of sleepiness-related automobile accident within past year of enrollment Expected survival time in the opinion of the investigator of less than 6 months Commercial driver's license or occupation

Ages Eligible for Study
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Minimum Age: 50 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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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Interventional Model Description: Participants with moderate-to-severe OSA will be treated for 12 weeks with Auto-CPAP followed by withdrawal of auto-CPAP
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Moderate to Severe OSA - treated<br>Moderate-to-severe OSA Treated with and adherent to Auto-CPAP | Device: Auto-CPAP<br>* Use of Auto-CPAP<br>|
| Experimental: Moderate to Severe OSA - withdrawal<br>Moderate-to-severe OSA Withdrawal of Auto-CPAP | Other: Withdrawal of Auto-CPAP<br>* Withdrawal of Auto-CPAP<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum matrix metalloproteinase-7 (MMP-7, ng/mL) | The differences between-arm difference in the longitudinal changes of MMP-7 will be measured. | Up to 24 Weeks | 
| Serum surfactant protein-D (SP-D, ng/mL) | The between-arm difference in the longitudinal changes of SP-D will be measured. | Up to 24 Weeks | 
| Serum Angiopoietin-2 (Ang-2, ng/mL) | The between-arm difference in the longitudinal changes of Ang-2 will be measured. | Up to 48 Weeks | 
| Serum surfactant protein-A (SP-A, ng/mL) | The between-arm difference in the longitudinal changes of SP-A will be measured. | Up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced vital capacity (FVC) | Forced vital capacity, or FVC, is defined as the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible. | 24 and 48 weeks | 
| Diffusing capacity of the lung for carbon monoxide (DLCO) | Diffusing capacity of the lungs for carbon monoxide (DLCO) is a medical test that determines how much oxygen travels from the alveoli of the lungs to the blood stream. | 24 and 48 weeks | 
| Score on St. George's Respiratory Questionnaire (SGRQ) | The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in patients with diseases of airways obstruction. Scores range from 0 to 100, with higher scores indicating more limitations. | 24 and 48 weeks | 
| Score on University of California San Diego (USCD) Shortness of Breath Questionnaire (SOBQ) | The SOBQ is a a 24-item questionnaire that assesses self-reported shortness of breath while performing a variety of activities of daily living. Items are assessed on a 6-point scale (0 = not at all to 5 = maximal or unable to do because of breathlessness) for a total score ranging from 0 to 120. | 24 and 48 weeks | 
| Score on Epworth Sleepiness Scale (ESS) | The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'. | 24 and 48 weeks | 
| Sleep Apnea Quality of Life Index (SAQLI) | The SAQLI is a 35-item questionnaire is used to assess obstructive sleep apnea-related quality of life (QOL). Items are assessed on a 7-point scale with 0 indicating all the time to 7 indicating not at all. | 24 and 48 weeks | 
| Assess Quality of life in Idiopathic Pulmonary Fibrosis (ATAQ-IPF) | ATAQ-IPF is a 74-item questionnaire used to assess quality of life among adults with idiopathic pulmonary fibrosis. | 24 and 48 weeks | 
| Gastroesophageal Reflux Disease Questionnaire (GERD-Q) | GerdQ is a 6-item questionnaire to assess gastroesophageal reflux symptoms. | 24 and 48 weeks | 
| Cough Visual Analog Scale | Cough visual analog scale, a standardized scale ranging from 0 (no cough) to 100 (severe cough) on a continuous scale. | 24 and 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Interstitial Lung Disease (ILD), Idiopathic Pulmonary Fibrosis (IPF), Obstructive Sleep Apnea (OSA), CPAP