Clinical trial NCT03901534: Assessment of Continuous Positive Airway Pressure Therapy in OSA and ILD
Official title: Assessment of Continuous Positive Airway Pressure Therapy in OSA and ILD
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Interstitial Lung Disease
Obstructive Sleep Apnea
Keywords: Interstitial Lung Disease (ILD)
Obstructive Sleep Apnea (OSA)
CPAP
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2019-04-03
Enrollment: 2021
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate whether biomarkers of lung epithelial and endothelial injury are associated with obstructive sleep apnea (OSA) and interstitial lung disease (ILD).

Detailed description: This study is comprised of 3 aims:

Aim 1: Determine whether the greater OSA severity is associated with higher levels of serum biomarkers of AEC and endothelial injury and ECM remodeling in community-dwelling adults. This is a retrospective study that will analyze biospecimens from those who participated in the MESA sleep study \[Chen et al\].

Aim 2: Determine whether CPAP use is associated with reductions in alveolar epithelial cell (AEC) injury and endothelial injury, and extracellular matrix (ECM) remodeling biomarkers in adults with moderate-to-severe OSA. This is a retrospective study that will analyze biospecimens from those who participated in either the HeartBEAT \[Gottlieb et al\] and BestAIR \[Bakker et al\] studies.

Revised Aim 3: a) Determine whether untreated OSA promotes AEC and endothelial injury and ECM remodeling biomarkers in adults with ILD and OSA compared with those without OSA; b) Determine prospectively whether clinically-initiated 4-week PAP therapy increases markers of alveolar endothelial lung injury in OSA. Participants will be recruited at Columbia University and be assigned CPAP therapy as an intervention.

Eligibility criteria: Inclusion Criteria for Patients with ILD:

1. Ability to provide informed consent.
2. Age 18 years or greater
3. Diagnosis of any of the following fibrotic interstitial lung diseases as defined by ATS/ERS/JRS/ALAT guidelines and research statements and Delphi surveys:

   * Idiopathic pulmonary fibrosis
   * Idiopathic non-specific interstitial pneumonia (NSIP) with fibrosis
   * Chronic hypersensitivity pneumonitis with fibrosis
   * Connective tissue disease related interstitial lung disease (CTD-ILD)
   * Unclassifiable idiopathic interstitial pneumonia with fibrosis

Exclusion criteria for Patients with ILD:

1. Clinically significant lung disease other than fibrotic interstitial lung disease
2. Planned change to the IPF treatment during the study period
3. Current cigarette smoking (past 4 weeks)
4. Lower respiratory tract infection in past 60 days. (Upper respiratory tract infection is not a contraindication)
5. History of life-threatening cardiac arrhythmias
6. Known chronic heart failure (LVEF \< 45% or echo evidence of RV dysfunction or PH)
7. Chronic opiate analgesic use
8. History of sleepiness-related automobile accident within past year of enrollment
9. Expected survival time in the opinion of the investigator of less than 6 months
10. History of stroke or spinal cord injury

Inclusion criteria for OSA patients:

1. Age 18 years or greater
2. Clinical diagnosis of untreated OSA documented by nocturnal polysomnography

Exclusion criteria for OSA patients:

1. Current treatment with CPAP or oral appliance
2. Identical exclusion criteria as for ILD patients

Primary outcomes:
measure: Surfactant Protein D (SP-D) [Aim 1]
timeFrame: 1 day
measure: E-selectin [Aim 1]
timeFrame: 1 day
measure: Angiopoietin-2 [Aim 1]
timeFrame: 1 day
measure: Vascular Endothelial Growth Factor-A (VEGF-A) [Aim 1]
timeFrame: 1 day
measure: Angiopoietin-interacting Soluble Tie-2 (sTie2) [Aim 1]
timeFrame: 1 day
measure: Change in Serum Matrix Metalloproteinase-7 (MMP-7) Following CPAP [Aim 2]
timeFrame: Baseline and post-CPAP follow-up, up to 24 Weeks
measure: Change in Serum Surfactant Protein-D (SP-D) Following CPAP [Aim 2]
timeFrame: Baseline and post-CPAP follow-up, up to 24 Weeks
measure: Change in Serum Angiopoietin-2 (Ang-2) Following CPAP [Aim 2]
timeFrame: Baseline and post-CPAP follow-up, up to 24 Weeks
measure: Change in Serum Osteopontin Following CPAP [Aim 2]
timeFrame: Baseline and post-CPAP follow-up, up to 24 Weeks
measure: Serum Angiopoietin-2 (Ang-2, ng/mL) [Aim 3a]
timeFrame: Baseline and 4 weeks
Secondary outcomes:
Other outcomes:
measure: Serum Surfactant Protein-A (SP-A, ng/mL)
timeFrame: Up to 24 weeks
Locations:
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
Study officials:
References:
citation: Chen X, Wang R, Zee P, Lutsey PL, Javaheri S, Alcantara C, Jackson CL, Williams MA, Redline S. Racial/Ethnic Differences in Sleep Disturbances: The Multi-Ethnic Study of Atherosclerosis (MESA). Sleep. 2015 Jun 1;38(6):877-88. doi: 10.5665/sleep.4732.
citation: Gottlieb DJ, Punjabi NM, Mehra R, Patel SR, Quan SF, Babineau DC, Tracy RP, Rueschman M, Blumenthal RS, Lewis EF, Bhatt DL, Redline S. CPAP versus oxygen in obstructive sleep apnea. N Engl J Med. 2014 Jun 12;370(24):2276-85. doi: 10.1056/NEJMoa1306766.
citation: Bakker JP, Wang R, Weng J, Aloia MS, Toth C, Morrical MG, Gleason KJ, Rueschman M, Dorsey C, Patel SR, Ware JH, Mittleman MA, Redline S. Motivational Enhancement for Increasing Adherence to CPAP: A Randomized Controlled Trial. Chest. 2016 Aug;150(2):337-45. doi: 10.1016/j.chest.2016.03.019. Epub 2016 Mar 24.