Effect of CPAP on Abnormal Gastroesophageal Reflux and Lung Inflammation in IPF

Sponsor

University of Arizona (Other)

Overall Status

Recruiting

CT.gov ID

NCT05359965

Collaborator

Boehringer Ingelheim (Industry)

Enrollment

Location

Arms

Anticipated Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the effect of CPAP therapy on esophageal pH and lung inflammation in patients with idiopathic pulmonary fibrosis (IPF) and sleep apnea.

Condition or Disease	Intervention/Treatment	Phase
Idiopathic Pulmonary Fibrosis Obstructive Sleep Apnea Gastro Esophageal Reflux	Device: Positive Airway Pressure	N/A

Detailed Description

Participants in this study will have an overnight sleep study done while wearing a 24 hour pH monitor in the esophagus. If the participant has sleep apnea, he or she will be randomly assigned to receive either CPAP treatment or no CPAP treatment. After 4 weeks, the participant will have another overnight sleep study with 24 hour pH monitoring. Blood will also be collected at both time points and again after 6 months to measure biomarkers that are related to lung inflammation.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Subjects will be assigned to treatment groups using a 1:1 randomized block design via the randomization module in REDCap. The PI and study coordinator will be blinded to next assignment.Subjects will be assigned to treatment groups using a 1:1 randomized block design via the randomization module in REDCap. The PI and study coordinator will be blinded to next assignment.

Masking:

Triple (Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Study investigators and care providers will be blinded and not involved in any CPAP or no CPAP related set-up, instruction, or device troubleshooting during the course the treatment phase. Lab personnel performing biomarker analysis will only have access to subject study ID and not treatment group assignments.

Primary Purpose:

Treatment

Official Title:

Effect of Continuous Positive Airway Pressure (CPAP) on Abnormal Gastroesophageal Reflux and Lung Inflammation in Idiopathic Pulmonary Fibrosis (IPF)

Actual Study Start Date :

Oct 1, 2019

Anticipated Primary Completion Date :

Dec 1, 2022

Anticipated Study Completion Date :

Mar 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CPAP Subjects randomized to the treatment arm, will receive continuous positive airway pressure (CPAP) while sleeping via an autoPAP device for 4 weeks.	Device: Positive Airway Pressure Gentle and steady pressure (with or without supplemental oxygen) delivered to the airways of the lungs while subjects are sleeping.
No Intervention: No CPAP Subjects assigned to the no CPAP group will not have any intervention for a 4 week period.

Arm

Intervention/Treatment

Experimental: CPAP

Subjects randomized to the treatment arm, will receive continuous positive airway pressure (CPAP) while sleeping via an autoPAP device for 4 weeks.

Device: Positive Airway Pressure

Gentle and steady pressure (with or without supplemental oxygen) delivered to the airways of the lungs while subjects are sleeping.

No Intervention: No CPAP

Subjects assigned to the no CPAP group will not have any intervention for a 4 week period.

Outcome Measures

Primary Outcome Measures

Composite Biomarker Score [4 weeks]
The primary outcome will be a composite value that is a weighted average of z-scores of the biomarkers MMP1, MMP7, IL-8, KL-6, and CXCL13, weighted by the univariate effect sizes of each biomarker. MMP1, MMP7, IL-8, KL-6, and CXCL13 will be measured using enzyme linked immunosorbent assays (ELISA) for these analytes. (Z-score is a unitless number, as is the weighted average.)

Secondary Outcome Measures

Biomarker of Lung Inflammation: KL-6 [4 weeks]
The value of KL-6 measured by ELISA in U/ml.
Biomarker of Lung Inflammation: MMP1 [4 weeks]
The value of MMP1 measured by ELISA in ng/ml.
Biomarker of Lung Inflammation: MMP7 [4 weeks]
The value of MMP7 measured by ELISA in ng/ml.
Biomarker of Lung Inflammation: IL-8 [4 weeks]
The value of IL-8 measured by ELISA in pg/ml.
Biomarker of Lung Inflammation: CXCL13 [4 weeks]
The value of CXCL-13 measured by ELISA in pg/ml.
Esophageal pH During Sleep [4 weeks]
Total sleep time (in minutes) with pH less than 4.
24hr-Esophageal pH [4 weeks]
Total time (minutes in 24hr period) with pH less than 4.
FVC change [6 months]
FVC change in percentage of predicted values over 6 months (baseline to 6 months).
Composite Biomarker Score at Six Months [6 months]
Weighted average of z-scores of the biomarkers MMP1, MMP7, IL8, KL-6, and CXCL13, weighted by the univariate effect sizes of each biomarker at six months. (Z-score is a unitless number, as is the weighted average.)

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

confirmed diagnosis of IPF based on the 2018 IPF guidelines
high likelihood of OSA based on the STOP-BANG measure, with a score of 3 or greater
patients on nintedanib, or in whom nintedanib will be initiated prior to enrollment in the study
able to participated in 24hr pH monitoring
able to comply with CPAP treatment
able to provide written informed consent prior to any study procedures
willing to complete all study measurements and assessments in compliance with the protocol

Exclusion Criteria:

interstitial lung disease caused by conditions other than IPF
severe concomitant illness limiting life expectancy (< 1 year)
residual lung volume > or equal to 120% of predicted
obstructive lung disease: FEV1/FVC ratio < 0.70
current drug or alcohol dependence
patients who are unable to tolerate nintedanib
patients who are unable to use CPAP or are unwilling to participate in the 24 hr pH probe placement
patients who were diagnosed with recent IPF exacerbation within 4 weeks of enrollment (may be rescheduled for enrollment once recovered)