Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma (CPAP)
- Conditions
- Asthma
- Interventions
- Device: Continuous Positive Airway Pressure device (Resmed, Swift, Mirage)
- Registration Number
- NCT01629823
- Lead Sponsor
- American Lung Association Asthma Clinical Research Centers
- Brief Summary
The CPAP trial is a 3-arm parallel design randomized sham-controlled trial. Participants are randomly assigned in equal allocation to one of three treatments: CPAP 10 cm water (H₂O) (high) vs. CPAP 5 cm H₂O (medium) vs. CPAP Sham (less than 1 cm H₂O, Low). The treatment period is 12 weeks with airways reactivity assessed at baseline, 6 and 12 weeks of treatment and after a 2 week washout.
- Detailed Description
It is now well established that failure to rhythmically apply strain to airway smooth muscle leads to change in the biomechanics of the smooth muscle characterized by shortened resting length and increased sensitivity to pharmacologic constrictors. Patients with asthma have physiologic airway characteristics that recapitulate this condition - increased airway tone and increased sensitivity to methacholine. It is our underlying hypothesis that asthma, although it may be initiated by allergic airway inflammation, is promoted by decreased tidal force fluctuations during recumbent sleep. If this is true, then treatments that increase tidal force fluctuations of airways should reverse these abnormalities. One treatment that increases tidal force fluctuations is continuous positive airway pressure (CPAP). CPAP prevents a fall in end expiratory lung volume and prevents closure of airways in dependent regions of the lung thereby permitting the stresses of tidal breathing to apply strain to airways. Preliminary data in 15 asthmatics showed that 1 week of 10cm H₂O nocturnal CPAP was associated with a remarkable 2.7-fold increase in the concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (FEV₁) (PC20). The objective of this study is to conduct a randomized, sham-controlled, multicenter study of 5 and 10 cm H₂O CPAP in order to verify these findings; to assess the effect of nocturnal CPAP on airways reactivity; to determine the durability of the effect over 12 weeks; to assess the safety, tolerability and adherence to this treatment; and to explore if there are clinically meaningful benefits. The study will be conducted at 18 centers of the American Lung Association-Asthma Clinical Research Centers (ALA-ACRC) with the Data Coordinating Center (DCC) at Johns Hopkins University.
A substudy of High Resolution Computed Tomography (HRCT) will also be conducted at a subset of the ACRC clinics. A total of 54 subjects (18 per arm)who are randomized in the main study will be voluntarily enrolled in the substudy to compare the structural changes in the airways across treatment groups and to correlate structural changes with the physiological changes. A total of two visits will be conducted. HRCT Visit 1 will be performed after randomization in the main CPAP study, and prior to initiation of CPAP. HRCT Visit 2 will be performed between weeks 10 and 12 of CPAP, at a different day or prior of methacholine challenge testing.Two CT scans will be performed each at different lung volume at each visit (Total of 4 scans for the study duration). The first volume will be at Total Lung Capacity (TLC), followed by another CT scan at Functional Residual Capacity (FRC).
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 209
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description CPAP less than 1 cm H₂O Continuous Positive Airway Pressure device (Resmed, Swift, Mirage) - CPAP 10cm H₂O Continuous Positive Airway Pressure device (Resmed, Swift, Mirage) - CPAP 5cm H₂O Continuous Positive Airway Pressure device (Resmed, Swift, Mirage) -
- Primary Outcome Measures
Name Time Method Methacholine Reactivity 12 weeks after randomization The primary outcome measure was the change in provocative concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (FEV₁) (PC20) from baseline to 12 weeks. Modified American Thoracic Society guidelines were followed for pre-bronchodilator spirometry and methacholine challenge testing using the 5 breath dosimeter technique. Up to eleven doses, each a doubling concentration of methacholine (Provocholine™), were inhaled starting at 0.03 mg/mL until a 20% or greater fall in FEV₁ occurred; the maximum dose was 32 mg/mL. Breaths each of doubling concentrations of methacholine were inhaled from a calibrated DeVilbiss™ 646 nebulizer.
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (18)
St. Vincent Hospital and Health Care Center, Inc
🇺🇸Indianapolis, Indiana, United States
New York Medical College
🇺🇸Valhalla, New York, United States
Ohio State University Medical Center/ Columbus Children's Hospital
🇺🇸Columbus, Ohio, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Arizona
🇺🇸Tucson, Arizona, United States
University of Virginia
🇺🇸Charlottesville, Virginia, United States
Northern New England Consortium
🇺🇸Colchester, Vermont, United States
Nemours Children's Clinic
🇺🇸Jacksonville, Florida, United States
University of California, San Diego
🇺🇸San Diego, California, United States
National Jewish Health
🇺🇸Denver, Colorado, United States
Illinois Consortium
🇺🇸Chicago, Illinois, United States
University of Miami/ University of South Florida
🇺🇸Miami, Florida, United States
Louisiana State University Health Sciences Center, The Ernest N. Morial Asthma, Allergy and Respiratory Disease Center
🇺🇸New Orleans, Louisiana, United States
University of Missouri, Kansas City School of Medicine
🇺🇸Kansas City, Missouri, United States
Washington University/ St. Louis University
🇺🇸St Louis, Missouri, United States
Hofstra University School of Medicine
🇺🇸Hempstead, New York, United States
Columbia University - New York University Consortium
🇺🇸New York, New York, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States