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Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma (CPAP) (CPAP)

Primary Purpose

Asthma

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage)
Sponsored by
American Lung Association Asthma Clinical Research Centers
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Asthma

Eligibility Criteria

15 Years - 60 Years (Child, Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria

  • 15 - 60 years of age at V1
  • Physician diagnosis of asthma and on prescribed asthma medication for at least the past 12 months at V1
  • Pre-bronchodilator FEV₁ greater than or equal to 75% predicted at V1 (to minimize the likelihood that variability in FEV₁ will preclude participants from having methacholine challenges in follow-up visits)
  • Airways reactivity: Methacholine bronchial challenge with concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (PC ₂₀) less than or equal to 8 mg/mL at V1
  • Stable asthma defined by no change in treatment, emergency department (ED) visit, hospitalization, or urgent health care visit for asthma for the 8 weeks prior to screening
  • Non-smoker for more than 6 months and less than or equal to 10 pack-year history of smoking
  • Ability and willingness to provide informed consent
  • If receiving immunotherapy, must have had stable therapy for the 8 weeks prior to screening
  • Spend a minimum of six hours per night in bed on average
  • Willingness to sleep 5 days a week on average in the same place for the next 4 months
  • For women of child bearing potential; not pregnant, not lactating and agree to practice and adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study

Exclusion criteria

  • Weight less than or equal to 66 lbs. (30kg) at V1
  • BMI greater than or equal to 35 at V1
  • Acute respiratory illness in the month prior to screening
  • Systemic corticosteroid therapy during the 3 months preceding screening
  • History of sleep apnea by self-report High risk of sleep apnea as assessed by Multivariable Apnea Prediction (MAP) Index; high risk defined as probability that is equal to or greater than 20%
  • Chronic diseases (other than asthma) that in the opinion of the investigator would interfere with participation in the trial or put the participant at risk by participation, e.g. non-skin cancer, chronic diseases of the lung (other than asthma), chronic heart diseases, endocrine diseases, liver, kidney or nervous system diseases, or immunodeficiency, any pre-existing conditions that may be contraindications to positive airway pressure including: severe bullous lung disease, pneumothorax, pathologically low blood pressure, dehydration, cerebrospinal fluid leak, recent cranial surgery, trauma, bypassed upper (supraglottic) airway
  • Known sleep disorders that are currently under treatment by a sleep specialist
  • Known intolerance to methacholine
  • Absolute contraindications to methacholine that include: current use of beta-adrenergic blocking agent, heart attack or stroke in the last 3 months, uncontrolled hypertension, known aortic aneurysm
  • Use of investigative drugs or intervention trials in the 30 days prior to screening or during the duration of the study
  • Prior use of CPAP for any reason Homelessness, lack of telephone access, or intention to move within the next 4 months of the trial.
  • For blinding purposes, members from the same household cannot participate in the study at the same time.

Sites / Locations

  • University of Arizona
  • University of California, San Diego
  • National Jewish Health
  • Nemours Children's Clinic
  • University of Miami/ University of South Florida
  • Illinois Consortium
  • St. Vincent Hospital and Health Care Center, Inc
  • Louisiana State University Health Sciences Center, The Ernest N. Morial Asthma, Allergy and Respiratory Disease Center
  • University of Missouri, Kansas City School of Medicine
  • Washington University/ St. Louis University
  • Hofstra University School of Medicine
  • Columbia University - New York University Consortium
  • New York Medical College
  • Duke University Medical Center
  • Ohio State University Medical Center/ Columbus Children's Hospital
  • Baylor College of Medicine
  • Northern New England Consortium
  • University of Virginia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Sham Comparator

Experimental

Experimental

Arm Label

CPAP less than 1 cm H₂O

CPAP 10cm H₂O

CPAP 5cm H₂O

Arm Description

Outcomes

Primary Outcome Measures

Methacholine Reactivity
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

Full Information

First Posted
June 25, 2012
Last Updated
April 6, 2017
Sponsor
American Lung Association Asthma Clinical Research Centers
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)
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1. Study Identification

Unique Protocol Identification Number
NCT01629823
Brief Title
Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma (CPAP)
Acronym
CPAP
Official Title
Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma
Study Type
Interventional

2. Study Status

Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
July 2012 (Actual)
Primary Completion Date
October 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
American Lung Association Asthma Clinical Research Centers
Collaborators
National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Asthma

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigator
Allocation
Randomized
Enrollment
209 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CPAP less than 1 cm H₂O
Arm Type
Sham Comparator
Arm Title
CPAP 10cm H₂O
Arm Type
Experimental
Arm Title
CPAP 5cm H₂O
Arm Type
Experimental
Intervention Type
Device
Intervention Name(s)
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage)
Other Intervention Name(s)
ResMed CPAP S9 series: Elite & Escape, Masks: Swift FX, Mirage FX
Intervention Description
Continuous Positive Airway Pressure device (Resmed, Swift, Mirage): Participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm water (H₂O), 5 cm H₂O or 10 cm H₂O. They will be instructed to use the CPAP device every night for 12 weeks. Methacholine airways reactivity will be measured at the end of these 12 weeks and again after a 2-week washout period, 14 weeks after randomization.
Primary Outcome Measure Information:
Title
Methacholine Reactivity
Description
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.
Time Frame
12 weeks after randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion criteria 15 - 60 years of age at V1 Physician diagnosis of asthma and on prescribed asthma medication for at least the past 12 months at V1 Pre-bronchodilator FEV₁ greater than or equal to 75% predicted at V1 (to minimize the likelihood that variability in FEV₁ will preclude participants from having methacholine challenges in follow-up visits) Airways reactivity: Methacholine bronchial challenge with concentration of methacholine causing a 20% fall in forced expiratory volume in 1 second (PC ₂₀) less than or equal to 8 mg/mL at V1 Stable asthma defined by no change in treatment, emergency department (ED) visit, hospitalization, or urgent health care visit for asthma for the 8 weeks prior to screening Non-smoker for more than 6 months and less than or equal to 10 pack-year history of smoking Ability and willingness to provide informed consent If receiving immunotherapy, must have had stable therapy for the 8 weeks prior to screening Spend a minimum of six hours per night in bed on average Willingness to sleep 5 days a week on average in the same place for the next 4 months For women of child bearing potential; not pregnant, not lactating and agree to practice and adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study Exclusion criteria Weight less than or equal to 66 lbs. (30kg) at V1 BMI greater than or equal to 35 at V1 Acute respiratory illness in the month prior to screening Systemic corticosteroid therapy during the 3 months preceding screening History of sleep apnea by self-report High risk of sleep apnea as assessed by Multivariable Apnea Prediction (MAP) Index; high risk defined as probability that is equal to or greater than 20% Chronic diseases (other than asthma) that in the opinion of the investigator would interfere with participation in the trial or put the participant at risk by participation, e.g. non-skin cancer, chronic diseases of the lung (other than asthma), chronic heart diseases, endocrine diseases, liver, kidney or nervous system diseases, or immunodeficiency, any pre-existing conditions that may be contraindications to positive airway pressure including: severe bullous lung disease, pneumothorax, pathologically low blood pressure, dehydration, cerebrospinal fluid leak, recent cranial surgery, trauma, bypassed upper (supraglottic) airway Known sleep disorders that are currently under treatment by a sleep specialist Known intolerance to methacholine Absolute contraindications to methacholine that include: current use of beta-adrenergic blocking agent, heart attack or stroke in the last 3 months, uncontrolled hypertension, known aortic aneurysm Use of investigative drugs or intervention trials in the 30 days prior to screening or during the duration of the study Prior use of CPAP for any reason Homelessness, lack of telephone access, or intention to move within the next 4 months of the trial. For blinding purposes, members from the same household cannot participate in the study at the same time.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Janet Holbrook, PHD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Arizona
City
Tucson
State/Province
Arizona
Country
United States
Facility Name
University of California, San Diego
City
San Diego
State/Province
California
Country
United States
Facility Name
National Jewish Health
City
Denver
State/Province
Colorado
Country
United States
Facility Name
Nemours Children's Clinic
City
Jacksonville
State/Province
Florida
Country
United States
Facility Name
University of Miami/ University of South Florida
City
Miami
State/Province
Florida
Country
United States
Facility Name
Illinois Consortium
City
Chicago
State/Province
Illinois
Country
United States
Facility Name
St. Vincent Hospital and Health Care Center, Inc
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46260
Country
United States
Facility Name
Louisiana State University Health Sciences Center, The Ernest N. Morial Asthma, Allergy and Respiratory Disease Center
City
New Orleans
State/Province
Louisiana
Country
United States
Facility Name
University of Missouri, Kansas City School of Medicine
City
Kansas City
State/Province
Missouri
Country
United States
Facility Name
Washington University/ St. Louis University
City
St Louis
State/Province
Missouri
Country
United States
Facility Name
Hofstra University School of Medicine
City
Hempstead
State/Province
New York
Country
United States
Facility Name
Columbia University - New York University Consortium
City
New York
State/Province
New York
Country
United States
Facility Name
New York Medical College
City
Valhalla
State/Province
New York
Country
United States
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
Country
United States
Facility Name
Ohio State University Medical Center/ Columbus Children's Hospital
City
Columbus
State/Province
Ohio
Country
United States
Facility Name
Baylor College of Medicine
City
Houston
State/Province
Texas
Country
United States
Facility Name
Northern New England Consortium
City
Colchester
State/Province
Vermont
Country
United States
Facility Name
University of Virginia
City
Charlottesville
State/Province
Virginia
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
27398992
Citation
Holbrook JT, Sugar EA, Brown RH, Drye LT, Irvin CG, Schwartz AR, Tepper RS, Wise RA, Yasin RZ, Busk MF; American Lung Association Airways Clinical Research Centers. Effect of Continuous Positive Airway Pressure on Airway Reactivity in Asthma. A Randomized, Sham-controlled Clinical Trial. Ann Am Thorac Soc. 2016 Nov;13(11):1940-1950. doi: 10.1513/AnnalsATS.201601-043OC.
Results Reference
derived

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Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma (CPAP)

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