Clinical trial NCT01629823: Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma (CPAP)
Official title: Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Lead sponsor: American Lung Association Asthma Clinical Research Centers
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2012-06-28
Enrollment: 209
Sex: ALL
Minimum age (years): 15
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Primary outcomes:
measure: Methacholine Reactivity
timeFrame: 12 weeks after randomization
Secondary outcomes:
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: San Diego
country: United States
facility: University of California, San Diego
state: California
city: Denver
country: United States
facility: National Jewish Health
state: Colorado
city: Jacksonville
country: United States
facility: Nemours Children's Clinic
state: Florida
city: Miami
country: United States
facility: University of Miami/ University of South Florida
state: Florida
city: Chicago
country: United States
facility: Illinois Consortium
state: Illinois
city: Indianapolis
country: United States
facility: St. Vincent Hospital and Health Care Center, Inc
state: Indiana
city: New Orleans
country: United States
facility: Louisiana State University Health Sciences Center, The Ernest N. Morial Asthma, Allergy and Respiratory Disease Center
state: Louisiana
city: Kansas City
country: United States
facility: University of Missouri, Kansas City School of Medicine
state: Missouri
city: St Louis
country: United States
facility: Washington University/ St. Louis University
state: Missouri
city: Hempstead
country: United States
facility: Hofstra University School of Medicine
state: New York
city: New York
country: United States
facility: Columbia University - New York University Consortium
state: New York
city: Valhalla
country: United States
facility: New York Medical College
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Medical Center/ Columbus Children's Hospital
state: Ohio
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: Colchester
country: United States
facility: Northern New England Consortium
state: Vermont
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
Study officials:
affiliation: Johns Hopkins University
name: Janet Holbrook, PHD
role: PRINCIPAL_INVESTIGATOR
References:
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.