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

• ClinicalTrials.gov Identifier: NCT01629823
• Recruitment Status: Completed
• First Posted: June 28, 2012
• Results First Posted: May 15, 2017
• Last Update Posted: May 15, 2017
• Sponsor: American Lung Association Asthma Clinical Research Centers
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI)
• Information provided by (Responsible Party): Robert A. Wise, M.D., American Lung Association Asthma Clinical Research Centers

Tracking Information

• First Submitted Date: June 25, 2012
• First Posted Date: June 28, 2012
• Results First Submitted Date: January 30, 2017
• Results First Posted Date: May 15, 2017
• Last Update Posted Date: May 15, 2017
• Actual Study Start Date: July 2012
• Actual Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 6, 2017)

Methacholine Reactivity [ Time Frame: 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.

Original Primary Outcome Measures (submitted: June 26, 2012)

Methacholine reactivity [ Time Frame: 16 weeks ]

Airways reactivity will be measured with methacholine challenge testing, following ATS guidelines using the dosimeter technique .

• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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
• 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).

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Treatment
• Condition: Asthma

Intervention

Device: Continuous Positive Airway Pressure device (Resmed, Swift, Mirage)

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.

Other Names:

• ResMed CPAP S9 series: Elite & Escape
• Masks: Swift FX, Mirage FX

Study Arms

• Sham Comparator: CPAP less than 1 cm H₂O
  Intervention: Device: Continuous Positive Airway Pressure device (Resmed, Swift, Mirage)
• Experimental: CPAP 10cm H₂O
  Intervention: Device: Continuous Positive Airway Pressure device (Resmed, Swift, Mirage)
• Experimental: CPAP 5cm H₂O
  Intervention: Device: Continuous Positive Airway Pressure device (Resmed, Swift, Mirage)

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 6, 2017): 209
• Original Estimated Enrollment (submitted: June 26, 2012): 192
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 15 Years to 60 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01629823
• Other Study ID Numbers: ALA-ACRC-13; U01HL108730 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Robert A. Wise, M.D., American Lung Association Asthma Clinical Research Centers
• Original Responsible Party: American Lung Association Asthma Clinical Research Centers
• Current Study Sponsor: American Lung Association Asthma Clinical Research Centers
• Original Study Sponsor: Same as current
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Principal Investigator: Janet Holbrook, PHD; Johns Hopkins University

• PRS Account: American Lung Association Asthma Clinical Research Centers
• Verification Date: April 2017