CompletedNCT01629823CPAPUpdated May 15, 2017Results posted

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

An interventional study of Continuous Positive Airway Pressure device (Resmed, Swift, Mirage) in Asthma, sponsored by American Lung Association Asthma Clinical Research Centers. Completed at 18 sites in United States. Open to participants aged 15 Years to 60 Years. Per ClinicalTrials.gov, last updated 2017-05-15.

Sponsored by American Lung Association Asthma Clinical Research Centers · Not applicable, Interventional, and Treatment

Phase: Not applicable
Study type: Interventional
Enrollment: 209
Allocation: Randomized
Ages: 15 Years to 60 Years
Sex: All

Study 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.

Read the 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).

Conditions studied

Asthma

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Asthma 3,920

In context

Asthma

3,920 studies on the registry are indexed under Asthma; 506 are open to participants now.

This study's enrollment of 209 is above the median of 83 across 2,751 interventional studies indexed under Asthma.

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Lead sponsor

American Lung Association Asthma Clinical Research Centers is the lead sponsor of 3 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 15 Years to 60 Years
Sexes eligible: All
Accepts healthy volunteers: No

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.

Study design

Phase: Not applicable
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: Triple (Participant, Care provider, Investigator)
Enrollment: 209 participants (actual)

Study arms

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

Interventions

DeviceContinuous 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.
Also known as: ResMed CPAP S9 series: Elite & Escape, Masks: Swift FX, Mirage FX

What researchers measure

Primary outcomes

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.
Time frame: 12 weeks after randomization

Results

Posted May 15, 2017

Participant flow

Trial Period

Participant flow — Trial Period
Milestone	CPAP Less Than 1 cm Water (H₂O)	CPAP 5cm H₂O	CPAP 10cm H₂O
Started	66	69	59
Completed	53	56	49
Not completed	13	13	10
Withdrew: Missed visit	11	9	8
Withdrew: Pre-diluent fev₁ predicted <70%	1	1	1
Withdrew: Pregnancy	1	0	0
Withdrew: Adverse event	0	1	0
Withdrew: Out-of-window visit	0	2	0
Withdrew: Failed to hold medication	0	0	1

Washout Period

Participant flow — Washout Period
Milestone	CPAP Less Than 1 cm Water (H₂O)	CPAP 5cm H₂O	CPAP 10cm H₂O
Started	54	57	50
Completed	51	51	50
Not completed	3	6	0
Withdrew: Safety	2	5	0
Withdrew: Pregnancy	1	0	0
Withdrew: Protocol violation	0	1	0

Outcome measures

PrimaryMethacholine 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.

Time frame:: 12 weeks after randomization
Reported as:: Geometric mean · mg/mL

Methacholine Reactivity
mg/mL	CPAP Less Than 1 cm H2O	CPAP 5cm H2O	CPAP 10cm H2O
PC20, 12-week	2.13 (1.30 to 3.49)	1.48 (0.96 to 2.28)	1.44 (0.91 to 2.27)
PC20, post-washout (14 weeks)	1.60 (0.96 to 2.69)	1.37 (0.91 to 2.07)	1.27 (0.81 to 2.01)

Statistical analysis

CPAP Less Than 1 cm H2O vs CPAP 5cm H2O · Regression, Linear · p = 0.51 (Comparison of 5cm group to control. No adjustment for multiple comparisons.) · Risk ratio (rr): 0.81 · 95% CI 0.44 to 1.50
CPAP Less Than 1 cm H2O vs CPAP 10cm H2O · Regression, Linear · p = 0.57 · Risk ratio (rr): 0.84 · 95% CI 0.47 to 1.52

Adverse events

Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
CPAP Less Than 1 cm H₂O	—	1/66 (1.5%)	34/58 (58.6%)
CPAP 5cm H₂O	—	1/69 (1.4%)	35/62 (56.5%)
CPAP 10cm H₂O	—	0/59 (0%)	25/57 (43.9%)

Most frequent serious events

Most frequent serious events
Event	CPAP Less Than 1 cm H₂O	CPAP 5cm H₂O	CPAP 10cm H₂O
Ischemic strokeNervous system disorders	1/66	0/69	0/59
PyleonephritisRenal and urinary disorders	1/66	0/69	0/59
Iron deficiency anemiaBlood and lymphatic system disorders	0/66	1/69	0/59

Most frequent other events

Most frequent other events
Event	CPAP Less Than 1 cm H₂O	CPAP 5cm H₂O	CPAP 10cm H₂O
Congestion, runny nose, sneezingGeneral disorders	21/52	25/52	14/46
HeadacheGeneral disorders	15/50	11/55	14/46
Drying of nose, mouth, and/or throatGeneral disorders	10/55	13/59	8/55
Acute upper respiratory tract infectionRespiratory, thoracic and mediastinal disorders	9/58	7/62	5/57
Nose irritationGeneral disorders	6/57	9/61	7/56
Ear or sinus discomfortEar and labyrinth disorders	7/57	8/60	6/56
Increased work breathingSocial circumstances	3/55	7/60	3/56
Eye irritationEye disorders	5/56	4/61	3/51

Baseline characteristics

Age, Continuous
Age, Continuous(years)	CPAP Less Than 1 cm H₂O	CPAP 5cm H₂O	CPAP 10cm H₂O	Total
Median	33 (23 to 47)	31 (20 to 40)	25 (18 to 39)	31 (20 to 41)

Sex: Female, Male
Sex: Female, Male(Participants)	CPAP Less Than 1 cm H₂O	CPAP 5cm H₂O	CPAP 10cm H₂O	Total
Female	42	35	36	113
Male	24	34	23	81

Region of Enrollment
Region of Enrollment(participants)	CPAP Less Than 1 cm H₂O	CPAP 5cm H₂O	CPAP 10cm H₂O	Total
United States	66	69	59	194

Asthma Symptom Utility Index (ASUI) Score
Asthma Symptom Utility Index (ASUI) Score(units on a scale)	CPAP Less Than 1 cm H₂O	CPAP 5cm H₂O	CPAP 10cm H₂O	Total
Median	0.89 (0.83 to 0.94)	0.94 (0.85 to 1.00)	0.92 (0.86 to 0.98)	0.92 (0.84 to 0.98)

Asthma Control Test (ACT) Score
Asthma Control Test (ACT) Score(units on a scale)	CPAP Less Than 1 cm H₂O	CPAP 5cm H₂O	CPAP 10cm H₂O	Total
Median	21 (19 to 23)	22 (20 to 24)	22 (20 to 23)	22 (20 to 23)

Marks Asthma Quality of Life
Marks Asthma Quality of Life(units on a scale)	CPAP Less Than 1 cm H₂O	CPAP 5cm H₂O	CPAP 10cm H₂O	Total
Median	9 (5 to 21)	7 (3 to 11)	6 (3 to 10)	7 (4 to 12)

Sinonasal Questionnaire (SNQ-6)
Sinonasal Questionnaire (SNQ-6)(units on a scale)	CPAP Less Than 1 cm H₂O	CPAP 5cm H₂O	CPAP 10cm H₂O	Total
Median	0.8 (0.6 to 1.6)	0.8 (0.4 to 1.4)	0.8 (0.4 to 1.2)	0.8 (0.4 to 1.4)

PC20
PC20(mg/mL)	CPAP Less Than 1 cm H₂O	CPAP 5cm H₂O	CPAP 10cm H₂O	Total
Median	1.06 (0.47 to 2.95)	0.96 (0.30 to 2.66)	0.89 (0.28 to 2.33)	0.98 (0.33 to 2.74)

8 further baseline measures are reported on the registry.

Study locations

18 sites

University of Arizona
Tucson, Arizona, United States
University of California, San Diego
San Diego, California, United States
National Jewish Health
Denver, Colorado, United States
Nemours Children's Clinic
Jacksonville, Florida, United States
University of Miami/ University of South Florida
Miami, Florida, United States
Illinois Consortium
Chicago, Illinois, United States
St. Vincent Hospital and Health Care Center, Inc
Indianapolis, Indiana 46260, 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
New York Medical College
Valhalla, New York, United States
Duke University Medical Center
Durham, North Carolina, United States
Ohio State University Medical Center/ Columbus Children's Hospital
Columbus, Ohio, United States
Baylor College of Medicine
Houston, Texas, United States
Northern New England Consortium
Colchester, Vermont, United States
University of Virginia
Charlottesville, Virginia, United States

References and documents

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. PubMed 27398992 ↗

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on May 15, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT01629823
Lead sponsor: American Lung Association Asthma Clinical Research Centers
Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
Responsible party: Robert A. Wise, M.D. (Robert A. Wise, M.D, American Lung Association Asthma Clinical Research Centers) — Principal investigator
First posted: Jun 28, 2012
Start date: Jul 2012
Primary completion: Oct 2014
Completion: Dec 2014
Results posted: May 15, 2017
Last update: May 15, 2017

Study contacts

Janet Holbrook, PHD

principal investigator · Johns Hopkins University

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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