Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma (CPAP)
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Purpose
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 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.
| Condition | Intervention | Phase |
|---|---|---|
|
Asthma |
Device: Continuous Positive Airway Pressure device (Resmed, Swift, Mirage) |
Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment |
| Official Title: | Effect of Positive Airway Pressure on Reducing Airway Reactivity in Patients With Asthma |
- Methacholine reactivity [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]Airways reactivity will be measured with methacholine challenge testing, following ATS guidelines using the dosimeter technique .
| Estimated Enrollment: | 192 |
| Study Start Date: | July 2012 |
| Estimated Primary Completion Date: | June 2014 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| Sham Comparator: CPAP less than 1 cm H2O |
Device: Continuous Positive Airway Pressure device (Resmed, Swift, Mirage)
participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm H2O, 5H2O or 10H2O. they will be instructed to use the CPAP device every night for 12 weeks. There will be a washout methacholine measurement after a 2 week washout period.
Other Names:
|
| Experimental: CPAP 10cm H2O |
Device: Continuous Positive Airway Pressure device (Resmed, Swift, Mirage)
participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm H2O, 5H2O or 10H2O. they will be instructed to use the CPAP device every night for 12 weeks. There will be a washout methacholine measurement after a 2 week washout period.
Other Names:
|
| Experimental: CPAP 5cm H2O |
Device: Continuous Positive Airway Pressure device (Resmed, Swift, Mirage)
participants will be randomized to one of three pre-set CPAP pressures: less than 1 cm H2O, 5H2O or 10H2O. they will be instructed to use the CPAP device every night for 12 weeks. There will be a washout methacholine measurement after a 2 week washout period.
Other Names:
|
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 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 48 subjects (16 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| Ages Eligible for Study: | 15 Years to 60 Years |
| Genders Eligible for Study: | Both |
| 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 PC₂₀ less than or equal 8 mg/mL for FEV₁ at V1
- Stable asthma defined by no change in treatment, 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.
Contacts and Locations| Contact: Razan Yasin, MHS | 443‐287‐5796 | ryasin@jhsph.edu |
| United States, Arizona | |
| University of Arizona | Recruiting |
| Tucson, Arizona, United States | |
| Contact: Monica Vasquez 520-626-3907 mvasquez@arc.arizona.edu | |
| Principal Investigator: Lynn Gerald, PhD, MSPH | |
| United States, California | |
| University of California, San Diego | Recruiting |
| San Diego, California, United States | |
| Contact: Katie Kinninger 619-471-0820 kkinninger@ucsd.edu | |
| Principal Investigator: Stephen Wasserman, MD | |
| United States, Colorado | |
| National Jewish Health | Recruiting |
| Denver, Colorado, United States | |
| Contact: Trisha Larson 303-270-1220 larsont@njhealth.org | |
| Principal Investigator: Rohit Katial | |
| United States, Florida | |
| Nemours Children's Clinic | Recruiting |
| Jacksonville, Florida, United States | |
| Contact: Mary Warde 904-697-3176 mwarde@nemours.org | |
| Principal Investigator: John Lima, PharmD | |
| University of Miami/ University of South Florida | Recruiting |
| Miami, Florida, United States | |
| Contact: Eliana Mendes 305-243-2568 emendes@med.miami.edu | |
| Principal Investigator: Adam Wanner, MD | |
| United States, Illinois | |
| Illinois Consortium | Recruiting |
| Chicago, Illinois, United States | |
| Contact: Jenny Hixon 312-926-0975 j-franzen@northwestern.edu | |
| Principal Investigator: Lewis Smith, MD | |
| United States, Indiana | |
| St. Vincent Hospital and Health Care Center, Inc | Not yet recruiting |
| Indianapolis, Indiana, United States, 46260 | |
| Contact: Michael Busk, MD, MPH | |
| Principal Investigator: Michael Busk, MD, MPH | |
| United States, Louisiana | |
| Louisiana State University Health Sciences Center, The Ernest N. Morial Asthma, Allergy and Respiratory Disease Center | Recruiting |
| New Orleans, Louisiana, United States | |
| Contact: Marie Sandi 504-568-3450 mchild@lsuhsc.edu | |
| Principal Investigator: Kyle Happel, MD | |
| United States, Missouri | |
| University of Missouri, Kansas City School of Medicine | Recruiting |
| Kansas City, Missouri, United States | |
| Contact: Patti Haney 816-404-5503 patti.haney@tmcmed.org | |
| Principal Investigator: Gary Salzman, MD | |
| Washington University/ St. Louis University | Recruiting |
| St Louis, Missouri, United States | |
| Contact: Jaime Tarsi 314-747-3074 jtarsi@dom.wustl.edu | |
| Principal Investigator: Mario Castro, MD, MPH | |
| United States, New York | |
| Hofstra University School of Medicine | Recruiting |
| Hempstead, New York, United States | |
| Contact: Ramona Ramdeo 516-465-5461 rramdeo@lij.edu | |
| Principal Investigator: Rubin Cohen, MD | |
| Columbia University - New York University Consortium | Not yet recruiting |
| New York, New York, United States | |
| Contact: Karen Carapetyan 212-263-2252 carapk01@nyumc.org | |
| Principal Investigator: Joan Reibman, MD | |
| New York Medical College | Recruiting |
| Valhalla, New York, United States | |
| Contact: Ingrid Gherson 914-594-3320 ingrid_gherson@nymc.edu | |
| Principal Investigator: Allen Dozor, MD | |
| United States, North Carolina | |
| Duke University Medical Center | Recruiting |
| Durham, North Carolina, United States | |
| Contact: Catherine Foss 919-668-6530 catherine.foss@duke.edu | |
| Principal Investigator: John Sundy, MD, PhD | |
| United States, Ohio | |
| Ohio State University Medical Center/ Columbus Children's Hospital | Recruiting |
| Columbus, Ohio, United States | |
| Contact: Janice Drake 614-366-2287 janice.drake@osumc.edu | |
| Principal Investigator: John Mastronarde, MD | |
| United States, Texas | |
| Baylor College of Medicine | Recruiting |
| Houston, Texas, United States | |
| Contact: Laura Bertrand 713-798-2681 tyler@bcm.tmc.edu | |
| Principal Investigator: Nicola Hanania, MD, FCCP | |
| United States, Vermont | |
| Northern New England Consortium | Recruiting |
| Colchester, Vermont, United States | |
| Contact: Stephanie Burns 802-847-2103 stephanie.burns@vtmednet.org | |
| Principal Investigator: Chrarles Irvin, PHD | |
| United States, Virginia | |
| University of Virginia | Recruiting |
| Charlottesville, Virginia, United States | |
| Contact: Donna Wolf 434-982-4086 dlw9t@virginia.edu | |
| Principal Investigator: William Teague | |
| Principal Investigator: | Janet Holbrook, PHD | Johns Hopkins University |
More Information
No publications provided
| Responsible Party: | Robert A. Wise, M.D., Robert A. Wise, M.D, American Lung Association Asthma Clinical Research Centers |
| ClinicalTrials.gov Identifier: | NCT01629823 History of Changes |
| Other Study ID Numbers: | ALA-ACRC-13, U01HL108730 |
| Study First Received: | June 25, 2012 |
| Last Updated: | May 4, 2013 |
| Health Authority: | United States: Institutional Review Board United States: Federal Government United States: Food and Drug Administration |
Additional relevant MeSH terms:
|
Asthma Bronchial Diseases Respiratory Tract Diseases Lung Diseases, Obstructive Lung Diseases |
Respiratory Hypersensitivity Hypersensitivity, Immediate Hypersensitivity Immune System Diseases |
ClinicalTrials.gov processed this record on May 19, 2013