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

Asthma Clinical Trial

— CPAP  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT01629823
• Other study ID #: ALA-ACRC-13
• Secondary ID: U01HL108730
• Status: Active, not recruiting
• Phase: Phase 2
• First received: June 25, 2012
• Last updated: August 17, 2015
• Start date: July 2012

Study information

• Verified date: August 2015
• Source: American Lung Association Asthma Clinical Research Centers
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review BoardUnited States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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 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.

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 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).

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 200
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asthma

Intervention

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.

Locations

Country	Name	City	State
United States	University of Virginia	Charlottesville	Virginia
United States	Illinois Consortium	Chicago	Illinois
United States	Northern New England Consortium	Colchester	Vermont
United States	Ohio State University Medical Center/ Columbus Children's Hospital	Columbus	Ohio
United States	National Jewish Health	Denver	Colorado
United States	Duke University Medical Center	Durham	North Carolina
United States	Hofstra University School of Medicine	Hempstead	New York
United States	Baylor College of Medicine	Houston	Texas
United States	St. Vincent Hospital and Health Care Center, Inc	Indianapolis	Indiana
United States	Nemours Children's Clinic	Jacksonville	Florida
United States	University of Missouri, Kansas City School of Medicine	Kansas City	Missouri
United States	University of Miami/ University of South Florida	Miami	Florida
United States	Louisiana State University Health Sciences Center, The Ernest N. Morial Asthma, Allergy and Respiratory Disease Center	New Orleans	Louisiana
United States	Columbia University - New York University Consortium	New York	New York
United States	University of California, San Diego	San Diego	California
United States	Washington University/ St. Louis University	St Louis	Missouri
United States	University of Arizona	Tucson	Arizona
United States	New York Medical College	Valhalla	New York

Sponsors (2)

Lead Sponsor	Collaborator
American Lung Association Asthma Clinical Research Centers	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Methacholine reactivity	Airways reactivity will be measured with methacholine challenge testing, following ATS guidelines using the dosimeter technique .	16 weeks	No