Increased Lung Volume as Controller Therapy for Asthma

Study Overview
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Brief Summary
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This is an early phase clinical trial to test the efficacy of elevating lung volume with positive expiratory pressure (CPAP) as a controller therapy for asthma in patients with a BMI ≥ 30 kg/m2. There will be two phases to this trial. Phase I: In the first phase we will determine the optimal duration of CPAP that is effective as a controller therapy in asthma. Up to 9 participants will complete this this phase. Phase II: The 2nd phase will be a randomized double-blinded controlled trial of Sham CPAP versus CPAP 10 (using the duration of CPAP determined in phase I) as a controller therapy for asthma, and also to determine the effect o airway reactivity in healthy people with a BMI 30 kg/m2 and above. Twenty people with asthma and twenty controls will complete this phase.

Detailed Description
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The effect of 10 versus 0 cmH2O CPAP on airways responsiveness to inhaled methacholine will be studied using an adaptive 3+3 phase I/II study design. Dose Titration Phase (phase I): The efficacy of 8 hours of CPAP on airway responsiveness will be tested in three subjects. Efficacy will be defined as a 25% improvement in the impedance response to methacholine in all three subjects. If this occurs in all subjects, shorter durations of CPAP will be studied (4 hours then one hour). Conversely, if dose escalation is required, 3 nights, then 7 nights of CPAP will be studied. Randomized-controlled study phase (phase II): Participants will be randomized to CPAP 10 or Sham 0. The duration of CPAP will be determined in the dose titration phase. The effect on response to inhaled methacholine, lung function and asthma control will be determined in patients with asthma and a BMI ≥ 30 kg/m2, and also in healthy controls without asthma

Official Title
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Increased Lung Volume as Controller Therapy for Asthma

Conditions
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Asthma

Intervention / Treatment
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* Device: CPAP


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria for people with asthma: Physician diagnosis of asthma PC20 to methacholine < 16 mg/ml IgE < 100 IU/ml Ages 18-65 years BMI >=30 kg/m2 Inclusion Criteria for controls: No physician diagnosis of asthma PC20 to methacholine > 16 mg/ml IgE < 100 IU/ml Ages 18-65 years BMI >=30 kg/m2 Exclusion Criteria: FEV1 < 60 % predicted Other significant disease that in the opinion of the investigator would interfere with study. Inability to perform required testing. Smoking within last 6 months. ≥ 20 pack year smoking history Inability to provide informed consent Pregnancy Known obstructive sleep apnea/ high likelihood of obstructive sleep apnea Asthma exacerbation in the prior 6 weeks Stoke or heart attack in the prior 3 months Known aortic aneurysm Renal failure A known severe heart, vascular, liver, renal, or hematological disease Active allergic rhinitis Recent eye surgery (within the last month)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Sham CPAP<br>Participants will be randomized to Sham CPAP | Device: CPAP<br>* CPAP will be administered with a CPAP machine<br>|
| Active Comparator: CPAP 10<br>Participants will be randomized to CPAP 10 | Device: CPAP<br>* CPAP will be administered with a CPAP machine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in impedance of lung in response to methacholine measured by forced oscillation | Average change in impedance in response to methacholine in participants assigned to Sham CPAP versus CPAP 10 | Through study completion, an average of one week | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in spirometric lung function (FEV1 and FVC) | Average change in lung function in response to methacholine in participants assigned to Sham CPAP versus CPAP 10 | Through study completion, an average of one week | 
| Change in asthma control | Average change in asthma control in response to methacholine in participants assigned to Sham CPAP versus CPAP 10 | Through study completion, an average of one week | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Obesity