Modulation Of Airway Reactivity With Chronic Mechanical Strain

Study Overview
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Brief Summary
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The purpose of this study is to see if the use of a machine called CPAP will help children with asthma breathe better. CPAP is a machine that produces airflow to help people with breathing problems. To use it, you will wear a mask connected by a hose to the CPAP machine. We believe that use of CPAP may be a treatment for children with asthma.

Detailed Description
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During the previous funding period of this project, our laboratory demonstrated that chronic mechanical strain imposed on the airways in vivo using continuous positive airway pressure (CPAP) results in a dramatic reduction in airway reactivity in vivo in mice, ferrets and rabbits1-3. Lungs, airways and airway smooth muscle (ASM) tissues isolated from CPAP-treated animals studied in vitro exhibited lower responsiveness to bronchoconstrictors1-3. We also observed this suppression of airway responsiveness by chronic mechanical strain in a rabbit model of allergic asthma5. These animal studies led to a small clinical trial in which adults with asthma were treated with nocturnal CPAP for 1 week. CPAP caused a significant reduction in airway reactivity in these patients6. This novel approach for treating airway hyper-reactivity is currently being evaluated in a NIH multi-center Phase II clinical trial of adults with mild to moderate asthma (U01 HL108730).

Official Title
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Modulation Of Airway Reactivity With Chronic Mechanical Strain

Conditions
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Asthma

Intervention / Treatment
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* Device: Continuous Positive Airway Pressure (CPAP)
* Device: Continuous Positive Airway Pressure (CPAP) Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children 8-17 yrs olds with severe asthma (N=120) will be recruited from the Pediatric High Risk Asthma Clinic and Pulmonary Clinics at Riley Hospital for Children at Indiana University Health. Severe asthma will be defined by the need for medication therapies following steps 4-6 according to the National Institutes of Health's Asthma Care Quick Reference, September 2012 or high dose of inhaled corticosteroids On a stable regimen of asthma medications for at least 8 weeks prior to enrollment without systemic corticosteroids for ≥ 4 weeks Exclusion Criteria: Obese (>95% predicted BMI) Congenital heart disease or chronic lung disease History of pneumothorax Inability to perform pulmonary function testing Oxygen saturation <93% forced expiratory volume at one second (FEV1) <70% predicted Provocative concentration causing a 20% drop in FEV1 from baseline (PC20) ≥16 mg/ml of methacholine.

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 17 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Continuous Positive Airway Pressure (CPAP)<br>Use of a CPAP machine for at least 5 days per week for 28 days | Device: Continuous Positive Airway Pressure (CPAP)<br>* Subjects assigned to this group will be asked to use the CPAP machine for a minimum of 4 hours/night at least 5 days/week for a total of 4 weeks.<br>|
| Sham Comparator: Continuous Positive Airway Pressure (CPAP) Sham<br>Use of a sham CPAP machine for at least 5 days per week for 28 days | Device: Continuous Positive Airway Pressure (CPAP) Sham<br>* Subjects assigned to this group will be asked to use the CPAP Sham machine for a minimum of 4 hours/night at least 5 days/week for a total of 4 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Airway Reactivity From Baseline (Visit 1) and 4 Weeks (Visit 2) | The change in airway reactivity measured prior to and after 4 weeks of either CPAP or SHAM treatment. Methacholine bronchial challenge was performed using the 5-breath protocol (DeVilbiss646 with KoKo dosimeter: 9 μL/breath) with quadrupling concentrations starting with 0.0625 mg/mL and continuing until FEV1 decreased by 20% (PC20) or Methacholine concentration of 16 mg/mL was inhaled. | baseline (visit 1) and 4 weeks (visit 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Airway Inflammation From Baseline (Visit 1) and 4 Weeks (Visit 2) | Airway Inflammation assessed as the change in the percentage eosinophils in the induced sputum measured prior to and after 4 weeks of Continuous Positive Airway Pressure (CPAP) or sham CPAP treatment. | baseline (visit 1) and 4 weeks (visit 2) |