Asthma
Conditions
Brief summary
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
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).
Interventions
DEVICEContinuous Positive Airway Pressure (CPAP)
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.
DEVICEContinuous Positive Airway Pressure (CPAP) Sham
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.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Airway Reactivity From Baseline (Visit 1) and 4 Weeks (Visit 2) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Airway Inflammation From Baseline (Visit 1) and 4 Weeks (Visit 2) | 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. |
Countries
United States
Participant flow
Recruitment details
25 were excluded based on screening criteria, two subjects (one in each group) were lost to follow-up, two (one in each group) did not tolerate the equipment and two (one in each group) did not undergo Methacholine challenge at V2 due to the presence of asthma symptoms.
Participants by arm
| Arm | Count |
|---|---|
| CPAP Use of a CPAP machine for at least 5 days per week for 28 days
CPAP: 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. | 27 |
| CPAP Sham Use of a sham CPAP machine for at least 5 days per week for 28 days
CPAP Sham: 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. | 28 |
| Total | 55 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Did not tolerate intervention | 1 | 1 |
| Overall Study | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | CPAP | CPAP Sham | Total |
|---|---|---|---|
| Age, Continuous | 11.1 years STANDARD_DEVIATION 2.5 | 11.7 years STANDARD_DEVIATION 2.5 | 11.5 years STANDARD_DEVIATION 2.5 |
| Methacholine Bronchial Challenge | 2.9 mg/mL STANDARD_DEVIATION 4.5 | 3.2 mg/mL STANDARD_DEVIATION 4.3 | 3.09 mg/mL STANDARD_DEVIATION 4.38 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants | 8 Participants | 18 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 16 Participants | 16 Participants | 32 Participants |
| Region of Enrollment United States | 27 Participants | 28 Participants | 55 Participants |
| Sex: Female, Male Female | 10 Participants | 12 Participants | 22 Participants |
| Sex: Female, Male Male | 17 Participants | 16 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 29 | 0 / 30 |
| other Total, other adverse events | 5 / 29 | 3 / 30 |
| serious Total, serious adverse events | 0 / 29 | 0 / 30 |
Outcome results
Primary
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.
Time frame: baseline (visit 1) and 4 weeks (visit 2)
Population: One subject in each group did not undergo Methacholine challenge at V2 due to the presence of asthma symptoms
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CPAP | Change in Airway Reactivity From Baseline (Visit 1) and 4 Weeks (Visit 2) | Visit 1 | 3.0 mg/mL | Standard Deviation 4.6 |
| CPAP | Change in Airway Reactivity From Baseline (Visit 1) and 4 Weeks (Visit 2) | Visit 2 | 5.3 mg/mL | Standard Deviation 8.9 |
| CPAP Sham | Change in Airway Reactivity From Baseline (Visit 1) and 4 Weeks (Visit 2) | Visit 1 | 3.2 mg/mL | Standard Deviation 4.4 |
| CPAP Sham | Change in Airway Reactivity From Baseline (Visit 1) and 4 Weeks (Visit 2) | Visit 2 | 4.3 mg/mL | Standard Deviation 6.8 |
Secondary
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.
Time frame: baseline (visit 1) and 4 weeks (visit 2)
Population: The overall success rate in obtaining quality sputum samples was 57%; however, only 10 CPAP and 12 sham subjects had quality samples at both study visits.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| CPAP | Change in Airway Inflammation From Baseline (Visit 1) and 4 Weeks (Visit 2) | Study Visit 1 | 6.2 Percentage of sputum eosinophils | Standard Deviation 10.1 |
| CPAP | Change in Airway Inflammation From Baseline (Visit 1) and 4 Weeks (Visit 2) | Study Visit 2 | 3.6 Percentage of sputum eosinophils | Standard Deviation 6.4 |
| CPAP Sham | Change in Airway Inflammation From Baseline (Visit 1) and 4 Weeks (Visit 2) | Study Visit 1 | 3.9 Percentage of sputum eosinophils | Standard Deviation 5 |
| CPAP Sham | Change in Airway Inflammation From Baseline (Visit 1) and 4 Weeks (Visit 2) | Study Visit 2 | 5.4 Percentage of sputum eosinophils | Standard Deviation 8.2 |