Increased Lung Volume as Controller Therapy for Asthma

University of Vermont60 enrolled

Overview

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.

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

Inclusion Criteria for people with asthma: 1. Physician diagnosis of asthma 2. PC20 to methacholine \< 16 mg/ml 3. IgE \< 100 IU/ml 4. Ages 18-65 years 5. BMI \>=30 kg/m2 Inclusion Criteria for controls: 1. No physician diagnosis of asthma 2. PC20 to methacholine \> 16 mg/ml 3. IgE \< 100 IU/ml 4. Ages 18-65 years 5. BMI \>=30 kg/m2 Exclusion Criteria: 1. FEV1 \< 60 % predicted 2. Other significant disease that in the opinion of the investigator would interfere with study. 3. Inability to perform required testing. 4. Smoking within last 6 months. 5. ≥ 20 pack year smoking history 6. Inability to provide informed consent 7. Pregnancy 8. Known obstructive sleep apnea/ high likelihood of obstructive sleep apnea 9. Asthma exacerbation in the prior 6 weeks 10. Stoke or heart attack in the prior 3 months 11. Known aortic aneurysm 12. Renal failure 13. A known severe heart, vascular, liver, renal, or hematological disease 14. Active allergic rhinitis 15. Recent eye surgery (within the last month)

Outcomes

Primary Outcomes

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

Time frame: Through study completion, an average of one week

Secondary Outcomes

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

Time frame: 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

Time frame: Through study completion, an average of one week

Increased Lung Volume as Controller Therapy for Asthma

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes