Clinical trial NCT02953431: Increased Lung Volume as Controller Therapy for Asthma
Official title: Increased Lung Volume as Controller Therapy for Asthma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Asthma
Keywords: Asthma
Obesity
Lead sponsor: University of Vermont
Sponsor class: OTHER
Collaborators: name: Icahn School of Medicine at Mount Sinai
First posted: 2016-11-02
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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

Eligibility criteria: 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)

Primary outcomes:
measure: Change in impedance of lung in response to methacholine measured by forced oscillation
timeFrame: Through study completion, an average of one week
Secondary outcomes:
measure: Change in spirometric lung function (FEV1 and FVC)
timeFrame: Through study completion, an average of one week
measure: Change in asthma control
timeFrame: Through study completion, an average of one week
Other outcomes:
Locations:
city: Colchester
country: United States
facility: Vermont Lung Center
state: Vermont
Study officials:
affiliation: University of Vermont
name: Anne Dixon, BM BCh
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bates JH, Dixon AE. Potential role of the airway wall in the asthma of obesity. J Appl Physiol (1985). 2015 Jan 1;118(1):36-41. doi: 10.1152/japplphysiol.00684.2014. Epub 2014 Oct 23.
citation: Chapman DG, Irvin CG, Kaminsky DA, Forgione PM, Bates JH, Dixon AE. Influence of distinct asthma phenotypes on lung function following weight loss in the obese. Respirology. 2014 Nov;19(8):1170-7. doi: 10.1111/resp.12368. Epub 2014 Aug 19.
citation: Al-Alwan A, Bates JH, Chapman DG, Kaminsky DA, DeSarno MJ, Irvin CG, Dixon AE. The nonallergic asthma of obesity. A matter of distal lung compliance. Am J Respir Crit Care Med. 2014 Jun 15;189(12):1494-502. doi: 10.1164/rccm.201401-0178OC.