Increased Lung Volume as Controller Therapy for Asthma

• ClinicalTrials.gov Identifier: NCT02953431
• Recruitment Status: Recruiting
• First Posted: November 2, 2016
• Last Update Posted: August 3, 2020
• Sponsor: University of Vermont
• Collaborator: Icahn School of Medicine at Mount Sinai
• Information provided by (Responsible Party): Anne Dixon, University of Vermont

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Asthma	Device: CPAP	Phase 1; Phase 2

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Increased Lung Volume as Controller Therapy for Asthma
• Actual Study Start Date: May 7, 2018
• Estimated Primary Completion Date: September 2020
• Estimated Study Completion Date: September 2020

Arms and Interventions

Arm	Intervention/treatment
Placebo Comparator: Sham CPAP; Participants will be randomized to Sham CPAP	Device: CPAP; CPAP will be administered with a CPAP machine
Active Comparator: CPAP 10; Participants will be randomized to CPAP 10	Device: CPAP; CPAP will be administered with a CPAP machine

Outcome Measures

Primary Outcome Measures :

1. Change in impedance of lung in response to methacholine measured by forced oscillation [ Time Frame: Through study completion, an average of one week ]
   Average change in impedance in response to methacholine in participants assigned to Sham CPAP versus CPAP 10

Secondary Outcome Measures :

1. Change in spirometric lung function (FEV1 and FVC) [ Time Frame: Through study completion, an average of one week ]
   Average change in lung function in response to methacholine in participants assigned to Sham CPAP versus CPAP 10
2. Change in asthma control [ Time Frame: Through study completion, an average of one week ]
   Average change in asthma control in response to methacholine in participants assigned to Sham CPAP versus CPAP 10

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria for people with asthma:

1. Physician diagnosis of asthma
2. PC20 to methacholine < 16 mg/ml
3. Asthma diagnosis age >= 18 years
4. IgE < 100 IU/ml
5. Ages 18-65 years
6. 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)

Contacts and Locations

Contacts

Contact: Anne Dixon, BM BCh; 802 656 3525; anne.dixon@uvm.edu

Contact: Kevin Hodgdon; 802 847 8602; kevin.hodgdon@UVMHealth.org

Locations

United States, Vermont

Vermont Lung Center; Recruiting

Colchester, Vermont, United States, 05446

Contact: Kevin Hodgdon 802-847-8602 kevin.hodgdon@uvmhealth.org

Sponsors and Collaborators

University of Vermont

Icahn School of Medicine at Mount Sinai

Investigators

• Principal Investigator: Anne Dixon, BM BCh; University of Vermont

More Information

Publications of Results:

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.

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.

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.

• Responsible Party: Anne Dixon, Professor of Medicine, University of Vermont
• ClinicalTrials.gov Identifier: NCT02953431
• Other Study ID Numbers: 16-061
• First Posted: November 2, 2016
• Last Update Posted: August 3, 2020
• Last Verified: July 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Results will be published in the archival literature, and this will include a complete description of experimental and analytical methods used. All original data will be stored and available to interested investigators with appropriate regulatory approvals in place

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by Anne Dixon, University of Vermont:

Asthma; Obesity

Additional relevant MeSH terms:

Asthma; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases