PEEP as Rescue Therapy for Asthmatics With Elevated BMI

June 21, 2024 updated by: Anne Dixon, University of Vermont

Increased Lung Volume as Rescue Therapy for Asthma

The purpose of this study is to test the effect of increasing lung volume with a simple hand-held device to both prevent, and also to relieve, airway constriction in people with asthma and a BMI ≥ 30 kg/m2.

Twenty people with late onset non-allergic asthma and a BMI of ≥ 30 kg/m2 will be recruited. The efficacy of elevating lung volume on both preventing and reversing bronchoconstriction will be tested. Lung volume will be modulated by breathing out against a small level of resistance (positive expiratory pressure).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

This study will investigate whether PEEP can prevent and/or reverse bronchoconstriction in asthmatics with a BMI > 30 kg/m2.

People with late-onset non-allergic asthma that develops in the setting of obesity do not respond well to conventional asthma medications, likely because all treatments for asthma have been developed to treat early-onset allergic disease in lean patients. There is a critical need to understand the pathophysiology of airway disease in late-onset, non-allergic obese asthmatics, in order to develop therapies to target this disease.

Airway hyperresponsiveness (AHR) is a defining characteristic in asthma. Lung function tests in individuals with late onset asthma in the setting of obesity are suggestive of distal airway closure rather than airway narrowing as a cause of hyperresponsiveness; these individuals tend to have more collapsible lung peripheries than obese individuals who do not develop asthma. If late onset asthma in obesity is related to a tendency of airways to close, it should respond to therapies designed to keep airways open, such as Positive End-Expiratory Pressure (PEEP).

The purpose of this study is to investigate the efficacy of PEEP on prevention and reversal of bronchoconstriction in obese people with asthma. This will be achieved by investigating the efficacy of PEEP therapy on preventing and reversing bronchoconstriction in response to the inhalation of methacholine, while measuring changes in respiratory impedance using the forced oscillation method.

Participants will initially perform a conventional methacholine challenge test.

Participants will return for 2 visits in which methacholine will be administered concurrently with varying levels of PEEP (using PEEP to prevent bronchoconstriction) while measuring changes in respiratory impedance using the forced oscillation method.

Participants will return for another 2 visits in which PEEP will be administered subsequent to methacholine challenge (using PEEP to reverse bronchoconstriction) while measuring changes in respiratory impedance using the forced oscillation method.

These studies will be completed over 5 visits.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Vermont
      • Colchester, Vermont, United States, 05446
        • Vermont Lung Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • PC20 to methacholine < 16 mg/ml
  • Asthma diagnosis when ≥ 18 years of age
  • Serum Immunoglobulin E < 100 IU/ml
  • Ages ≥ 18 years
  • BMI ≥ 30 kg/m2

Exclusion Criteria:

  • Asthma exacerbation (defined as a hospitalization, ED visit, urgent care visit for asthma or new corticosteroids for asthma) in prior 6 weeks.
  • Forced Expiratory Volume in 1 second < 60 % predicted
  • Other significant disease that in the opinion of the investigator would interfere with study
  • Inability to perform required testing.
  • Smoking within last 6 months.
  • ≥ 20 pack year smoking history
  • Inability to provide informed consent
  • Pregnancy

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Rescue
Intervention: Positive expiratory pressure (PEEP) 10 will be applied after the administration of methacholine
Device: Positive Expiratory Pressure
Patient will exhale against positive expiratory pressure 0 mm or 10 mm while inhaling methacholine
Other Names:
  • PEEP
Experimental: Prophylaxis
Intervention: Positive expiratory pressure (PEEP) 10 will be applied during the administration of methacholine
Device: Positive Expiratory Pressure
Patient will exhale against positive expiratory pressure 0 mm or 10 mm while inhaling methacholine
Other Names:
  • PEEP
Placebo Comparator: No PEEP
Intervention: Positive expiratory pressure (PEEP) 0 will be applied during the administration of methacholine
Device: Positive Expiratory Pressure
Patient will exhale against positive expiratory pressure 0 mm or 10 mm while inhaling methacholine
Other Names:
  • PEEP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Central and Peripheral Elastance
Time Frame: The end of the experiment (at the 8-min time point)

Investigators compare changes in respiratory system elastance to methacholine. Respiratory system impedance was measured at the 8-min time point and fit with the two-compartment series model of respiratory mechanics. The elastances of the central and distal compartments obtained from good quality fits of this model are reported for each of the following conditions:

V2: PEP of 0 was administered during (0-4.5 min) and after (4.5-8 min) methacholine administration.

V3: PEP of 0 was administered during (0-4.5 min) and PEP of 10 cmH2O after (4.5-8 min) methacholine administration.

V4: This is a repeat of V2 above to test for stability of the response. V5: PEP of 10 cmH2O was administered both during (0-4.5 min) and after (4.5-8 min) methacholine administration.

V1 was a baseline visit to establish physiologic parameters required for conducting Visits 2-5. There are no outcome measures for Visit 1.
The end of the experiment (at the 8-min time point)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Respiratory symptoms
Time Frame: immediately before and after PEEP
Investigators will compare changes in respiratory symptoms across the two levels of PEEP (PEEP 10 and PEEP 0) for participants being exposed to PEEP during methacholine and PEEP after methacholine separately.
immediately before and after PEEP

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Vermont

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2016

Primary Completion (Actual)

April 1, 2019

Study Completion (Actual)

June 1, 2019

Study Registration Dates

First Submitted

February 23, 2016

First Submitted That Met QC Criteria

March 1, 2016

First Posted (Estimated)

March 2, 2016

Study Record Updates

Last Update Posted (Actual)

July 17, 2024

Last Update Submitted That Met QC Criteria

June 21, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • M16-060

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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 experimental data will be stored and available to interested investigators with appropriate regulatory approvals in place.

IPD Sharing Time Frame

Clinical study report published December 2021.

IPD Sharing Supporting Information Type

  • CSR

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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