Mediator Release During Exercise-induced Bronchoconstriction

January 28, 2019 updated by: Hannah Marshall, Brunel University
This study will compare the inflammatory response in induced vs inhibited exercise induced bronchoconstriction (EIB) in patients with a medical diagnosis of asthma/EIB. Urinary and plasma samples will be analysed to compare the mediator release in each condition, alongside changes in lung function.

Study Overview

Detailed Description

Exercise induced-bronchoconstriction (EIB) is a transient narrowing of the airways that occurs during or shortly after strenuous exercise. The prevalence of EIB in asthmatic patients is estimated around 30-50%, but EIB can also occur in individuals without asthma (especially children, army recruit forces, and elite athletes). Controversy remains about the causative mediators in the bronchoconstrictive response. Technological advancement in mass spectrometry has opened new avenues in the quantitative measurement of small endogenous metabolites in biological fluids (including urine and blood), which may provide insights into the pathophysiology of EIB and direct future therapeutic targets.

Utilising novel techniques in the analysis of inflammatory mediators in urine and blood, this study aims to conduct the most comprehensive analysis of mediator release during EIB to date.

Participants will attend a screening visit during which they will complete an exercise challenge (to determine the presence of EIB). A skin prick test will also be conducted to establish the atopic status of the participants. Following the screening visit, patients with EIB will be invited to complete a randomised cross-over study, where they will perform two further exercise challenges on separate days: one while inhaling temperate dry air, and one while inhaling hot humid air (the latter is known to inhibit EIB). Lung function and breathing discomfort will be recorded, and urine and blood samples will be collected, before and at various time points after exercise. As a control condition, participants will also attend one visit during which no exercise will be performed.

Participants aged 18-50yr, with diagnosed asthma and/or EIB, will be included in the study. 12 participants will complete 4 visits (lasting between 90 min and 4.5h). The study will take place on Brunel University London campus, Uxbridge. Urine and blood samples will be sent to the Karolinska Institutet, Stockholm, Sweden for analysis.

Study Type

Interventional

Enrollment (Anticipated)

12

Phase

  • Not Applicable

Contacts and Locations

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

Study Contact

Study Contact Backup

Study Locations

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 to 50 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Able to understand the study instructions
  • Willing and able to give informed consent
  • Aged 18-50yr
  • Physician-diagnosed asthma and/or EIB
  • Participants that demonstrate EIB at the screening visit (i.e., those who have a fall in FEV1 20% to 50%) will be eligible for the full study.

Exclusion Criteria:

  • Any chronic medical condition other than asthma or EIB
  • Baseline FEV1 <70% predicted
  • Exacerbation of asthma or respiratory infection within the last 4 wk
  • Individuals who have varied their inhaled corticosteroid medication within the last 4 wk
  • History of anaphylaxis
  • Current smokers
  • Pregnancy
  • History of cardiovascular disease
  • Injury that would prevent exercise on a cycle ergometer
  • Medical contraindication to perform strenuous exercise
  • Required oral corticosteroids in the past 3 months
  • Any blood borne disease

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: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Exercise induced bronchoconstriction
An exercise challenge will then be performed according to international guidelines. The exercise will consist of 8 minutes of cycling on a cycle ergometer while breathing medical grade dry air from a reservoir (Douglas bag) via a two-way non-rebreathing valve. The workload will be increased progressively over the first 2 minutes, and will then be maintained for 6 minutes at a target workload (in Watts) of [53.76 * measured forced expiratory volume in 1 sec (FEV1)-11.07].
Participants will exercise whilst inhaling dry-air, this is known to exacerbate the bronchoconstrictive response.
Other Names:
  • Induced bronchoconstriction
Active Comparator: Inhibited EIB
An exercise challenge will then be performed according to international guidelines. The exercise will consist of 8 minutes of cycling on a cycle ergometer while warm-humid air from a reservoir (Douglas bag) via a two-way non-rebreathing valve. The workload will be increased progressively over the first 2 minutes, and will then be maintained for 6 minutes at a target workload (in Watts) of [53.76 * measured forced expiratory volume in 1 sec (FEV1)-11.07].
Participants will perform the exercise-test whilst inhaling warm-humid air. This is known to inhibit the EIB response and will provide a direct comparison group for the EIB condition.
Other Names:
  • Exercise-control
No Intervention: Control
Participants will attend the laboratory but no exercise trial will be performed.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in the concentration of inflammatory mediator metabolites in urine
Time Frame: Urine sample will be collected 45 minutes and immediately prior to the exercise challenges (or controlled resting period) and at 45, 90, 135 and 180 minutes post-exercise.
Concentration of metabolites of prostaglandin-D2, Cysteinyl-Leukotrienes, prostaglandin-E2, prostacyclin, thromboxane and isoprostanes will be expressed as pg per mmol of creatinine.
Urine sample will be collected 45 minutes and immediately prior to the exercise challenges (or controlled resting period) and at 45, 90, 135 and 180 minutes post-exercise.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in the concentration of inflammatory mediator metabolites in blood plasma
Time Frame: Urine sample will be collected 45 minutes and immediately prior to the exercise challenges (or controlled resting period) and at 45, 90, 135 and 180 minutes post-exercise.
Concentration of tryptase and pro-inflammatory cytokines measured from blood plasma samples.
Urine sample will be collected 45 minutes and immediately prior to the exercise challenges (or controlled resting period) and at 45, 90, 135 and 180 minutes post-exercise.
Forced vital capacity (FVC) manoeuvres using spirometry
Time Frame: Spirometry will be performed 45 minutes and immediately prior to the exercise challenges (or controlled resting period) and at 45, 90, 135 and 180 minutes post-exercise.
Forced expiratory volume in one second (FEV1) measured in litres will be used to determine the severity of EIB from baseline to post-exercise challenge.
Spirometry will be performed 45 minutes and immediately prior to the exercise challenges (or controlled resting period) and at 45, 90, 135 and 180 minutes post-exercise.
Breathing rate
Time Frame: Continuous recording throughout 8-min exercise test using the online breath-by-breath analysis system.
Breathing rate (breaths per minute) will be recorded throughout exercise to control intensity between trials.
Continuous recording throughout 8-min exercise test using the online breath-by-breath analysis system.
Heart rate
Time Frame: Continuous recording continuously throughout the 8-min exercise test using short-range radiotelemetry using a chest belt worn by the participant.
Heart rate (beats per minute) will be recorded throughout the exercise challenge test to control intensity between trials.
Continuous recording continuously throughout the 8-min exercise test using short-range radiotelemetry using a chest belt worn by the participant.
Rating of breathing discomfort
Time Frame: Breathing discomfort severity ratings will be recorded every 2 minutes throughout the 8 min exercise test (a total of 4 measurements)
Modified Borg scale (0- no discomfort, 10- severe discomfort).
Breathing discomfort severity ratings will be recorded every 2 minutes throughout the 8 min exercise test (a total of 4 measurements)
Description of breathing discomfort
Time Frame: A description of breathing discomfort will be recorded every 2 minutes throughout the 8 min exercise test (a total of 4 measurements)
Descriptors from patients to describe the level of discomfort - i.e. 'my chest is tight'.
A description of breathing discomfort will be recorded every 2 minutes throughout the 8 min exercise test (a total of 4 measurements)

Collaborators and Investigators

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

Collaborators

Investigators

  • Principal Investigator: Hannah Marshall, MSc, Brunel University

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 (Actual)

November 1, 2018

Primary Completion (Anticipated)

March 1, 2020

Study Completion (Anticipated)

March 1, 2020

Study Registration Dates

First Submitted

April 20, 2018

First Submitted That Met QC Criteria

May 11, 2018

First Posted (Actual)

May 14, 2018

Study Record Updates

Last Update Posted (Actual)

January 29, 2019

Last Update Submitted That Met QC Criteria

January 28, 2019

Last Verified

January 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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