Mediator Release During Exercise-induced Bronchoconstriction

Exercise Induced Asthma Clinical Trial

Official title:

Mediator Release During Exercise-induced Bronchoconstriction

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03524053
• Other study ID #: 8666
• Status: Recruiting
• Phase: N/A
• Start date: November 1, 2018
• Est. completion date: March 2020

Study information

• Verified date: January 2019
• Source: Brunel University
• Contact: Hannah Marshall, MSc
• Phone: +447584168742
• Email: hannah.marshall[@]brunel.ac.uk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 12
• Est. completion date: March 2020
• Est. primary completion date: March 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Asthma, Exercise-Induced
• Exercise Induced Asthma

Intervention

Other:
• Exercise induced bronchoconstriction
Participants will exercise whilst inhaling dry-air, this is known to exacerbate the bronchoconstrictive response.
• Inhibited EIB
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.

Locations

Country	Name	City	State
United Kingdom	Brunel University London	Uxbridge	Middlesex

Sponsors (2)

Lead Sponsor	Collaborator
Brunel University	Karolinska Institutet

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in the concentration of inflammatory mediator metabolites in urine	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	Changes in the concentration of inflammatory mediator metabolites in blood plasma	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.
Secondary	Forced vital capacity (FVC) manoeuvres using spirometry	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.
Secondary	Breathing rate	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.
Secondary	Heart rate	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.
Secondary	Rating of breathing discomfort	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)
Secondary	Description of breathing discomfort	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)