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Mediator Release During Exercise-induced Bronchoconstriction

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ClinicalTrials.gov Identifier: NCT03524053
Recruitment Status : Recruiting
First Posted : May 14, 2018
Last Update Posted : January 29, 2019
Sponsor:
Collaborator:
Karolinska Institutet
Information provided by (Responsible Party):
Hannah Marshall, Brunel University

Tracking Information
First Submitted Date  ICMJE April 20, 2018
First Posted Date  ICMJE May 14, 2018
Last Update Posted Date January 29, 2019
Actual Study Start Date  ICMJE November 1, 2018
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 11, 2018)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03524053 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: May 11, 2018)
  • 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.
  • 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.
  • 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.
  • 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.
  • 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).
  • 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'.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Mediator Release During Exercise-induced Bronchoconstriction
Official Title  ICMJE Mediator Release During Exercise-induced Bronchoconstriction
Brief 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.
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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description:
Patients will undertake 3 separate conditions in a randomised order.
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Exercise Induced Asthma
Intervention  ICMJE
  • Other: Exercise induced bronchoconstriction
    Participants will exercise whilst inhaling dry-air, this is known to exacerbate the bronchoconstrictive response.
    Other Name: Induced bronchoconstriction
  • Other: 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.
    Other Name: Exercise-control
Study Arms  ICMJE
  • 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].
    Intervention: Other: Exercise 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].
    Intervention: Other: Inhibited EIB
  • No Intervention: Control
    Participants will attend the laboratory but no exercise trial will be performed.
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 11, 2018)
12
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE March 2020
Estimated Primary Completion Date March 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 50 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Hannah Marshall, MSc +447584168742 hannah.marshall@brunel.ac.uk
Contact: Pascale Kippelen, PhD 01895267649 pascale.kippelen@brunel.ac.uk
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03524053
Other Study ID Numbers  ICMJE 8666
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Hannah Marshall, Brunel University
Study Sponsor  ICMJE Brunel University
Collaborators  ICMJE Karolinska Institutet
Investigators  ICMJE
Principal Investigator: Hannah Marshall, MSc Brunel University
PRS Account Brunel University
Verification Date January 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP