Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

The Effect of Physical Exercise in a Cold Air Environment on Normal Volunteers and Asthmatic Patients (ALASCAIR1)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03840044
Recruitment Status : Not yet recruiting
First Posted : February 15, 2019
Last Update Posted : February 15, 2019
Sponsor:
Information provided by (Responsible Party):
Tatjana Decaesteker, KU Leuven

Brief Summary:

The purpose of the study is to compare airway physiologic reactions to physical exercise in a cold air environment (-5°C, 60% relative humidity) between normal volunteers and subjects with mild/moderate asthma. For this purpose, the investigators intend to evaluate the effect of a cold air exercise test on the Forced Expiratory Volume in 1 second (FEV1), respiratory symptoms, functional airway integrity, local and systemic inflammation and on the airway microbiome.

This study also features as an exploratory study for a subsequent interventional study in order to establish the feasibility of the cold air exercise protocol and to determine the extent of the effects in subjects with mild/moderate asthma.


Condition or disease Intervention/treatment Phase
Asthma, Exercise-Induced Other: Cold air exercise test Not Applicable

Detailed Description:

It is already demonstrated that exercising during cold air exposure and at a high altitude may induce asthmatic symptoms, a variable degree of airway obstruction and increased neutrophilic airway inflammation in asthmatic patients. Therefore, in this project, the investigators want to evaluate the feasibility, of a shorter standardized "cold air exercise test" (a submaximal exercise challenge in a controlled cold air (-5°C, relative humidity 60%) environment) and to compare the respiratory physiologic reactions to physical exercise during cold exposure between healthy volunteers and asthmatic patients. For this purpose, they intend to evaluate the effect of a cold air exercise test on FEV1, respiratory symptoms, functional airway integrity, local and systemic inflammation and on the airway microbiome.

This study features as an exploratory study for a subsequent interventional study, that will assess the protective effect of azithromycin versus placebo on the cold air exercise induced changes in patients with mild/moderate asthma (ALASCAIR2 study). The present preparatory study is needed to standardize the cold air exercise test in a controlled environment so that it would be possible to use it as challenge test in an interventional study and to identify the most appropriate design for such a study.

The primary objective of this study is to compare the proportional change in FEV1, pre to post a 90 minutes submaximal exercise in a cold air environment between healthy volunteers versus mild/moderate asthmatics, calculated as a time-weighted average over the 30 minutes post-exposure.

The primary endpoint is the change in FEV1, calculated as a time-weighted average over the 30 minutes after the cold exercise test. At each time point (pre-exposure, 5' post-exposure, and at 15, 25 and 35 minutes post-exposure), FEV1 (L) will be measured in triplicate.

They want to evaluate whether the exercise test in a cold air environment produces respiratory symptoms (such as nasal discharge or obstruction, dyspnea, cough and/or mucus production, etc.), has an impact on airway integrity (nasal patency, airflow obstruction, lung ventilation inhomogeneity & small airway dysfunction, bronchial hyperreactivity, cough reflex hypersensitivity), induces local or systemic inflammatory changes (biomarkers in nasal fluid, sputum and blood) or changes to the airway microbiome (in nasal fluid and sputum) in healthy volunteers and in mild/moderate asthmatics. The study group also want to compare the observed changes induced by the cold air exercise test between the healthy volunteers and the mild/moderate asthmatics.

The secondary endpoints of this study include the observed changes in (respiratory) symptom score, Peak Nasal Inspiratory Flow (PNIF), Forced Vital Capacity (FVC), Forced Expiratory Flow (FEF25-75), Fraction of Exhaled Nitric Oxide (FeNO), histamine provocative concentration causing 20% drop in FEV1 (PC20), cough threshold C2 & C5, sputum differential cell count, biomarkers in nasal fluid, sputum and blood, nasal and sputum microbial communities between the healthy volunteers and the mild/moderate asthmatics.


Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 40 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Healthy volunteers will be compared with asthmatic subjects
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Effect of Physical Exercise in a Cold Air Environment on Normal Volunteers and Asthmatic Patients
Estimated Study Start Date : February 2019
Estimated Primary Completion Date : February 2020
Estimated Study Completion Date : October 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Healthy volunteers
Healthy volunteers will perform the same protocol as foreseen for asthmatic patients. Both will perform the cold air exercise test with pre -and post-exposure evaluation of on FEV1, respiratory symptoms, functional airway integrity, local and systemic inflammation and on the airway microbiome.
Other: Cold air exercise test
Subjects will perform a submaximal 90 minutes exercise test in a controlled cold air environment (-5°C, 60% relative humidity) in a climate chamber with evaluation pre§/during*/post§ of heart rate (HR)§* and blood pressure (BP)§*, spirometry§*, PNIF§, FeNO§, electrocardiogram (ECG)§*, body & exhaled air temperature§*, capsaicin cough threshold test§, histamine bronchial challenge test§, and sampling of nasal fluid§, induced sputum§, and venous blood§.

Asthmatic subjects
Asthmatic patients will perform the same protocol as foreseen for healthy volunteers. They will perform the cold air exercise test with pre -and post-exposure evaluation of on FEV1, respiratory symptoms, functional airway integrity, local and systemic inflammation and on the airway microbiome.
Other: Cold air exercise test
Subjects will perform a submaximal 90 minutes exercise test in a controlled cold air environment (-5°C, 60% relative humidity) in a climate chamber with evaluation pre§/during*/post§ of heart rate (HR)§* and blood pressure (BP)§*, spirometry§*, PNIF§, FeNO§, electrocardiogram (ECG)§*, body & exhaled air temperature§*, capsaicin cough threshold test§, histamine bronchial challenge test§, and sampling of nasal fluid§, induced sputum§, and venous blood§.




Primary Outcome Measures :
  1. Change in Forced Expiratory Volume in 1 seconds (FEV1) [ Time Frame: pre-, 5, 15, 25 and 35 minutes, 24 hours and 1 week post-exposure ]
    Change in FEV1, calculated as a time-weighted average over the 35 minutes after the cold air exercise test and 24 hours and 1 week post-exposure. A maximal fall of 10% will be considered as positive response


Secondary Outcome Measures :
  1. Changes in asthma control [ Time Frame: Pre-exposure and immediately, 24 hours and 1 week post-exposure ]
    Asthma control will be determined using the Asthma Control Questionnaire (ACQ-6), including 6 questions. Each question will be scored from 0-6 and added together. This final score will be divided by the number of questions. If ACQ-6 < 0.75 = controlled asthma, ACQ-6 from 0.75-1.5 = partly controlled asthma and ACQ-6 > 1.5 = uncontrolled asthma.

  2. Changes in respiratory symptom score [ Time Frame: Pre-exposure and immediately, 24 hours and 1 week post-exposure ]
    The degree of dyspnea will be determined using Borg scale. This Borg scale is 0 to 10 rated scale. With 0 no dyspnea and 10 complete dyspnea.

  3. Cough hypersensitivity [ Time Frame: Pre-exposure and 24 hours and 1 week post-exposure ]
    Cough hypersensitivity (Capsaicin cough threshold) will be measured using a capsaicin challenge test. The concentrations (µmol/l) which provokes 2 coughs (C2) and 10 coughs (C10) will be recorded and will be compared before and after cold air exposure.

  4. Bronchial hyperreactivity [ Time Frame: Pre-exposure and 1 week post-exposure ]
    Bronchial hyperreactivity will be measured using a histamine provocation. Bronchial hyperreactivity will be confirmed when there is a drop of 20% in FEV1 post histamine provocation (PC20).

  5. Nasal hyperreactivity [ Time Frame: Pre-exposure and immediately and 24 hours post-exposure ]
    Nasal hyperreactivity will be measured using a PNIF measurement. Nasal hyperreactivity will be confirmed when there is a drop of 20% in PNIF.

  6. Airway inflammation [ Time Frame: Pre-exposure and 24 hours and 1 week post-exposure ]
    Bronchial airway inflammation. Differential cell count will be performed on sputum samples, determining eosinophilic (>3% eosinophils, <61% neutrophils), neutrophilic (<3% eosinophils and >61% neutrophils), pauci-granulocytic (<3% eosinophils and <61% neutrophils) and mixed granulocytic airway inflammation (>3% eosinophils and >61% neutrophils).

  7. Cytokine pattern in the airways [ Time Frame: Pre-exposure and 24 hours and 1 week post-exposure ]
    Cytokines concentrations (pg/ml) will also be determined in sputum supernatant using a U-plex assay.

  8. Biomarkers for airway inflammation [ Time Frame: Pre-exposure and 24 hours and 1 week post-exposure ]
    FeNO will be used as biomarker for eosinophilic airway inflammation. FeNO < 25 ppb = eosinophilic inflammation less likely, FeNO between 25 and 50 ppm = need further interpretation with additional clinical information, FeNO > 50 ppm = indication of eosinophilic airway inflammation (according to the American Thoracic Society guidelines)

  9. Nasal inflammation [ Time Frame: Pre-exposure and immediately and 24 hours post-exposure ]
    Cytokine concentrations (pg/ml) will be determined in the nasal fluid as biomarkers for nasal inflammation

  10. Systemic inflammation [ Time Frame: Pre-exposure and immediately, 24 hours and 1 week post-exposure ]
    The degree of system inflammation will be determined via differential blood cell count.

  11. Biomarkers for systemic inflammation [ Time Frame: Pre-exposure and immediately, 24 hours and 1 week post-exposure ]
    The degree of system inflammation will be determined via C-reactive protein (CRP) levels. Normal values for CRP are considered < 10 mg/ml.

  12. Changes in microbiome in lung and nose [ Time Frame: Pre-exposure and 1 week post-exposure ]
    The presence of 22 common respiratory viruses, 5 bacteria and 1 fungi will be determined using qualitative reverse transcription polymerase chain reaction (qRT-PCR) in sputum and nasal fluid. Pre and post-exposure microbiome patterns will be compared.

  13. Evaluation of the heart rate pattern [ Time Frame: Pre-exposure and during the 90 minutes cold air exposure ]
    Cardiovascular health will be evaluated by determining the heart rate pattern using ECG. Deviation from a normal ECG pattern will be recorded.

  14. Determining the exercise capacity [ Time Frame: Pre-exposure ]
    Exercise capacity will be checked. In a single test pre-exposure, the aerobic heart rate zone, anaerobic heart rate zone and maximal oxygen volume uptake (VO2max) heart rate zone will be evaluated to determine the exercise capacity



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

INCLUSION CRITERIA - healthy volunteers

  • age between 18 and 60 years at time of signing informed consent
  • BMI between 18-28 kg/m2
  • able to comply with study protocol, in the investigator's judgement
  • non-smoking or ex-smokers for at least 12 months with less than 10 pack years
  • no immunoglobulin E (IgE) mediated hypersensitivity
  • normal spirometry & normal ECG at screening

INCLUSION CRITERIA - asthmatic patients

  • age between 18 and 60 years at time of signing informed consent
  • BMI between 18-28 kg/m2
  • able to comply with study protocol, in the investigator's judgement
  • non-smoking or ex-smokers for at least 12 months with less than 10 pack years
  • physician-diagnosed asthma for more than 6 months
  • post bronchodilator FEV1 of ≥ 80% at screening
  • documented airway reversibility either by means of post bronchodilator reversibility of > 12% and > 200 ml or in the previous 6 months or by means of documented airway hyperresponsiveness (histamine PC20 <8 mg/ml) at screening
  • Asthma Control Questionnaire (ACQ) < 1,5
  • regular treatment with inhaled corticosteroids (ICS) with or without long-acting beta-agonists (LABA) (unchanged dose for at least 1 month)
  • normal ECG at screening

EXCLUSION CRITERIA - healthy volunteers

  • physician-diagnosed asthma or history of (post)infectious bronchial hyperreactivity
  • major pulmonary or cardiovascular disease
  • treatment with β-blockers
  • pregnancy

EXCLUSION CRITERIA - asthmatics patients

  • unable to produce sputum with sputum induction
  • previous history of intubation or admission to the intensive care unit due to asthma
  • severe asthma exacerbation within one year prior to screening visit
  • treatment with oral or systemic steroids within one year prior to screening visit
  • previous treatment with biologics for asthma
  • treatment with β-blockers
  • other major concurrent pulmonary (such as chronic obstructive pulmonary disease, cystic fibrosis, sarcoidosis, interstitial lung disease, Churg-Strauss syndrome, allergic bronchopulmonary aspergillosis, bronchiectasis) or cardiovascular disease
  • pregnancy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03840044


Contacts
Layout table for location contacts
Contact: Tatjana Decaesteker +3216377816 tatjana.decaesteker@kuleuven.be

Sponsors and Collaborators
KU Leuven
Investigators
Layout table for investigator information
Principal Investigator: Lieven Dupont, Prof. dr KU Leuven/ UZ Leuven

Layout table for additonal information
Responsible Party: Tatjana Decaesteker, Co-Principal Investigator, KU Leuven
ClinicalTrials.gov Identifier: NCT03840044     History of Changes
Other Study ID Numbers: s61661
First Posted: February 15, 2019    Key Record Dates
Last Update Posted: February 15, 2019
Last Verified: February 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Tatjana Decaesteker, KU Leuven:
Asthma
Exercise
Cold air exposure

Additional relevant MeSH terms:
Layout table for MeSH terms
Asthma, Exercise-Induced
Asthma
Bronchial Diseases
Respiratory Tract Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases