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Trial registered on ANZCTR


Registration number
ACTRN12615000294550
Ethics application status
Approved
Date submitted
9/03/2015
Date registered
27/03/2015
Date last updated
12/06/2019
Date data sharing statement initially provided
12/06/2019
Date results information initially provided
12/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Understanding the role of acute exercise in modifying eosinophilic airway inflammation in asthma
Scientific title
Comparing the impact of acute vigorous intensity or moderate intensity exercise with rest, on airway and systemic inflammation, oxidative stress and antioxidants in adults with asthma: a randomised controlled trial
Secondary ID [1] 286163 0
Nil known
Universal Trial Number (UTN)
Trial acronym
EIA Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 294171 0
Condition category
Condition code
Respiratory 294499 294499 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
After attending a screening visit to confirm study eligibility, participants will wear an accelerometer on their wrist for one week to record usual physical activity levels. Participants will then attend two study visits on consecutive days.

VISIT 1:
Participants will be instructed to abstain from moderate-vigorous exercise for the two days prior to this visit and all physical activity for 12 hours prior to their visit. Participants will be instructed to withhold their asthma medications for 6-24 hours and anti-histamine medications for 3 days. Participants will need to fast for at least 2 hours prior to their visit. Upon arrival to the clinic participants will have their accelerometer collected, their weight checked and a venous blood sample collected. Exhaled nitric oxide (eNO) will be measured and spirometry performed. Sputum induction coupled with bronchial provocation will be performed over a standardised 15.5 minutes nebuliser time using 4.5% hypertonic saline.

VISIT 2:
Visit 2 will be conducted the day following visit 1. The participant will be required to refrain from physical activity and alcohol consumption since before visit 1, caffeine for at least 6 hours and food for 2 hours. Two hours prior to their scheduled visit, participants will be instructed to have their usual breakfast (without caffeine).

Participants will be randomised to complete either:
a) 40 minutes of moderate-intensity exercise (50-55% of heart rate reserve), plus 5 minute warm-up and 1 minute cool down.
b) 25 minutes of vigorous-intensity exercise (75-80% of heart rate reserve), plus 5 minute warm-up and 1 minute cool down; or
c) 30-minutes of rest in a chair

All participants will be provided with 400 micrograms salbutamol, inhaled via a valved holding chamber upon arrival for visit 2. Those randomised to complete one of the two exercise interventions will do so on a cycle ergometer, 20 minutes following administration of salbutamol.

Vigorous Intensity Exercise:
Participants will complete a 5 minute warm up, where the tension on the bicycle will be set to its minimum load. After the warm up, the tension on the cycle will be gradually increased until the desired heart rate is achieved (75-80% of heart rate reserve). Every four minutes the participant will stop cycling for 20 seconds but the timer will continue. Participant’s blood pressure, heart rate, SpO2, BORG dyspnoea rating and rating of perceived exertion will be recorded at 4 minute intervals and the values compared to the criteria to terminate the test. After 25 minutes the cycle will be returned to its minimum load for a 1 minute cool down. Immediately following the cool down, blood pressure, heart rate, SpO2, rating of perceived exertion, and dyspnoea rating will be recorded, while blood pressure, heart rate, SpO2, rating of perceived exertion and dyspnoea rating will be recorded again 5 and 10 minutes after completing the test. FEV1 will be measured 5-10 minutes following the cool down. If there is a >=10% reduction in FEV1 from baseline, or at patient request, the participant will be given 400 micrograms salbutamol, inhaled via a valved holding chamber .

Moderate Intensity Exercise:
Participants will complete a 5 minute warm up, where the tension on the bicycle will be set to its minimum load. After the warm up, the tension on the cycle will be gradually increased until the desired heart rate is achieved (50-55% of heart rate reserve). Every 10 minutes the participant will stop cycling for 1 minute but the timer will continue. Participant’s blood pressure, heart rate, SpO2, BORG dyspnoea rating and rating of perceived exertion will be recorded at 4 minute intervals and the values compared to the criteria to terminate the test. After 40 minutes the cycle will be returned to its minimum load for a 1 minute cool down. Immediately following the cool down, blood pressure, heart rate, SpO2, rating of perceived exertion and dyspnoea rating will be recorded, while blood pressure, heart rate, SpO2, rating of perceived exertion and dyspnoea rating will be recorded again 5 and 10 minutes after completing the test. FEV1 will be measured 5-10 minutes following the cool down. If there is a >=10% reduction in FEV1 from baseline, or at patient request, the participant will be given 400 micrograms salbutamo, inhaled via a valved holding chamber .

Following a short break, waist circumference will be measured. Participants will then undergo skin allergy testing and complete questionnaires related to asthma symptoms and characterisation, and exercise levels.

Two hours post-exercise/rest, participants will have a venous blood sample collected and eNO measured. Participants will then be provided with a standardised light lunch.

Four hours post exercise/rest, participants will have their blood pressure checked and a venous blood sample collected. eNO will be measured and spirometry performed. Sputum induction will be performed over a standardised 15.5 minutes nebuliser time using 4.5% hypertonic saline. Participant’s will submit a 4 day food diary and will then be discharged from the study.
Intervention code [1] 291169 0
Lifestyle
Intervention code [2] 291475 0
Treatment: Other
Comparator / control treatment
The comparator or control treatment will be no exercise, where the participant will rest in a chair for 30 minutes.
Control group
Active

Outcomes
Primary outcome [1] 294287 0
Induced sputum eosinophil count
Timepoint [1] 294287 0
One day pre versus 4 hours post intervention/control
Secondary outcome [1] 312945 0
Sputum leukocytes
Timepoint [1] 312945 0
One day pre versus 4 hours post intervention/control
Secondary outcome [2] 312946 0
Exhaled nitric oxide, measured using an exhaled nitric oxide breath analyser.
Timepoint [2] 312946 0
One day pre versus 4 hours post intervention/control
Secondary outcome [3] 312947 0
Plasma Interleukin-1ra
Timepoint [3] 312947 0
One day pre versus 4 hours post intervention/control
Secondary outcome [4] 312948 0
Plasma Interleukin-6
Timepoint [4] 312948 0
One day pre versus 4 hours post intervention/control
Secondary outcome [5] 312949 0
Plasma interleukin-10
Timepoint [5] 312949 0
One day pre versus 4 hours post intervention/control
Secondary outcome [6] 312950 0
Plasma nitric oxide
Timepoint [6] 312950 0
One day pre versus 4 hours post intervention/control
Secondary outcome [7] 312951 0
Red blood cell superoxide dismutase
Timepoint [7] 312951 0
One day pre versus 4 hours post intervention/control
Secondary outcome [8] 312952 0
Red blood cell glutathione peroxidase
Timepoint [8] 312952 0
One day pre versus 4 hours post intervention/control
Secondary outcome [9] 312953 0
Sputum interleukin-6
Timepoint [9] 312953 0
One day pre versus 4 hours post intervention/control
Secondary outcome [10] 312954 0
Sputum interleukin-5
Timepoint [10] 312954 0
One day pre versus 4 hours post intervention/control
Secondary outcome [11] 312955 0
Sputum interleukin-10
Timepoint [11] 312955 0
One day pre versus 4 hours post intervention/control
Secondary outcome [12] 312956 0
Sputum 8-isoprostane
Timepoint [12] 312956 0
One day pre versus 4 hours post intervention/control

Eligibility
Key inclusion criteria
1. Physician diagnosed asthma
2. Able to provide written informed consent
3. Females 18-55 years of age or males 18-45 years of age
4. Body mass index (BMI) <=40kg/m2
5. Not a current smoker (never smoker or quit at least 6 months ago)
6. Post-bronchodilator forced expiratory volume in 1 second (FEV1) >=50% predicted.
7. Approved for vigorous exercise by the study coordinator, according to the ESSA “Adult Pre-Exercise Screening Tool”.
Minimum age
18 Years
Maximum age
55 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Asthma is not the primary respiratory diagnosis
2. A moderate exacerbation (oral corticosteroid or antibiotic use) in the past four weeks or severe exacerbation (hospitalisation) in the past three months
3. Participation in a moderate-vigorous intensity exercise session within 2 days of the scheduled study visit.
4. Known cardiac condition
5. Musculoskeletal contraindication to exercise
6. Uncontrolled hypertension (blood pressure >180/100mmHg)
7. Cancer
8. Diabetes mellitus
9. Thyroid disorder
10. Taking cholesterol lowering medication or ß-blocker medication
11. Pregnancy or breastfeeding
12. Resting SpO2 <=95% on room air
13. Participation in an interventional research study in the last four weeks
14. Currently exercising at a moderate-intensity or greater for >90 mins/week
15. Subject has a clinically important medical illness (including serious psychological disorders) likely to interfere with management or participation in the study

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Upon arrival for visit 2 (intervention visit), participants will be assigned to the next available study number. Allocation will be performed by the randomisation being contained in sequentially numbered and sealed opaque envelopes, which will be created by an independent statistician and opened by the researcher immediately prior to the intervention being undertaken.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated sequence, using a randomisation table created by computer software.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The primary outcome is change in absolute sputum eosinophil count 4 hours post-exercise. We expect to observe a reduction in sputum eosinophils of 0.07+/-0.07×10^6/g cells following moderate-intensity exercise. Allowing for 15% of subjects not to produce an adequate sputum sample, with 20 subjects/group, total = 60 subjects, we will have 80% power to detect a change. ANOVA will be performed to examine the effects of exercise on systemic and airway inflammation. Associations between change in sputum eosinophils and markers of inflammation will be examined by correlation. P-values <0.05 will be considered statistically significant.

Recruitment
Recruitment status
Active, not recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 3440 0
Princess Alexandra Hospital - Woolloongabba
Recruitment postcode(s) [1] 9210 0
4102 - Woolloongabba

Funding & Sponsors
Funding source category [1] 290735 0
Charities/Societies/Foundations
Name [1] 290735 0
Thoracic Society of Australia and New Zealand
Address [1] 290735 0
Suite 405, Level 4, 5 Hunter Street, Sydney NSW 2000
Country [1] 290735 0
Australia
Funding source category [2] 296519 0
Charities/Societies/Foundations
Name [2] 296519 0
Asthma Australia
Address [2] 296519 0
Level 13, Tower B
799 Pacific Highway
Chatswood, NSW 2067
Australia
Country [2] 296519 0
Australia
Funding source category [3] 303021 0
University
Name [3] 303021 0
Priority Research Centre for Healthy Lungs, University of Newcastle
Address [3] 303021 0
Level 2 West,
HMRI Building
Lot 1 Kookaburra Circuit,
New Lambton Heights NSW 2305
Country [3] 303021 0
Australia
Primary sponsor type
Individual
Name
Dr Hayley Scott
Address
Lung and Allergy Research Centre
Level 5 West, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Country
Australia
Secondary sponsor category [1] 289424 0
Hospital
Name [1] 289424 0
Princess Alexandra Hospital
Address [1] 289424 0
237 Ipswich Road, Woolloongabba QLD 4102
Country [1] 289424 0
Australia
Secondary sponsor category [2] 289425 0
University
Name [2] 289425 0
The University of Queensland
Address [2] 289425 0
St Lucia QLD 4072
Country [2] 289425 0
Australia
Other collaborator category [1] 278347 0
Individual
Name [1] 278347 0
Prof John Upham
Address [1] 278347 0
Lung and Allergy Research Centre
Level 5 West, Translational Research Institute
37 Kent Street
Woolloongabba QLD 4102
Country [1] 278347 0
Australia
Other collaborator category [2] 278348 0
Individual
Name [2] 278348 0
A/Prof Lisa Wood
Address [2] 278348 0
Centre for Asthma & Respiratory Diseases,
Level 2 West,
Hunter Medical Research Institute
Lot 1 Kookaburra Circuit
New Lambton Heights NSW 2305
Country [2] 278348 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 292371 0
Metro South Human Research Ethics Committee
Ethics committee address [1] 292371 0
Centres for Health Research
Level 7, Translational Research Institute Building
37 Kent Street,
Woolloongabba QLD 4102
Ethics committee country [1] 292371 0
Australia
Date submitted for ethics approval [1] 292371 0
09/01/2015
Approval date [1] 292371 0
05/03/2015
Ethics approval number [1] 292371 0
HREC/15/QPAH/16

Summary
Brief summary
This study will examine the role of exercise in optimising asthma management. We will compare and contrast the effects
of two exercise intensities: a single exercise session at a moderate-intensity (i.e. exercising at the level of a brisk walk or
dancing) versus a single exercise session at a vigorous-intensity (more exhaustive, i.e. at the level of running or playing soccer). We will also compare these two exercise types with no exercise (control condition). We anticipate that while moderate-intensity
exercise will be beneficial to asthma, the effects of vigorous-intensity exercise are unknown. We will collect sputum samples from 60 adults with asthma, both before and 4 hours following their exercise or rest session, and blood samples before, and 2 and 4 hours following the exercise or rest session. These samples will provide a direct measure of inflammation and antioxidants, both in the airways and bloodstream, thus enabling us to quantify the benefit or consequence of each type of exercise on inflammation in adults with asthma.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 54874 0
Dr Hayley Scott
Address 54874 0
Centre for Healthy Lungs
Level 2 West, Hunter Medical Research Institute
Lot 1 , Kookaburra Circuit,
New Lambton Heights NSW 2305
Country 54874 0
Australia
Phone 54874 0
+61 2 4042 0113
Fax 54874 0
Email 54874 0
hayley.scott@newcastle.edu.au
Contact person for public queries
Name 54875 0
Dr Hayley Scott
Address 54875 0
Centre for Healthy Lungs
Level 2 West, Hunter Medical Research Institute
Lot 1 , Kookaburra Circuit,
New Lambton Heights NSW 2305
Country 54875 0
Australia
Phone 54875 0
+61 2 4042 0113
Fax 54875 0
Email 54875 0
hayley.scott@newcastle.edu.au
Contact person for scientific queries
Name 54876 0
Dr Hayley Scott
Address 54876 0
Centre for Healthy Lungs
Level 2 West, Hunter Medical Research Institute
Lot 1 , Kookaburra Circuit,
New Lambton Heights NSW 2305
Country 54876 0
Australia
Phone 54876 0
+61 2 4042 0113
Fax 54876 0
Email 54876 0
hayley.scott@newcastle.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual data will remain confidential.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
No
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary