Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000991314
Ethics application status
Approved
Date submitted
26/06/2017
Date registered
10/07/2017
Date last updated
22/06/2021
Date data sharing statement initially provided
15/05/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
The Impact of Varying Exercise Training Intensity on Clinical Asthma Outcomes and Inflammation in Adults with Asthma
Scientific title
The Impact of Varying Exercise Training Intensity on Clinical Asthma Outcomes and Inflammation in Adults with Asthma: A Randomised Controlled Trial
Secondary ID [1] 291949 0
None
Universal Trial Number (UTN)
Trial acronym
ETA Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Asthma 303486 0
Condition category
Condition code
Respiratory 302900 302900 0 0
Asthma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Screening Visit: Participants will be screened for study eligibility. This visit will include medical history, medication usage, height, weight, lung function, asthma control, exhaled nitric oxide (eNO), blood pressure and the ESSA pre-exercise screening questionnaire. This visit should take less than one hour to complete. Once eligibility has been confirmed, participants will be provided with an accelerometer to wear for 7 days and a semi-quantitative food diary to complete for four days prior to Visit 1.

Visit 1a: Participants will be instructed to abstain from moderate- and vigorous-intensity exercise for the two days prior, and all activity for 12 hours prior to Visit 1. Participants will be instructed to withhold their asthma medications for 6-24 hours and anti-histamine medications for 5 days. Participants will need to fast for at least 12 hours prior to their visit. On arrival to the clinic participants will have their accelerometer and food diary collected, their weight checked and a venous blood sample collected. Fractional exhaled nitric oxide (FeNO) 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. Body composition and bone density will be measured by dual-energy x-ray absorptiometry (DXA). Skin allergy testing will be completed for a panel of common environmental allergens (dust mite, grass, cockroach, moulds) and asthma, exercise and dietary questionnaires will be completed. This visit should take approximately 2.5 hours to complete and will be conducted by a research assistant or postdoctoral research fellow with experience in performing these procedures.

Visit 1b: At a separate appointment, VO2max testing will be conducted at The University of Newcastle campus by an exercise physiology intern with training in conducting VO2max measurements. Participants will perform a progressive exercise test on a treadmill. The test commences at an easy workload and becomes progressively harder each minute until the participant voluntarily ends the test or they reach pre-determined end criteria (e.g. HR target; R>1.15). Throughout the test, heart rate, oxygen consumption and ventilation are monitored continuously. In order to measure oxygen consumption and ventilation, participants wear a face mask and their expired air is sampled for analysis. The face mask allows participants to speak clearly so communication throughout the test is maintained. Participants can end the test at any stage.

Following VO2max testing, participants randomisation will be revealed. Participants will be randomised to complete either:
a) Three months of moderate-intensity exercise training, including at least 3 one hour exercise sessions/week involving activities that maintain heart rate between 55-70% HRmax; or
b) Three months of vigorous-intensity exercise training, including at least 3 one hour exercise sessions/week involving activities that maintain heart rate between 70-85% HRmax; or
c) Three months of the control condition (no intervention).

Visits 2a and 2b: Participants will return to the clinic following the three month intervention, to repeat all procedures completed during Visit 1a and 1b. Prior to these visits, participants will be instructed to wear an accelerometer for one week and complete a 4-day semi-quantitative food diary.

Participant Weekly Questionnaires
Participants will complete the ACQ6 and quantify their physical activity participation for the preceding week in an online questionnaire to be completed each week. This will assist with monitoring adherence to the intervention protocols.

Exercise Protocol
Participants will undertake three months of exercise training at The University of Newcastle campus. Participants will be required to complete three x 1 hour exercise sessions per week, with all sessions to be supervised to encourage attendance and compliance with maintaining the appropriate heart rate for each session. These one-on-one sessions will be supervised by exercise physiology intern students. Heart rate will be monitored and recorded throughout the entire session. Moderate-intensity exercise training sessions will be completed at 55-70% of HRmax, while vigorous-intensity exercise will be completed at 70-85% of HRmax. Exercise will be personalised to the patients preference of equipment using a combination of treadmills, cycle ergometers and elliptical ergometers. Participants randomised to the control intervention will be offered a pedometer to keep at the conclusion of the study.
Intervention code [1] 298212 0
Lifestyle
Intervention code [2] 298518 0
Treatment: Other
Comparator / control treatment
The comparator/control group will be no exercise, where the participant will be advised to maintain their usual physical activity levels for the duration of the intervention.
Control group
Active

Outcomes
Primary outcome [1] 302290 0
Juniper asthma-related quality of life questionnaire (AQLQ) score
Timepoint [1] 302290 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [1] 335386 0
Juniper Asthma Control Questionnaire (ACQ) score
Timepoint [1] 335386 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [2] 335387 0
Asthma exacerbations in the preceding three months, recorded by a patient recall questionnaire designed specifically for this study.
Timepoint [2] 335387 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [3] 335388 0
Number of symptom free days in the preceding month, recorded by a patient recall questionnaire designed specifically for this study.
Timepoint [3] 335388 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [4] 335389 0
Sputum leukocytes
Timepoint [4] 335389 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [5] 335390 0
Fractional exhaled nitric oxide (FeNO)
Timepoint [5] 335390 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [6] 335391 0
Serum Interleukin-1ra
Timepoint [6] 335391 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [7] 335392 0
Serum Interleukin-6
Timepoint [7] 335392 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [8] 335393 0
Serum Interleukin-10
Timepoint [8] 335393 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [9] 335659 0
Serum Interleukin-1beta
Timepoint [9] 335659 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [10] 335660 0
Serum Interleukin-4
Timepoint [10] 335660 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [11] 335661 0
Serum Interleukin-5
Timepoint [11] 335661 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [12] 335662 0
Serum Interleukin-8
Timepoint [12] 335662 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [13] 335663 0
Serum TNF-alpha
Timepoint [13] 335663 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [14] 335664 0
Blood eosinophils
Timepoint [14] 335664 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [15] 335665 0
Blood neutrophils
Timepoint [15] 335665 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [16] 335666 0
Sputum supernatant Interleukin-1beta
Timepoint [16] 335666 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [17] 335667 0
Sputum supernatant Interleukin-6
Timepoint [17] 335667 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [18] 335668 0
Sputum supernatant Interleukin-8
Timepoint [18] 335668 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [19] 335669 0
Sputum supernatant TNF-alpha
Timepoint [19] 335669 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [20] 336559 0
Change in moderate-intensity exercise levels, measured by 1 week of accelerometry
Timepoint [20] 336559 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [21] 336560 0
Change in vigorous-intensity exercise levels, measured by 1 week of accelerometry
Timepoint [21] 336560 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.
Secondary outcome [22] 336561 0
Change in total exercise level, measured by 1 week of accelerometry
Timepoint [22] 336561 0
Pre-intervention versus post-intervention. Data will be collected within 2 weeks of commencing the intervention and 1 week of completion of the intervention.

Eligibility
Key inclusion criteria
1. Physician diagnosed asthma
2. Able to provide written informed consent
4. Body mass index (BMI) <=40kg/m2 (due to increased risk of exercise-related complication in those with a 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. Deemed suitable for vigorous-intensity exercise by the study coordinator, according to the ESSA “Adult Pre-Exercise Screening Tool”.
Minimum age
18 Years
Maximum age
55 Years
Sex
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- or vigorous-intensity exercise session within 2 days of the
scheduled study visits.
4. Known cardiac condition contraindicated for exercise
5. Musculoskeletal contraindication to exercise
6. Uncontrolled hypertension (blood pressure >180/100mmHg)
7. Cancer
8. Diabetes mellitus
9. Taking cholesterol lowering medication
10. Pregnancy or breastfeeding
11. Resting SpO2 <=95% on room air
12. Participation in an interventional research study in the last four weeks
13. Currently exercising at a moderate-intensity or greater for >90 mins/week
14. 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)
Following completion of Visit 1b, participants will be assigned to the next available study
number. Allocation will be performed by the randomisation codes being contained in sequentially numbered and sealed opaque envelopes, which will be created by an independent statistician and opened by the research assistant.
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
Per-protocol analysis of covariance (ANCOVA) will be used to establish the effects of vigorous-intensity and moderate-intensity exercise on asthma-related quality of life questionnaire (AQLQ) score in addition to other clinical and inflammatory outcomes, relative to the control condition. Changes in primary and secondary outcomes will also be examined using Wilcoxon signed rank test or a paired t-test, divided by intervention group. The associations between change in AQLQ score and changes in inflammation will be determined by correlation. Changes in overall physical activity levels, as well as changes in moderate-intensity and vigorous-intensity exercise (measured by accelerometry) will be compared to changes in clinical asthma outcomes and inflammation. The proportion of participants experiencing clinically important improvements in AQLQ and asthma control questionnaire (ACQ) score in each group will be examined, to determine the clinical success of each intervention.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
24/07/2017
Actual
19/07/2017
Date of last participant enrolment
Anticipated
Actual
7/08/2019
Date of last data collection
Anticipated
Actual
18/12/2019
Sample size
Target
69
Accrual to date
Final
46
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 8284 0
Hunter Medical Research Institute - New Lambton Heights
Recruitment postcode(s) [1] 16344 0
2305 - New Lambton Heights

Funding & Sponsors
Funding source category [1] 296462 0
Charities/Societies/Foundations
Name [1] 296462 0
Asthma Australia
Country [1] 296462 0
Australia
Funding source category [2] 302787 0
Hospital
Name [2] 302787 0
John Hunter Hospital Charitable Trust
Country [2] 302787 0
Australia
Primary sponsor type
Other
Name
Hunter Medical Research Institute
Address
HMRI Building
Lot 1 Kookaburra Circuit
New Lambton Heights NSW 2305
Country
Australia
Secondary sponsor category [1] 295617 0
Individual
Name [1] 295617 0
Dr Hayley Scott
Address [1] 295617 0
Centre for Healthy Lungs
Level 2 West, HMRI Building
Lot 1 Kookaburra Circuit,
New Lambton Heights NSW 2305
Country [1] 295617 0
Australia
Secondary sponsor category [2] 295618 0
Individual
Name [2] 295618 0
Prof John Upham
Address [2] 295618 0
Lung and Allergy Research Centre,
37 Kent Street,
Woolloongabba QLD 4102
Country [2] 295618 0
Australia
Secondary sponsor category [3] 295619 0
Individual
Name [3] 295619 0
Prof Lisa Wood
Address [3] 295619 0
Centre for Healthy Lungs
Level 2 West, HMRI Building
Lot 1 Kookaburra Circuit,
New Lambton Heights NSW 2305
Country [3] 295619 0
Australia
Secondary sponsor category [4] 295620 0
Individual
Name [4] 295620 0
Prof Robin Callister
Address [4] 295620 0
Priority Research Centre for Physical Activity and Nutrition,
Level 3, ATC Building
University of Newcastle,
University Drive,
Callaghan NSW 2308
Country [4] 295620 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297686 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 297686 0
Ethics committee country [1] 297686 0
Australia
Date submitted for ethics approval [1] 297686 0
31/03/2017
Approval date [1] 297686 0
15/06/2017
Ethics approval number [1] 297686 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 74822 0
Dr Hayley Scott
Address 74822 0
Centre for Healthy Lungs,
Level 2 West, HMRI Building
Lot 1 Kookaburra Circuit,
New Lambton Heights NSW 2305
Country 74822 0
Australia
Phone 74822 0
+61 2 4042 0113
Fax 74822 0
+61 2 4042 0046
Email 74822 0
[email protected]
Contact person for public queries
Name 74823 0
Hayley Scott
Address 74823 0
Centre for Healthy Lungs,
Level 2 West, HMRI Building
Lot 1 Kookaburra Circuit,
New Lambton Heights NSW 2305
Country 74823 0
Australia
Phone 74823 0
+61 2 4042 0113
Fax 74823 0
+61 2 4042 0046
Email 74823 0
[email protected]
Contact person for scientific queries
Name 74824 0
Hayley Scott
Address 74824 0
Centre for Healthy Lungs,
Level 2 West, HMRI Building
Lot 1 Kookaburra Circuit,
New Lambton Heights NSW 2305
Country 74824 0
Australia
Phone 74824 0
+61 2 4042 0113
Fax 74824 0
+61 2 4042 0046
Email 74824 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Participant individual data will remain confidential within the study team.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.