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Trial registered on ANZCTR


Registration number
ACTRN12617000460303
Ethics application status
Approved
Date submitted
28/02/2017
Date registered
30/03/2017
Date last updated
30/11/2018
Date data sharing statement initially provided
30/11/2018
Date results information initially provided
30/11/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Determining the minimum dose of exercise required to improve cardiorespiratory fitness in stroke survivors (ExDose).
Scientific title
Determining the minimum dose of exercise required to improve cardiorespiratory fitness in stroke survivors (ExDose).
Secondary ID [1] 291299 0
None
Universal Trial Number (UTN)
Trial acronym
ExDose
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 302265 0
Condition category
Condition code
Stroke 301859 301859 0 0
Ischaemic
Physical Medicine / Rehabilitation 301860 301860 0 0
Physiotherapy
Stroke 302154 302154 0 0
Haemorrhagic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Brief title: Home-based aerobic exercise program. 4 groups; Ex-Dose 1, Ex-Dose 2, Ex-Dose 3, Ex-Dose 4

The same intervention (home-based exercise aerobic exercise) will be delivered in all 4 arms of the trial, only the dose will differ.

Dose is defined as the total accumulated exercise time per week.
Ex-Dose 1 = 30 min/week (3 x 10min sessions)
Ex-Dose 2 = 45 min/week (3 x 15min sessions)
Ex-Dose 3 = 60 min/week (3 x 20min sessions)
Ex-Dose 4 = 75 min/week, (3 x 25min sessions)

Physical materials provided to participants:
A heart rate monitor (includes a chest strap and wrist watch e.g. Garmin Forerunner 25, or similar)
An iPad or Tablet (if they do not own a suitable device)
An information booklet and exercise program

The intervention consists of exercises designed to increase heart rate to required target zone. Exercises may include activities such as walking, marching, sit to stand exercises, mini-squats and combination exercises. Each exercise session will have a 5 minute warm up and cool down period. Exercise sessions will consist of short bouts of alternating high (target 85% HR max) and low (target 55% HR max) intensity activities. The length of the intensity bouts will progressively increase, to the target of 2 min low intensity/ 2 mins high intensity. Programs will take into account initial fitness level, degree of disability and participant exercise preference.

The intervention will be delivered by research team members with minimum qualifications of bachelor degrees in exercise and sports science, physical education, physiotherapy, or other allied health, who have been trained by the lead investigator.

All intervention sessions (home based aerobic exercise) will be supervised via the internet (telehealth) by research team members.

Frequency: 3 times per week
Time period: 8 weeks
Number of sessions: 24
Intensity: Target intensity of 55-85% of age –predicted maximum heart rate
Session Duration: The session duration will vary by group (Ex-Dose 1 = 10min/session; Ex-Dose 2 = 15min/session, Ex-Dose 3 = 20min/session, Ex-Dose 4 = 25min/session) plus 5 min warm up and 5 min cool down per session.
Location: in-home

The intervention will be personalised for each participant; based on their initial fitness, stroke severity, and exercise capacity such that the target heart rates are met in each session. Exercise programs may be adjusted individually if target intensities are not being met. Clinical judgement will be used to change or adapt programmed exercises if required while the overall dose is maintained.

Intervention adherence:
All exercise sessions will be supervised via telehealth, and heart rate data monitored in real time.
Intervention code [1] 297326 0
Rehabilitation
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 301286 0
Smallest dose of exercise required to increase cardiorespiratory fitness by 2ml.kg-1.min-1. Cardiorespiratory fitness will be measured using VO2 (peak) measured continuously with a portable wearable metabolic system (Cosmed K5, Italy) during a cycle ergometer graded exercise test. VO2peak is defined as the highest recorded oxygen consumption during any given 15sec epoch measured in L/min, and mL/kg/min.
Timepoint [1] 301286 0
8 weeks (end intervention)
Secondary outcome [1] 332201 0
Peak power output during cycle ergometer graded exercise test.
Power output is increased each step of the graded exercise test. Peak power is defined as the power output attempted in the final step of the graded exercise test, and expressed in watts (W).
Timepoint [1] 332201 0
8 weeks (end intervention)
Secondary outcome [2] 332202 0
Ventilatory threshold measured by the portable metabolic system (Cosmed K5) during the cycle ergometer graded exercise test.
Ventilatory threshold is defined as the point at which ventilation increases at greater rate than oxygen consumed (VO2.)
Timepoint [2] 332202 0
8 weeks (end intervention)
Secondary outcome [3] 332203 0
Capillary lactate concentration measured by capillary blood samples and analysed using a portable lactate analyser (Lactate Scout+ (EKF Diagnostics)). Concentration is measured in mmol/L.
Capillary blood samples are collected pre-exercise and at 1 min and 5 min post cycle ergometer graded exercise test.
Timepoint [3] 332203 0
8 weeks (end intervention)
Secondary outcome [4] 332204 0
Peak heart rate during cycle ergometer graded exercise test.
Timepoint [4] 332204 0
8 weeks (end intervention)
Secondary outcome [5] 332205 0
Distance walked in 6 minutes (6 minute walk test)
Timepoint [5] 332205 0
8 weeks (end intervention)
Secondary outcome [6] 332206 0
VO2 peak during 6 minute walk test
VO2 (peak) will be measured using a portable wearable metabolic system (Cosmed K5, Italy) during the 6 minute walk test. VO2peak is defined as the highest recorded oxygen consumption during any given 15sec epoch measured in L/min, and mL/kg/min.
Timepoint [6] 332206 0
8 weeks (end intervention)
Secondary outcome [7] 332207 0
Comfortable walking speed over 10m, assessed as time taken to walk the middle 10m of a 14m walkway (time measured using a stopwatch). Participants will be instructed to walk at their comfortable speed.
Timepoint [7] 332207 0
8 weeks (end intervention)
Secondary outcome [8] 332208 0
Weight measured by standard scales.
Timepoint [8] 332208 0
8 weeks (end intervention)
Secondary outcome [9] 332209 0
Quality of life (EQ-5D)
Timepoint [9] 332209 0
8 weeks (end intervention)
Secondary outcome [10] 332210 0
Fugyl-Meyer lower limb assessment
Timepoint [10] 332210 0
8 weeks (end intervention)
Secondary outcome [11] 332211 0
Fatigue (Fatigue assessment scale) measured at rest.
Timepoint [11] 332211 0
8 weeks (end intervention)
Secondary outcome [12] 332212 0
Depression (Hospital Anxiety and Depression Scale)
Timepoint [12] 332212 0
8 weeks (end intervention)
Secondary outcome [13] 332213 0
Accelerometer-derived measures of physical activity
Participants will wear two activity monitors (the thigh-worn activPAL3 and the waist-worn actigraph GT3x+) for 7-days. The specific measures recorded are:
activPAL-derived variables:
Time spent sitting/lying (the monitor does not distinguish between sitting and lying) (min/day)
Time spent standing (min/day)
Time spent walking (min/day)
Step counts (number)
actigraph-derived variables
time in light intensity physical activity (min/day)
time in moderate to vigorous physical activity (min/day)
Timepoint [13] 332213 0
8 weeks (end intervention)
Secondary outcome [14] 332991 0
Respiratory exchange ratio measured by the portable metabolic system (Cosmed K5) during the cycle ergometer graded exercise test.
Respiratory exchange ratio is the ratio of CO2 produced (VCO2) to oxygen consumed (VO2).
Timepoint [14] 332991 0
8 weeks (end intervention)
Secondary outcome [15] 332992 0
Resting heart rate prior to cycle ergometer graded exercise test.
Timepoint [15] 332992 0
8 weeks (end intervention)
Secondary outcome [16] 332993 0
Walking capacity as measured in distance (m) walked in 6 minutes (6 minute walk test).
Timepoint [16] 332993 0
8 weeks (end intervention)
Secondary outcome [17] 332994 0
Fast walking speed over 10 m, assessed as time taken to walk the middle 10m of a 14m walkway (time measured using a stopwatch). Participants will be instructed to walk as fast as they comfortably can.
Timepoint [17] 332994 0
8 weeks (end intervention)
Secondary outcome [18] 332995 0
Waist circumference
Timepoint [18] 332995 0
8 weeks (end intervention)
Secondary outcome [19] 332996 0
Resting blood pressure measured using an automated blood pressure monitor.
Timepoint [19] 332996 0
8 weeks (end intervention)

Eligibility
Key inclusion criteria
Stroke at least 3 months prior
Able to walk with no more than one person assist
Medical clearance to exercise
Internet access at home
Suitable area to exercise at home and availability of responsible person at home to supervise exercise
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Unable to understand instructions in English due to language or cognitive impairments
Pregnant or planning to be pregnant during study period
Self-report current physical activity levels more than 20 minutes/day, 3 days/week
Diagnosed acute or chronic illness with known physical activity contraindications or limits ability to to complete the fitness assessment or intervention
Unable to commit to 10 consecutive weeks of study participation, including attending testing sessions
Current enrolment in other research trial or rehabilitation therapy which focusses on encouraging participation in physical activity.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
A dose-finding design. Cohorts of participants (n=5 per dose) will be given increasingly higher doses of exercise until a pre-defined proportion show an increase in cardiorespiratory fitness above a pre-defined clinically important threshold following an 8-week exercise program.

Dose is defined as the total accumulated exercise time per week, commencing at 30 min.week-1 (3x10min) increasing incrementally per dose by 15min/week (5min per session). The subsequent doses are 45 (3x15), 60 (3x20), 75 (3x25), min.week-1.

Minimum response criteria (MRC). An increase in VO2peak of 2ml.kg-1.min-1. This is the mean change reported in previous studies of stroke survivors and represents an increase of approximately 15%.

Dose limiting threshold (DLT): DLT is reached if participants i) fail to complete more than 50% of the prescribed weekly exercise dose due to factors related to the intervention ii) are unable to exercise for the required session duration iii) withdraw from the study due to injury or illness that can be attributed to the intervention or iv) experience difficulty performing their normal activities of daily living following the exercise dose. The dose limiting threshold must not be reached by more than one third of any cohort.
Phase
Not Applicable
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
The design minimises the numbers of participants treated with both low ineffective doses and high toxic doses. A total sample size of n=20 (5 per dose, 4 successive doses).
Descriptive statistics will be used to assess whether individual participants met the minimum response criteria (increase in VO2peak of at least 2ml.kg-1.min-1) and the dose limiting criteria.
Within participant change in the secondary outcome measures will be assessed descriptive statistics.

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)
NSW

Funding & Sponsors
Funding source category [1] 295765 0
Charities/Societies/Foundations
Name [1] 295765 0
Stroke Foundation of Australia
Address [1] 295765 0
Level 7, 461 Bourke Street Melbourne VIC 3000
Country [1] 295765 0
Australia
Primary sponsor type
University
Name
Univeristy of Newcastle
Address
School of Health Sciences
University Drive
Callaghan, NSW 2308
Country
Australia
Secondary sponsor category [1] 294614 0
None
Name [1] 294614 0
Address [1] 294614 0
Country [1] 294614 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297063 0
Hunter New England Human Research Ethics Committee
Ethics committee address [1] 297063 0
Locked Bag No 1
New Lambton
NSW 2305
Ethics committee country [1] 297063 0
Australia
Date submitted for ethics approval [1] 297063 0
19/10/2016
Approval date [1] 297063 0
14/11/2016
Ethics approval number [1] 297063 0
16/10/19/4.09
Ethics committee name [2] 297067 0
University of Newcastle Human Research Ethics Committee
Ethics committee address [2] 297067 0
NIER Block C
The University of Newcastle
Callaghan
NSW 2308
Ethics committee country [2] 297067 0
Australia
Date submitted for ethics approval [2] 297067 0
17/02/2017
Approval date [2] 297067 0
20/02/2017
Ethics approval number [2] 297067 0
H-2017-0045

Summary
Brief summary
Aim: To determine the minimum dose of exercise required to elicit a positive clinically meaningful improvement in cardiorespiratory fitness in stroke survivors.

Eligible participants are independently- ambulant, community dwelling stroke survivors who have met the screening criteria. Fitness will be assessed pre, during and after an 8-week exercise intervention. Habitual activity (over a 7-day period) will also be assessed at these time points.

Baseline measures include demographics (age, gender, living arrangements), stroke-specific variables (stroke type and severity, time since stroke, side affected, level of disability, anthropometric measures (height, weight, girths), cognitive function and exercise preference.

Intervention
Participants will participate an 8-week 3 day/week home-based individually prescribed exercise program and will be monitored remotely via tele-rehabilitation..

Exercise sessions will consist of 5 minute intervals at alternating higher/lower intensities (55-85% HR max), progressing from 30s/30s to 2min/2min by week 8 as tolerated. Programs will take into account initial fitness level, degree of disability and participant preference. The starting dose duration will be 30 min/week, progressing 15min/week per dose.

The primary outcome will be the smallest dose of exercise required to increase cardiorespiratory fitness by 2ml.kg-1.min-1 in 8 weeks where dose is defined as the total number of minutes of exercise prescribed per week at a moderate to vigorous intensity (55 to 85% HR max).

Secondary measures include blood pressure, weight, girths, cycle GXT peak power output, peak HR, lactate, walking ability, mood (anxiety and depression), physical activity level and health-related quality of life factors (HRQoL).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 72850 0
A/Prof Coralie English
Address 72850 0
School of Health Sciences, University of Newcastle
University Drive
Callaghan
NSW 2308
Country 72850 0
Australia
Phone 72850 0
+61 2 49138102
Fax 72850 0
Email 72850 0
coralie.english@newcastle.edu.au
Contact person for public queries
Name 72851 0
A/Prof Coralie English
Address 72851 0
School of Health Sciences, University of Newcastle
University Drive
Callaghan
NSW 2308
Country 72851 0
Australia
Phone 72851 0
+61 2 49138102
Fax 72851 0
Email 72851 0
coralie.english@newcastle.edu.au
Contact person for scientific queries
Name 72852 0
A/Prof Coralie English
Address 72852 0
School of Health Sciences, University of Newcastle
University Drive
Callaghan
NSW 2308
Country 72852 0
Australia
Phone 72852 0
+61 2 49138102
Fax 72852 0
Email 72852 0
coralie.english@newcastle.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No/undecided IPD sharing reason/comment
What supporting documents are/will be 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