Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12619001423101
Ethics application status
Approved
Date submitted
3/10/2019
Date registered
15/10/2019
Date last updated
18/10/2022
Date data sharing statement initially provided
15/10/2019
Date results information initially provided
18/10/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
Training Intensity Early after Stroke
Scientific title
Phase 1, dose escalating study to determine maximum safe exercise training intensity early after stroke
Secondary ID [1] 297715 0
Nil known
Universal Trial Number (UTN)
U1111-1230-0453
Trial acronym
TIES
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 312028 0
Condition category
Condition code
Stroke 310596 310596 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Physical Fitness Training
The intervention will consist of two components: cardiorespiratory fitness (CRF) training and strength training. The CRF training configuration will be interval training with active rest. The CRF training exercise-rest ratios 1:1 min.

CRF training
The duration of the CRF training component will be 30 minutes (excluding warm-up and cool down). Each session will start with a low intensity warm up and finish with a cool down each lasting about 5 minutes. The mode of CRF training will be interval training with active rest-periods where possible. The exercise modality can be treadmill walking, cycling on an ergometer, overground walking, rowing or exercise on the recumbent stepper and will decided according to the availability of exercise machines and participant’s preference. Participants will attend 3 CRF training sessions per week for a total period of 4 weeks. During the first two weeks, each participant will start with an adaptation period (Phase I) after testing and assessments. In this phase participants will be familiarized with the training procedures and exercises. During Phase I the training intensity which is determined by the percentage of heart rate reserve, will be increased for each bout of exercise within the session or between sessions, based on the individual performance, until the target intensity is reached. This target intensity is predefined and is the same for all participants in the same cohort. The dose will escalate according to a dose-escalation schedule for each following cohort that will be included in the study. The dose intensity will increase with increments of 5% of heart rate reserve. The safety and tolerability of the target intensity will be tested in the last two weeks i.e. Phase II.

Strength training
In addition to the CRF training component participants will also get functional strength training with a frequency of 2 times per week, which will be added on to the first and the last session of the CRF training of the week. Participants will perform three whole body strength exercises. The intensity is based on the pre-training strength tests. The same three exercises will be performed by the same participant for the duration of their involvement in the study. The intensity of strength training will be increased to a max of 4 sets of 12 repetitions. The dose will first increase by adding repetitions to a max of 12 per set. If 12 repetitions are reached than another set will be added and repetitions per set will be set back to 8 per set. If the maximum number of sets and repetitions are reached the resistance will be increased where possible. There are no specific target doses set for the participants in any of the cohorts.

The screening and baseline assessments will be performed at the exercise clinic at the a research institute on the acute hospital campus. The exercise program will take place at different locations depending on the current location of the participants and include the acute hospital, inpatient or outpatient rehabilitation centres or at the research institute. The exercise intervention will be administered by a trained researcher.
Intervention code [1] 313952 0
Rehabilitation
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 321588 0
Safety and tolerability represented by the occurrence of a dose limiting events in a cohort:

Dose limiting events are defined events that represent symptoms of over training, and are the following:
• An increase in pain from baseline, equating to 3 points on the Visual Analogue Scale (VAS) (0-10 cm), that prevents exercise
• Volitional fatigue and cessation of the training session before the scheduled end point.
• Inability to maintain the prescribed training intensity for more than 20% of the dose testing session duration.
• Inability to train for more than 20% of the total dosed sessions due to fatigue or pain (not including the preparation and adaptation sessions).
• Adverse cardiorespiratory events (assessed by HR and BP monotoring during the sessions, and patient self report and in case of serious events i.e. hospital admission clinical record will be checked for verification).



Timepoint [1] 321588 0
During intervention period
Secondary outcome [1] 375497 0
Change is VO2peak will be determined by a graded exercise test using a metabolic cart. assessed using a metabolic cart (Oxycon Mobile). Participants will perform the exercise test on a total body recumbent stepper using the protocol that has been shown to be a valid, safe and feasible measurement of VO2peak in a subacute stroke population.
Timepoint [1] 375497 0
One week after 4 week intervention.

Eligibility
Key inclusion criteria
1) ischaemic stroke diagnosis based on MRI/CT or clinical diagnosis, 2) are within 3 weeks post stroke, 3) have no pre-morbid or current restrictions to exercise, 4) are able to transfer from a sitting position to a standing position either independently or with physical assistance, 5) are able to provide informed consent to participate in the study
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) hospitalization for myocardial infarction, heart surgery, or congestive heart failure during the preceding 3 months; 2) significant cardiac pathology (arrhythmia, hypertrophic cardiomyopathy, severe aortic stenosis, or pulmonary embolus); 3) significant pulmonary pathology (i.e. severe chronic obstructive pulmonary disease) and 4) musculoskeletal or neurological problems from conditions other than stroke that would limit the ability to exercise (e.g. Parkinson’s Disease, severe osteoarthritis).

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)
Not applicable
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Not applicable
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase I 5+5 stratified dose-escalating study design
The safety and tolerability of each pre-defined consecutive intensity of fitness training will be determined in separate cohort of 5 participants in each strata.. The target intensity needs to be reached in at least 80% of the targeted exercise bouts for each session for it to be considered successful achievement of the intensity.
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis
No formal sample size calculations will be performed, given that the number of participants who will complete the training is determined by reaching the stopping criteria for the trial. It is expected that the maximum safe and tolerable dose will range between 60% and 70% of the heart rate reserve, which requires 20-25 participants in each study (i.e. 4-5 cohorts in each study). Descriptive statistics will be used to report characteristics of participants in each cohort including: age, days since stroke, stroke severity, and exercise capacity (VO2peak). The actual training intensity of CRF training reached will be calculated for each participant. The average percentage of HRR in each of the sessions in Phase II, with standard deviations will be calculated for each participant. Additionally, the percentage of bouts at target HRR of all 6 sessions in Phase II will be reported for each participant.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Participant recruitment difficulties
Other reasons/comments
Other reasons
During COVID lockdowns in Melbourne we were unable to recruit patients for this trial over in 2020-2022 as a result our funding ran out and we had no staff available.
Date of first participant enrolment
Anticipated
Actual
25/10/2016
Date of last participant enrolment
Anticipated
30/03/2020
Actual
6/01/2020
Date of last data collection
Anticipated
30/04/2020
Actual
10/03/2020
Sample size
Target
40
Accrual to date
Final
26
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 14926 0
Austin Health - Austin Hospital - Heidelberg
Recruitment postcode(s) [1] 28197 0
3084 - Heidelberg

Funding & Sponsors
Funding source category [1] 302241 0
Government body
Name [1] 302241 0
NHMRC Centre of research excellence Stroke Rehabilitation and Brain Recovery-future leader grant
Country [1] 302241 0
Australia
Funding source category [2] 312462 0
Hospital
Name [2] 312462 0
Austin Medical Research Foundation
Country [2] 312462 0
Australia
Primary sponsor type
Other
Name
The Florey Institute of Neuroscience and Mental Health
Address
30 Royal Parade
Parkville VIC 3052
Australia
Country
Australia
Secondary sponsor category [1] 302095 0
None
Name [1] 302095 0
Address [1] 302095 0
Country [1] 302095 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302918 0
Austin Health Human Research Ethics Committee (HREC)
Ethics committee address [1] 302918 0
Austin Health
145 Studley Road
PO Box 5555
Heidelberg, Victoria 3084
Ethics committee country [1] 302918 0
Australia
Date submitted for ethics approval [1] 302918 0
03/02/2016
Approval date [1] 302918 0
26/05/2016
Ethics approval number [1] 302918 0
HREC/16/Austin/40

Summary
Brief summary
This is a novel dose-escalation study to find the maximum tolerable cardiorespiratory fitness (CRF) training intensity in acute stroke survivors. Small consecutive groups of five stroke survivors receive a CRF training program at a certain intensity. In the next cohort of five participants, the intensity can escalate, stay the same or the study will be stopped and will be based on pre-defined rules. The rules are determined by the occurrence of symptoms of over-exercising in each cohort i.e. increase in pain and exhaustion. If the study is stopped the intensity in the previous cohort of 5 will be regarded as the maximum tolerable training intensity.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 91846 0
Dr Sharon Kramer
Address 91846 0
Melbourne Brain Centre, Austin Campus
Level 1, 245 Burgundy Street
Heidelberg VIC 3084, Australia
Country 91846 0
Australia
Phone 91846 0
+61 390357332
Fax 91846 0
Email 91846 0
[email protected]
Contact person for public queries
Name 91847 0
Dr Sharon Kramer
Address 91847 0
Melbourne Brain Centre, Austin Campus
Level 1, 245 Burgundy Street
Heidelberg VIC 3084, Australia
Country 91847 0
Australia
Phone 91847 0
+61 390357332
Fax 91847 0
Email 91847 0
[email protected]
Contact person for scientific queries
Name 91848 0
Dr Sharon Kramer
Address 91848 0
Melbourne Brain Centre, Austin Campus
Level 1, 245 Burgundy Street
Heidelberg VIC 3084, Australia
Country 91848 0
Australia
Phone 91848 0
+61 390357332
Fax 91848 0
Email 91848 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


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.