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Trial registered on ANZCTR


Registration number
ACTRN12620000215921
Ethics application status
Approved
Date submitted
5/02/2020
Date registered
24/02/2020
Date last updated
24/02/2020
Date data sharing statement initially provided
24/02/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
DOSE ranging in UPper limb rehabilitation post stroke (DOSE-UP)
Scientific title
DOSE ranging in UPper limb rehabilitation post stroke (DOSE-UP): Phase I trial
Secondary ID [1] 300224 0
None
Universal Trial Number (UTN)
Nil
Trial acronym
DOSE-UP
Linked study record
None

Health condition
Health condition(s) or problem(s) studied:
Stroke 315788 0
Condition category
Condition code
Physical Medicine / Rehabilitation 314076 314076 0 0
Occupational therapy
Physical Medicine / Rehabilitation 314092 314092 0 0
Physiotherapy
Stroke 314093 314093 0 0
Haemorrhagic
Stroke 314094 314094 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
DOSE-UP includes two subgroups within the trial; early in recovery (recruit participants 3 to 14 days post stroke) and late in recovery (recruit participants 3 to 9 months post stroke).

What intervention and why:
The intervention administered during the trial will be a combination of impairment and task-specific, upper limb motor training. An example of an impairment-based exercise would be repetitive practice of wrist extension whereas a task specific exercise would be repetitive practice of reaching for a cup. The rationale for this decision is based on optimal training characteristics from stroke motor learning literature, Australian National Stroke Foundation Guidelines, and previous findings from stroke recovery trials.

Who:
Please refer to Eligibility for details of participants involved in the study. The intervention will be delivered by clinicians (e.g. occupational therapist, physiotherapist, exercise physiologist) with experience and training in the established impairment and task-specific, upper limb motor training protocol.

How:
EARLY - The mode of therapy will be provided face to face in either fully supervised or semi supervised practice.
LATE - The mode of therapy will be provided face to face in either fully supervised or semi supervised practice for four out of the five days per week. The fifth day can be self-directed practice at home, outlined by the study investigator.

Where:
EARLY - The intervention will be conducted at a listed acute, subacute or outpatient site or the participant's home (if applicable).
LATE: The intervention will be conducted at a listed outpatient site or the participant's home (if applicable).
The preference is for all intervention to be conducted at a listed outpatient site. Home based therapy will be considered on a case-by-case basis. The factors contributing to this decision will include, number of other participants on the study, local procedures at listed sites regarding home visiting and location of the participant’s home.

When and how much:
EARLY - The intervention will be delivered within the first month after stroke. The purpose of the trial is to determine the maximum tolerated dose regimen, therefore “how much” therapy a participant will receive is dependent on which cohort they are recruited too. The duration of the intervention period (10 days) and the number of days of treatment per week (5 days) will be consistent across all cohorts. The number of sessions per day and the session intensity will be manipulated, with the starting dose for cohort 1 being 1x15min time on task session per day.
LATE - The intervention will start within the 3 to 9 month window post stroke. The purpose of the trial is to determine the maximum tolerated dose regimen, therefore “how much” therapy a participant will receive is dependent on which cohort they are recruited too. The duration of the intervention period (15 days) and the number of days of treatment per week (5 days) will be consistent across all cohorts. The number of sessions per day and the session intensity will be manipulated, with the starting dose for cohort 1 being 1x30min time on task session per day.

For both subgroups, the maximum dose will be a total of 360 minutes (6 hours) time on task. The number of sessions and session intensity delivered to cohort 2 and beyond will be based on a dose allocation algorithm. The study will escalate on number of sessions per day, followed by time on task.
Intervention code [1] 316497 0
Treatment: Other
Intervention code [2] 316498 0
Rehabilitation
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 322468 0
Maximum tolerated dose regimen of upper limb training post stroke will be identified using a set of pre-specified, dose limiting criteria that are regarded as sufficient to claim a tested dose is not tolerable. The participant will be asked about the reason for session cessation e.g., pain, fatigue, effort or other such as lack of interest. The reason will be recorded and if applicable an appropriate outcome measure will be taken e.g., visual analogue scale.
Timepoint [1] 322468 0
The maximum tolerated dose regimen will be determined at the conclusion of the trial, i.e., when the last recruited participant has completed the intervention.
Secondary outcome [1] 378626 0
Fugl-Meyer Assessment for upper extremity (FMA-UE)
Timepoint [1] 378626 0
EARLY - Baseline and Day 10 of intervention period
LATE - Baseline and Day 15 of intervention period
Secondary outcome [2] 378627 0
Action Research Arm Test (ARAT)
Timepoint [2] 378627 0
EARLY - Baseline and Day 10 of intervention period
LATE - Baseline and Day 15 of intervention period
Secondary outcome [3] 378628 0
Box and Block Test (BBT)
Timepoint [3] 378628 0
EARLY - Baseline and Day 10 of intervention period
LATE - Baseline and Day 15 of intervention period
Secondary outcome [4] 378629 0
Rating of Everyday Arm Use in Community and Home (REACH).
Timepoint [4] 378629 0
EARLY - Baseline and Day 10 of intervention period
LATE - Baseline and Day 15 of intervention period
Secondary outcome [5] 378630 0
Patient Health Questionnaire 9 (PHQ-9).
Timepoint [5] 378630 0
EARLY - Baseline and Day 10 of intervention period
LATE - Baseline and Day 15 of intervention period
Secondary outcome [6] 378631 0
Modified Rankin Scale (mRS).
Timepoint [6] 378631 0
EARLY - Baseline and Day 10 of intervention period
LATE -Baseline and Day 15 of intervention period
Secondary outcome [7] 378632 0
National Institute of Health Stroke Scale (NIHSS).
Timepoint [7] 378632 0
EARLY - Baseline and Day 10 of intervention period
LATE - Baseline and Day 15 of intervention period
Secondary outcome [8] 378633 0
Shoulder abduction and finger extension (SAFE).
Timepoint [8] 378633 0
EARLY - Baseline and Day 10 of intervention period
LATE - Baseline and Day 15 of intervention period
Secondary outcome [9] 378634 0
Visual Analogue Scale - Pain (VAS-Pain).
Timepoint [9] 378634 0
EARLY - Baseline and Day 10 of intervention period
LATE - Baseline and Day 15 of intervention period
Secondary outcome [10] 378635 0
Visual Analogue Scale - Fatigue (VAS - Fatigue).
Timepoint [10] 378635 0
EARLY - Baseline and Day 10 of intervention period
LATE - Baseline and Day 15 of intervention period

Eligibility
Key inclusion criteria
EARLY:
-Current inpatient at time of recruitment,
-Hospital diagnosis of stroke (ischemic or haemorrhagic) confirmed on clinical scanning (CT/MRI),
-Acute to early subacute phase of recovery, between 3 to 14 days post stroke onset,
-Aged 18 years or over,
-Upper limb impairment consistent with manual muscle testing of shoulder abduction and finger extension (SAFE) score of 2 to 7,
-Able to follow basic one stage commands in English,
-Able to provide written informed consent; note, family or authorised representative consent will be sought from individuals with insufficient comprehension to consent, defined by a score > 5 on Short Portable Mental State test, and
-Appropriate candidate for therapy in the home if required.

LATE:
-Discharged from the inpatient hospital setting,
-Diagnosis of stroke (ischemic or haemorrhagic),
-Late subacute phase of recovery, between 3 to 9 months post stroke,
-Aged 18 years or over,
-Upper limb impairment consistent with manual muscle testing of shoulder abduction and finger extension (SAFE) score of 2 – 7,
-Able to follow basic one stage commands in English,
-Able to provide written informed consent; note, family or authorised representative consent will be sought from individuals with insufficient comprehension to consent, defined by a score > 5 on Short Portable Mental State test, and
-Appropriate candidate for therapy in the home if required.
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
EARLY:
-Had a previous stroke(s) with residual deficits at current stroke onset,
-Diagnosis of other neurological conditions (e.g., dementia, Parkinson’s Disease, MS)
-Palliation of comorbid medical illness which in the opinion of the treating neurologist, it is deemed unlikely the patient will be able to actively participate in training,
-Concomitate condition that would interfere with participation (e.g., undergoing radiotherapy),
-Planned discharged to a location other than the community, Melbourne Health, Austin Health and Western Health, or
-Unable to commit to the upper limb training regimen.

LATE:
-Had a previous stroke(s) with residual motor deficits,
-Diagnosis of other neurological conditions (e.g., dementia, Parkinson’s Disease, MS)
-Concomitate condition that would interfere with participation (e.g., undergoing a treatment radiotherapy), or
-Unable to travel and commit to the upper limb training regimen.

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)
N/A
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
N/A
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Other
Other design features
This is a dose ranging trial which adopts a 3 + 5 Phase I Design.
Phase
Phase 1
Type of endpoint(s)
Safety
Statistical methods / analysis
Primary Outcome: Maximum tolerated dose regimen of upper limb training post stroke.
MTDR of upper limb training, will be identified from the dose allocation algorithm at the conclusion of the study, i.e., when the last participant, in the last cohort concludes the intervention period.

Secondary Outcomes:
1. To describe individual dimensions of the multidimensional MTDR in upper limb training post stroke. The individual dimensions will be identified from data extracted participants’ training logs and an exploration of the DLC. This will be summarised using means (standard deviations), median (interquartile range), counts, and proportions as appropriate.
2. To investigate potential efficacy outcomes to inform the design of a future phase II, upper limb stroke recovery trial. Potential efficacy outcomes will be reported as means (standard deviation) or median (interquartile range), for baseline and end of intervention timepoints.

Recruitment
Recruitment status
Not yet 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)
VIC
Recruitment hospital [1] 15595 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [2] 15596 0
Royal Melbourne Hospital - Royal Park campus - Parkville
Recruitment postcode(s) [1] 29212 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 304655 0
University
Name [1] 304655 0
University of Melbourne
Address [1] 304655 0
Department of Physiotherapy
Level 7, Alan Gilbert Building
161 Barry Street,
Carlton, VIC, 3053
Country [1] 304655 0
Australia
Funding source category [2] 304989 0
Hospital
Name [2] 304989 0
Melbourne Health
Address [2] 304989 0
Royal Melbourne Hospital
300 Grattan Street,
Parkville, VIC, 3052
Country [2] 304989 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Office of Research Ethics and Integrity.
Level 5, Alan Gilbert Building (#104)
161 Barry Street, Carlton VIC 3053
Country
Australia
Secondary sponsor category [1] 304959 0
None
Name [1] 304959 0
Address [1] 304959 0
Country [1] 304959 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 305076 0
Melbourne Health Human Research Ethics Committee
Ethics committee address [1] 305076 0
Office of Research
CITY CAMPUS
Level 2
South West
300 Grattan Street
Parkville VIC, 3052
Ethics committee country [1] 305076 0
Australia
Date submitted for ethics approval [1] 305076 0
27/11/2019
Approval date [1] 305076 0
09/01/2020
Ethics approval number [1] 305076 0
HREC/59389/MH-2019

Summary
Brief summary
DOSE-UP will bring us closer to understanding what the optimal dose of upper limb therapy is to maximise recovery. Our project will identify the maximum tolerated dose regimen (MTDR) of upper limb therapy at two different recovery points after stroke. The early in recovery subgroup will recruit participants 3 to 14 days post stroke and late in recovery subgroup will recruit participants 3 to 9 months post stroke. At time of consent, participants will be allocated a dose of therapy to test, and their response will determine the dose to be tested with future participants. We expect this study to provide answers to the question, what is the tolerable dose of upper limb training and support better development of intervention protocols for testing with stroke survivors in clinical trials.
Trial website
N/A
Trial related presentations / publications
N/A
Public notes
N/A

Contacts
Principal investigator
Name 99182 0
Dr Kathryn Hayward
Address 99182 0
University of Melbourne
245 Burgundy Street
Heidelberg, VIC, 3084
Country 99182 0
Australia
Phone 99182 0
+61 401 465 463
Fax 99182 0
Email 99182 0
kate.hayward@unimelb.edu.au
Contact person for public queries
Name 99183 0
Ms Emily Dalton
Address 99183 0
University of Melbourne
245 Burgundy Street
Heidelberg, VIC, 3084
Country 99183 0
Australia
Phone 99183 0
+61 437 240 534
Fax 99183 0
Email 99183 0
daltone@student.unimelb.edu.au
Contact person for scientific queries
Name 99184 0
Ms Emily Dalton
Address 99184 0
University of Melbourne
245 Burgundy Street
Heidelberg, VIC, 3084
Country 99184 0
Australia
Phone 99184 0
+61 437 240 534
Fax 99184 0
Email 99184 0
daltone@student.unimelb.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
What supporting documents are/will be available?
No other documents available
Summary results
No Results