Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000373774
Ethics application status
Approved
Date submitted
14/02/2022
Date registered
3/03/2022
Date last updated
8/03/2023
Date data sharing statement initially provided
3/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
A trial of integrated arm and language rehabilitation in people living in the community with arm and communication impairments 3 to 24 months post stroke.
Scientific title
A phase IIa multicentre umbrella trial of the efficacy and safety of integrated UPper limb and Language Impairment and Functional Training (UPLIFT) in people 3 to 24 months post stroke
Secondary ID [1] 305896 0
Protocol Number: 001-22
Universal Trial Number (UTN)
U1111-1271-5682
Trial acronym
UPLIFT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Stroke 324453 0
Condition category
Condition code
Stroke 321940 321940 0 0
Ischaemic
Stroke 321941 321941 0 0
Haemorrhagic
Physical Medicine / Rehabilitation 321969 321969 0 0
Physiotherapy
Physical Medicine / Rehabilitation 321970 321970 0 0
Speech therapy
Physical Medicine / Rehabilitation 321971 321971 0 0
Occupational therapy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A 4 week intervention program involving intensive daily training sessions (5 days per week for 2 or 4 hours/day), either in person or via telehealth, incorporating both upper limb (arm) training and language (communication) training. Participants will be randomly allocated to one of four intervention groups, depending upon their degree of stroke-related disability.

Participants shall be assessed to determine their baseline severity of impairment, then assigned to either:
-telerehabilitation at home (if both arm and communication impairments are mild or moderate severity), or
- in-person intervention in the clinic (if at least one of arm or communication impairment is severe).

Participants will subsequently be stratified by time post stroke (either 3-12 months or 12-24months), then randomised to either 2 or 4 hours of intervention/day for 4
weeks.

Upper limb training will focus on impairment and functional training of the arm and hand.
Impairment training will target strength, control, coordination and flexibility. Functional training
will target reaching, grasping, manipulating and releasing an object to maximise function and transition to use in real-world tasks. For people with severe impairment, electrical stimulation will be used to make practice possible.

Language training will target both language impairment and everyday communication in
context.Training will target deficits at the word, sentence, and conversational level in
comprehension and production. Communication in context will focus on communicative
effectiveness in relevant everyday situations through multiple modalities (ie, gestures, speech,
writing).

All training will be delivered one-on-one by qualified Physiotherapists, Occupational Therapists, Speech Pathologists and Allied Health Assistants that have undergone study specific training.

To monitor adherence to the intervention, for each training session, a detailed record of dose and intervention content will be recorded.
Intervention code [1] 322290 0
Rehabilitation
Comparator / control treatment
No control group. Four different models of arm and language training varying in delivery method (in person or via telehealth) and duration (2 or 4 hours/day) will be trialled to identify the most promising approach.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 329697 0
A single binary composite primary outcome, where good outcome is defined by achieving ALL of:

A) Binary outcome: Improvement at or beyond the predefined outcome-specific threshold on at least ONE priority outcome
B) Binary outcome: No deterioration on ANY priority outcome beyond the predefined threshold
C) Binary outcome: Greater than or equal to 75% 'time on task' of the allocated dose target across intervention administration phase
D) Binary outcome: No serious adverse event related to the intervention

The set of priority outcomes (corresponding predefined priority outcome-specific thresholds) are:
1. Fugl Meyer Upper Limb impairment scale (improvement greater than or equal to 5.25 points);
2. Box and Block Test of upper limb activity test (improvement greater than or equal to 5.5 blocks);
3. Western Aphasia Battery for language impairment scale (Aphasia Quotient, AQ) (improvement greater than or equal to 5 points);
4. Communicative Effectiveness Index scale (improvement greater than or equal to 10.37 points)
Timepoint [1] 329697 0
Assessed at Baseline and within 5 days (+/- 2 days) of completion of the 4 week intervention period
Secondary outcome [1] 403492 0
Upper limb function measured using the 9 Hole Peg Test and Action Research Arm test
Timepoint [1] 403492 0
Assessed at Baseline and within 5 days (+/- 2 days) of completion of the 4 week intervention period
Secondary outcome [2] 403493 0
Upper limb participation measured using the Rating of Everyday Arm Use in the Community
and Home (REACH scale)
Timepoint [2] 403493 0
Assessed at Baseline, Week 1, Week 2, Week3, Week 4 and within 5 days (+/- 2 days) of completion of the 4 week intervention period
Secondary outcome [3] 403494 0
Language impairment of naming measured using the Boston Naming Test (BNT)
Timepoint [3] 403494 0
Assessed at Baseline, and within 5 days (+/- 2 days) of completion of the 4 week intervention period
Secondary outcome [4] 403495 0
Discourse video sample of language function
Timepoint [4] 403495 0
Assessed at Baseline, and within 5 days (+/- 2 days) of completion of the 4 week intervention period
Secondary outcome [5] 403496 0
Cognition using Trails A and B, as well as Clock Drawing Task (CLOX). This will be assessed as a composite outcome.
Timepoint [5] 403496 0
Assessed at Baseline, and within 5 days (+/- 2 days) of completion of the 4 week intervention period
Secondary outcome [6] 403497 0
Quality of Life using the Stroke and Aphasia Quality of Life Scale-39 (SAQoL-39)
Timepoint [6] 403497 0
Assessed at Baseline, and within 5 days (+/- 2 days) of completion of the 4 week intervention period
Secondary outcome [7] 403498 0
Disability using the modified Rankin Scale (mRS) will document dependence
Timepoint [7] 403498 0
Assessed at Baseline, and within 5 days (+/- 2 days) of completion of the 4 week intervention period
Secondary outcome [8] 403499 0
Adverse events occurring during the intervention period and documented by the clinician using a study-specific form, will be classified as serious or not, intervention-related, or stroke-related.
Timepoint [8] 403499 0
Assessed throughout the entire intervention period at Week 1, Week 2, Week 3 and Week 4, with reporting complete within 5 days (+/- 2 days) of completion of the 4 week intervention period
Secondary outcome [9] 406395 0
Reaching ability video sample
Timepoint [9] 406395 0
Assessed at Baseline, and within 5 days (+/- 2 days) of completion of the 4 week intervention period

Eligibility
Key inclusion criteria
People with stroke will be screened against the following inclusion criteria:
• Adults greater than or equal to 18 years with a clinical diagnosis of hemispheric stroke (ischaemic/haemorrhagic) between 3 to 24 months prior to recruitment
• First stroke, or if repeat stroke, no residual arm or language deficit from prior stroke(s)
• Presence of upper limb impairment (at minimum, must have at least a flicker of movement somewhere) and language impairment (aphasia; at minimum, must have at least single interpretable word output) after stroke
• Appropriate candidate for therapy in the home if required, and willingness to use the required technology (or assistance available at home to help)
• Able to follow single stage commands, provide informed consent, or medical decision maker can if required
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
People will be excluded if they have:
• Baseline scores that prevent achieving required change on at least one priority outcome
• No residual upper limb and language deficits from a previous stroke
• Severe comorbid medical illness, neurological condition, psychiatric illness or other medical diagnosis deemed by the investigator to make a participant unlikely to be able to fully participate in all study procedures including attendance at a site for baseline and post-intervention assessments
• Life expectancy less than 3 months

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)
Randomisation using a centralised allocation system will ensure balanced assignment to achieve sequential balance, not to enable statistical inference of comparative effect. In the event of internet failure, telephone back up for randomisation allocation will be available. Baseline assessment details including level of disability are entered in the electronic Case Report Form (eCRF), and participants are then randomised to either 2 or 4 hours of training per day.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation stratified by time post stroke and severity of disability using a randomisation table generated via computer software within our online electronic Case Report form (eCRF) in REDCap will be used.

Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Umbrella design with four independent single arm Bayesian Optimal Phase IIa trials.
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
The study is a Phase IIa umbrella trial of integrated UPper limb and Language Impairment and Functional Training (UPLIFT) for stroke survivors living in the community. It is planned that up to 160 adult participants will be recruited across approximately 8 urban and regional hubs in Australia. Within this umbrella trial, simultaneous Bayesian Optimal Phase IIa (BOP) studies will be run to evaluate individual UPLIFT interventions. For each intervention, the rate of promising response (composite good outcome) will be monitored at equally spaced, predefined stopping points. Too few promising responses will mean an individual UPLIFT intervention is stopped and future trial participants are directed into other intervention strata under investigation.

While this umbrella trial is Bayesian in nature, its design ensures appropriate frequentist characteristics, such as power of 0.8 and alpha of 0.05. The sample size was estimated using an online tool for Bayesian Optimal Phase II (BOP) design. Allowing for three equally spaced interim stopping points (n=10, n=20, n=30) and a final decision point analysis (n=40), the sample size of 40 participants per strata was estimated using the null hypothesis rate of upper limb and language recovery of 0.5 vs alternative hypothesis rate of recovery of 0.7.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
7/03/2022
Actual
24/05/2022
Date of last participant enrolment
Anticipated
25/01/2024
Actual
Date of last data collection
Anticipated
29/02/2024
Actual
Sample size
Target
160
Accrual to date
11
Final
Recruitment in Australia
Recruitment state(s)
QLD,SA,WA,VIC
Recruitment hospital [1] 21219 0
Austin Health - Austin Hospital - Heidelberg
Recruitment hospital [2] 21220 0
Royal Melbourne Hospital - City campus - Parkville
Recruitment hospital [3] 21221 0
Surgical Treatment and Rehabilitation Service (STARS) - Herston
Recruitment hospital [4] 21222 0
Townsville University Hospital - Douglas
Recruitment hospital [5] 21223 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [6] 21224 0
The Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 21279 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [8] 21722 0
The University of Melbourne - Parkville
Recruitment hospital [9] 21723 0
James Cook University - Smithfield
Recruitment hospital [10] 21724 0
Edith Cowan University - Joondalup
Recruitment hospital [11] 21725 0
University of Queensland - St Lucia
Recruitment hospital [12] 24220 0
Perron Institute for Neurological and Translational Science - Nedlands
Recruitment postcode(s) [1] 36088 0
3084 - Heidelberg
Recruitment postcode(s) [2] 36089 0
3050 - Parkville
Recruitment postcode(s) [3] 36090 0
4029 - Herston
Recruitment postcode(s) [4] 36091 0
4814 - Douglas
Recruitment postcode(s) [5] 36092 0
6009 - Nedlands
Recruitment postcode(s) [6] 36093 0
5000 - Adelaide
Recruitment postcode(s) [7] 36148 0
4029 - Royal Brisbane Hospital
Recruitment postcode(s) [8] 36772 0
4878 - Smithfield
Recruitment postcode(s) [9] 36773 0
6027 - Joondalup
Recruitment postcode(s) [10] 36774 0
4072 - St Lucia
Recruitment postcode(s) [11] 36775 0
3010 - University Of Melbourne
Recruitment postcode(s) [12] 36776 0
4072 - University Of Queensland

Funding & Sponsors
Funding source category [1] 310244 0
Government body
Name [1] 310244 0
NHMRC Medical Research Future Fund
Country [1] 310244 0
Australia
Primary sponsor type
University
Name
University of Melbourne
Address
Grattan Street
Parkville VIC 3001
Country
Australia
Secondary sponsor category [1] 311994 0
None
Name [1] 311994 0
None
Address [1] 311994 0
Country [1] 311994 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309923 0
Royal Melbourne Hospital Human Research Ethics Committee
Ethics committee address [1] 309923 0
Office for Research
City Campus
Level 2 South West
300 Grattan Street
Parkville Victoria
Ethics committee country [1] 309923 0
Australia
Date submitted for ethics approval [1] 309923 0
22/11/2021
Approval date [1] 309923 0
20/12/2021
Ethics approval number [1] 309923 0

Summary
Brief summary
A large proportion of stroke survivors experience loss of arm and communication functions at 3 months post-stroke. These effects are extremely debilitating and can result in long term disability. The aim of this study is to identify the most promising model of arm and communication rehabilitation for people 3 to 24 months after stroke who are living in the community. It is hypothesised that at least one promising UPLIFT model of rehabilitation combining upper limb and language rehabilitation can be identified and taken forward to further clinical trials and translation into the clinic. Participants shall complete some baseline assessments to determine their level of disability, then undertake a 4 week intervention program. The intervention will be intensive daily training (2 or 4 hours/day), either in person or via telerehabilitation, involving both arm training and communication training. Rehabilitation focuses on combining impairment and functional training for tasks such as reaching to pick up a cup of coffee, with contextual everyday communication such as asking for a cup of coffee, and integration of the two, i.e. reaching to pick up a cup of coffee and saying ‘thank you’ while doing it. Baseline assessments will be repeated at the conclusion of the 4 week intervention period. Participants shall be closely monitored for adverse events throughout the intervention program.
Trial website
https://www.stroke-repair.com/uplift-trial
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 115850 0
Dr Kate Hayward
Address 115850 0
School of Health Sciences
University of Melbourne
Grattan Street
PARKVILLE VIC 3001
Country 115850 0
Australia
Phone 115850 0
+61 3 9035 7293
Fax 115850 0
Email 115850 0
[email protected]
Contact person for public queries
Name 115851 0
Dr Kate Hayward
Address 115851 0
School of Health Sciences
University of Melbourne
Grattan Street
PARKVILLE VIC 3001
Country 115851 0
Australia
Phone 115851 0
+61 3 9035 7293
Fax 115851 0
Email 115851 0
[email protected]
Contact person for scientific queries
Name 115852 0
Dr Kate Hayward
Address 115852 0
School of Health Sciences
University of Melbourne
Grattan Street
PARKVILLE VIC 3001
Country 115852 0
Australia
Phone 115852 0
+61 3 9035 7293
Fax 115852 0
Email 115852 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
Group data will be made publicly available


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.