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Trial registered on ANZCTR


Registration number
ACTRN12617000469314
Ethics application status
Approved
Date submitted
14/03/2017
Date registered
31/03/2017
Date last updated
23/10/2020
Date data sharing statement initially provided
25/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Do measures of brain activity predict recovery of the ability to communicate after stroke and predict response to speech therapy?
Scientific title
An examination of whether measures of brain function and structure in subacute post-stroke aphasia predict language recovery (naming and comprehension) and word retrieval treatment response at 3 months and 6 months post stroke-onset.
Secondary ID [1] 291239 0
NHMRC - APP1104194
Universal Trial Number (UTN)
Trial acronym
PAPAR
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Aphasia post stroke 302174 0
Condition category
Condition code
Stroke 301783 301783 0 0
Ischaemic
Stroke 302007 302007 0 0
Haemorrhagic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The patient cohort will be randomly assigned to either treatment or a usual care control condition (stratified based on severity of language deficit).

Prior to receiving treatment or usual care, all participants will undertake a neuroimaging scan, including a language-based functional MRI, which will be used as a predictor for language recovery.

Therapy group:
- The therapy provided to participants in the therapy group of the study will include individual word retrieval treatment focused primarily on the phonological (sound) representation
- The word retrieval treatment will be delivered individually at 1 month post-stroke onset (following scanning) by qualified speech pathologists over 3 x 1 hour sessions a week for a period of 8 weeks.
- Stimuli (nouns) will be selected for treatment based on pre-test performance indicating difficulties with naming individual items. 2 sets of items will be selected (matched for relevant psycholinguistic variables), with one set treated and the other untreated to test for generalisation.
- The content of treatment is based on evidence for the effectiveness of word retrieval treatments that include repetition, phonological cueing, and phonological judgments (e.g., Nickels, 2000; Van Hees et al., 2013). In accordance with Leonard et al. (2008) and our work (Van Hees et al., 2013), patients are asked to attempt to name the item. They are then asked to produce the features of the item according to each cue word in a matrix. The cues include: first sound, syllables, last sound, association, and rhyme. If a participant is unable to produce a response, the clinician provides a response both orally and in written form. After all the features are produced, the participant is asked to name the item again. Another component of treatment will involve repetition of the name in the presence of its picture.
- Treatment will also include computer-based therapy (guided by the clinician, approximately 20% of each session), including picture naming for word retrieval, reading aloud for reading comprehension and script practice. Additional activities focused on phrase-level production may be included if impairments are identified (Rodriguez et al., 2013). Homework tasks may also be provided as part of the individualised treatment.
- Patients may receive usual care for other speech and communication impairments.
- Intervention adherence/fidelity will be assessed by recording a sample from a treatment session that will then be reviewed by one of the principal investigators. Strategies used to maintain/improve fidelity will include meetings with research therapists to discuss therapy provision.
Intervention code [1] 297248 0
Rehabilitation
Intervention code [2] 297249 0
Treatment: Other
Comparator / control treatment
Control group:
- 20 healthy age and gender matched controls will be scanned once to identify key regions normally activated in fMRI studies. This data will be critical for determining regions-of-interest and will determine whether normal or novel patterns of activity are observed in patients at each time-point.
- The control participants will also be screened using a brief (5-10 minute) cognitive assessment, the Montreal Cognitive Assessment (MoCA), to rule out cognitive impairment.

Usual Care treatment group:
- The usual care condition will comprise standard speech pathology intervention delivered at the frequency available in each specific health service in which the patient is recruited.
- Frequency and type of usual care intervention may be dependent on setting (e.g., acute hospital, inpatient rehabilitation, outpatient rehabilitation, community based) and will likely be influenced by clinician expertise, and by whether care is delivered in a private or a public health service setting. It may include individual sessions, computer-based therapy, and group sessions.
- Usual care therapy will be documented by the usual care therapists in the various health services, and participants (or their family members) will also keep a diary of therapy activities to assist with data checking by the research team.
- Usual care is unlikely to exceed on average 1-2 sessions of 45 minutes per week.
Control group
Active

Outcomes
Primary outcome [1] 301239 0
Change in naming (Philadelphia Naming Test) at 3 months post stroke onset compared to baseline, as predicted by functional MRI of language-related brain activity at baseline (2-6 weeks post-stroke onset).
Timepoint [1] 301239 0
Baseline (2-6 weeks) to 3 months post stroke onset
Primary outcome [2] 301501 0
Change in comprehension (Comprehensive Aphasia Test) at 3 months post stroke onset compared to baseline, as predicted by functional MRI of language-related brain activity at baseline (2-6 weeks post-onset).
Timepoint [2] 301501 0
Baseline (2-6 weeks) to 3 months post stroke onset
Secondary outcome [1] 332192 0
Change in naming (Philadelphia Naming Test) at 6 months post stroke onset compared to baseline, as predicted by functional MRI of language-related brain activity at baseline (2-6 weeks post-stroke onset).
Timepoint [1] 332192 0
Baseline (2-6 weeks) to 6 months post stroke onset
Secondary outcome [2] 332710 0
Change in comprehension (Comprehensive Aphasia Test) at 6 months post stroke onset compared to baseline, as predicted by functional MRI of language-related brain activity at baseline (2-6 weeks post-stroke onset).
Timepoint [2] 332710 0
Baseline (2-6 weeks) to 6 months post stroke onset
Secondary outcome [3] 332711 0
Change in functional MRI measure of language-related brain activity at baseline (2-6 weeks post-stroke onset) to 3 and 6 months post-stroke onset
Timepoint [3] 332711 0
Baseline (2-6 weeks) to 6 months post stroke onset
Secondary outcome [4] 332712 0
Change in naming (Philadelphia Naming Test) at 3, 6 months post stroke onset compared to baseline.
Timepoint [4] 332712 0
Baseline (2-6 weeks) to 3 and 6 months post stroke onset
Secondary outcome [5] 332713 0
Change in comprehension (Comprehensive Aphasia Test) at 3, 6 months post stroke onset compared to baseline.
Timepoint [5] 332713 0
Baseline (2-6 weeks) to 3 and 6 months post stroke onset
Secondary outcome [6] 332714 0
Change in Western Aphasia Battery - Revised Aphasia Quotient at 3 months and 6 months post stroke onset compared to baseline
Timepoint [6] 332714 0
3 and 6 months post stroke onset
Secondary outcome [7] 332715 0
Change in Pyramids and Palm Trees Test at 3 and 6 months post-stroke onset
Timepoint [7] 332715 0
3 and 6 months post stroke onset
Secondary outcome [8] 333098 0
Changes in connected speech at 3 and 6 months post-stroke onset (based on picture description and the Nicholas and Brookshire procedure, and the Sentence Production Test).
Timepoint [8] 333098 0
3 and 6 months post stroke onset
Secondary outcome [9] 333099 0
Changes in sentence production at 3 and 6 months post-stroke onset (based on picture description and the Nicholas and Brookshire procedure
Timepoint [9] 333099 0
3 and 6 months post stroke onset
Secondary outcome [10] 333102 0
Change in naming (Philadelphia Naming Test) at 3 and 6 months post stroke onset compared to baseline, as predicted by lesion location (based on high resolution structural T1 MRI scan and voxel-based lesion symptom mapping) and white matter tract integrity (based on diffusion imaging measures of generalised fractional anisotropy including arcuate fasciculus).
Timepoint [10] 333102 0
3 and 6 months post stroke onset
Secondary outcome [11] 333103 0
Change in comprehension (Comprehensive Aphasia Test) at 3 and 6 months post stroke onset compared to baseline, as predicted by lesion location (based on high resolution structural T1 MRI scan and voxel-based lesion symptom mapping) and white matter tract integrity (based on diffusion imaging measures of generalised fractional anisotropy including arcuate fasciculus).
Timepoint [11] 333103 0
3 and 6 months post stroke onset
Secondary outcome [12] 333104 0
Change in naming (Philadelphia Naming Test) at 3 and 6 months post stroke onset compared to baseline as predicted by measures of cognition (RBANS verbal memory, Raven's progressive matrices, Test of Everyday Attention, Trail Making A & B).
Timepoint [12] 333104 0
3 and 6 months post stroke onset
Secondary outcome [13] 333105 0
Change in comprehension (Comprehensive Aphasia Test) at 3 and 6 months post stroke onset compared to baseline as predicted by measures of cognition (RBANS verbal memory, Raven's progressive matrices, Test of Everyday Attention, Trail Making A & B).
Timepoint [13] 333105 0
3 and 6 months post stroke onset
Secondary outcome [14] 352979 0
Changes in mood at 3, 6 months post stroke onset compared to baseline (Stroke and Aphasia Quality of Life Scale).
Timepoint [14] 352979 0
Baseline (2-4 weeks) to 6 months post-stroke onset.
Secondary outcome [15] 352980 0
Changes in language processing at 3, 6 months post stroke onset compared to baseline (based on Psycholinguistic Assessments of Language Processing in Aphasia subtests 5, 7, 8, 14, 15 and 27).
Timepoint [15] 352980 0
Baseline (2-4 weeks) to 6 months post-stroke onset.

Eligibility
Key inclusion criteria
People with aphasia:
- Single, first, left hemisphere stroke (as confirmed by CT/MRI) and speech and language impairment as identified by a speech pathologist or other relevant medical, nursing or allied health staff
-Below the aphasia cut-off (93.8 AQ) on the Western Aphasia Battery - Revised (WAB-R) or asphasia (including high level language deficits) as identified by a speech pathologist or other relevant medical, nursing or allied health staff
- MRI compatibility, and able to complete behavioural battery between 2 and 6 weeks post-stroke
- Have sufficient vision and hearing to complete the imaging and behavioural tasks
- Medically stable and able to attend and participate in a therapy program (8 weeks)
- English as a primary language prior to stroke

Control Group:
- healthy older adults matched for age and gender.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
People with aphasia:
- Any other neurological disease or disorder, mental illness, head trauma, alcoholism, cerebral tumour or abscess.
- Any metals present in the body or other contraindications for MRI including claustrophobia.
- Current diagnosis of major clinical depression or other mental health condition that may affect participation.
- Severe dysarthria or apraxia of speech as determined by a speech pathologist.
- Severe auditory comprehension deficits as determined by the WAB-R which would preclude following directions for the scan.
- Substance abuse or dependence in the last 12 months.

Healthy controls:
- Any brain/neurological disorder, mental illness, head trauma, alcoholism and cerebral tumour
- Any contraindications for MRI – claustrophobia or metals in the body e.g., pacemaker, heart valve, dental bridge metal mesh implants/clips/wire sutures, hearing implant etc.

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)
Once meeting eligibility requirements for the study, participants will be randomised to either treatment group or usual care group by a computer code run by an independent, off-site researcher.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Covariate adaptive random allocation will be employed, using the covariates of WAB-AQ severity level (mild 93.7-66; moderate: 65-33; severe: 32-0).
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
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
A series of regression analyses will be run using the contrast estimates from the second level fMRI analysis in the aphasia group as independent variable predictors of the dependent variable of language recovery (naming, comprehension). Language performance dependent variables in this imaging analysis will be considered in terms of outcome (3 and 6 month performance) and percent of maximal achievable recovery . These same scores will be calculated for secondary outcome measures. Other factors of potential importance (e.g. age, lesion size) will be entered into the regression analyses. fMRI region of interest analyses will also be conducted based on healthy control performance and, based on our pilot data.

Recruitment
Recruitment status
Suspended
Date of first participant enrolment
Anticipated
6/04/2017
Actual
27/07/2017
Date of last participant enrolment
Anticipated
31/12/2021
Actual
24/02/2020
Date of last data collection
Anticipated
30/06/2022
Actual
Sample size
Target
115
Accrual to date
11
Final
Recruitment in Australia
Recruitment state(s)
QLD
Recruitment hospital [1] 7661 0
Royal Brisbane & Womens Hospital - Herston
Recruitment hospital [2] 7662 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 7663 0
The Prince Charles Hospital - Chermside
Recruitment hospital [4] 7664 0
Queen Elizabeth II Jubilee Hospital - Coopers Plains
Recruitment hospital [5] 7665 0
The Wesley Hospital - Auchenflower
Recruitment hospital [6] 7666 0
St Andrew's War Memorial Hospital - Brisbane
Recruitment hospital [7] 7667 0
Greenslopes Private Hospital - Greenslopes
Recruitment hospital [8] 7675 0
Redland Hospital - Cleveland
Recruitment hospital [9] 12190 0
Logan Hospital - Meadowbrook
Recruitment hospital [10] 12191 0
Redcliffe Hospital - Redcliffe
Recruitment postcode(s) [1] 15580 0
4029 - Herston
Recruitment postcode(s) [2] 15581 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 15582 0
4032 - Chermside
Recruitment postcode(s) [4] 15583 0
4108 - Coopers Plains
Recruitment postcode(s) [5] 15584 0
4066 - Auchenflower
Recruitment postcode(s) [6] 15585 0
4000 - Brisbane
Recruitment postcode(s) [7] 15586 0
4120 - Greenslopes
Recruitment postcode(s) [8] 15593 0
4163 - Cleveland
Recruitment postcode(s) [9] 24361 0
4131 - Meadowbrook
Recruitment postcode(s) [10] 24362 0
4020 - Redcliffe
Recruitment postcode(s) [11] 24363 0
4114 - Logan City

Funding & Sponsors
Funding source category [1] 295691 0
Government body
Name [1] 295691 0
National Health and Medical Research Council (NHMRC)
Country [1] 295691 0
Australia
Primary sponsor type
Individual
Name
Professor David Copland
Address
UQ Centre for Clinical Research
Faculty of Medicine
Level 3, Building 71/918, Herston
The University of Queensland 4029
Country
Australia
Secondary sponsor category [1] 294583 0
None
Name [1] 294583 0
Address [1] 294583 0
Country [1] 294583 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 297000 0
Royal Brisbane & Women's Hospital HREC
Ethics committee address [1] 297000 0
Ethics committee country [1] 297000 0
Australia
Date submitted for ethics approval [1] 297000 0
22/07/2016
Approval date [1] 297000 0
15/09/2016
Ethics approval number [1] 297000 0
HREC/16/QRBW/376

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

Contacts
Principal investigator
Name 72670 0
Prof David Copland
Address 72670 0
UQ Centre for Clinical Research
Faculty of Medicine
Level 3, Building 71/918, Herston
The University of Queensland 4029
Country 72670 0
Australia
Phone 72670 0
+61 7 3346 5539
Fax 72670 0
Email 72670 0
d.copland@uq.edu.au
Contact person for public queries
Name 72671 0
Tracy Roxbury
Address 72671 0
UQ Centre for Clinical Research
Faculty of Medicine
Level 3, Building 71/918, Herston
The University of Queensland 4029
Country 72671 0
Australia
Phone 72671 0
+61 7 3346 6110
Fax 72671 0
Email 72671 0
PAPAR@cai.uq.edu.au
Contact person for scientific queries
Name 72672 0
David Copland
Address 72672 0
UQ Centre for Clinical Research
Faculty of Medicine
Level 3, Building 71/918, Herston
The University of Queensland 4029
Country 72672 0
Australia
Phone 72672 0
+61 7 3346 5539
Fax 72672 0
Email 72672 0
d.copland@uq.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified MRI scans and behavioural data
When will data be available (start and end dates)?
End 2020-2022
Available to whom?
Collaborators at NHMRC CRE n Aphasia (non-trial personnel; PI Copland is co-director) who have HREC approval to use the collected data for different projects.
Available for what types of analyses?
Analysis of predictors of aphasia recovery
How or where can data be obtained?
Data only available to staff associated with CRE subject to approval by Prof David Copland (PI - d.copland@uq.edu.au)


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.