The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12619000986178
Ethics application status
Approved
Date submitted
28/05/2019
Date registered
11/07/2019
Date last updated
11/07/2019
Date data sharing statement initially provided
11/07/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
The Assessment of Fluoxetine in Stroke Recovery Imaging and Blood Biomarkers Sub - Study AFFINITY BM
Scientific title
The Assessment of Fluoxetine in Stroke Recovery Imaging and Blood Biomarkers Sub - Study AFFINITY BM
Secondary ID [1] 296896 0
nil known
Universal Trial Number (UTN)
Nil Known
Trial acronym
Nil
Linked study record
Sub Study of the The Assessment of Fluoxetine in Stroke Recovery [ The AFFINITY Trial ACTRN 12611000774921]

Health condition
Health condition(s) or problem(s) studied:
stroke 312121 0
Condition category
Condition code
Neurological 310674 310674 0 0
Other neurological disorders
Stroke 311636 311636 0 0
Ischaemic
Stroke 311637 311637 0 0
Haemorrhagic

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Blood sample collection for DNA which can be collected at any of the main AFFINITY trial assessment points [Baseline/Randomisation, Day 28, Day 90, Day 180, Day 365 Visits]
2 x MRI scans. The first scan is collected at Baseline/Randomisation and the second at the Day 180 Assessment Visit for the main AFFINITY Trial. All Main trial follow up continues as per protocol.
Intervention code [1] 314012 0
Not applicable
Comparator / control treatment
none
Control group
Uncontrolled

Outcomes
Primary outcome [1] 319519 0
To determine if random allocation to fluoxetine is associated with activation in the ipsilesional primary motor and medial-premotor cortices [composite primary outcomes] as measured by task-related functional magnetic resonance imaging at 6 months after randomisation, compared with placebo.
Timepoint [1] 319519 0
6 months
Primary outcome [2] 319520 0
Exploratory Outcome: if genetic biomarkers [not yet determined] are associated with greater motor recovery in stroke patients randomly allocated to fluoxetine for 6 months as compared to placebo. To be ascertained from DNA testing.
Note: Motor and functional recovery will be ascertained by linkage to the main AFFINITY Trial Primary Outcome assessments results (Modified Rankin Scale score at 6 month)
Timepoint [2] 319520 0
6 months
Primary outcome [3] 320515 0
Exploratory Outcome: if specific biochemical biomarkers [not yet determined] are associated with greater motor recovery in stroke patients randomly allocated to fluoxetine for 6 months as compared to placebo. To be ascertained from Serum Assay.
Note: Motor and functional recovery will be ascertained by linkage to the main AFFINITY Trial Primary Outcome assessments results (Modified Rankin Scale score at 6 month)
Timepoint [3] 320515 0
6 months
Secondary outcome [1] 368563 0
To determine at 6 months post-randomisation if allocation to fluoxetine vs placebo is associated with evidence of:interhemispheric connectivity of sensorimotor cortices.

Each outcome will be assessed using MRI scan determined by clinician and analysed using a statistical package such as SPM or Freesurfer, as appropriate.







Timepoint [1] 368563 0
6 months
Secondary outcome [2] 371666 0
To determine at 6 months post-randomisation if allocation to fluoxetine vs placebo causes disruption of functional connectivity of depression related brain networks including the thalamus.
Each outcome will be assessed using MRI scan determined by clinician and analysed using a statistical package such as SPM or Freesurfer, as appropriate.
Timepoint [2] 371666 0
6 months
Secondary outcome [3] 371667 0
To determine at 6 months post-randomisation if allocation to fluoxetine vs placebo leads to greater volume and thickness of grey matter (cortical thickness) in the ipsilesional primary motor cortex.
Assessed using MRI scan determined by clinician and analysed using a statistical package such as SPM or Freesurfer, as appropriate.
Timepoint [3] 371667 0
6 Months
Secondary outcome [4] 371668 0
To determine at 6 months post-randomisation if allocation to fluoxetine vs placebo leads to reduced volume of the qualifying stroke lesion
Assessed using MRI scan determined by clinician and analysed using a statistical package such as SPM or Freesurfer, as appropriate.

Timepoint [4] 371668 0
6 Months
Secondary outcome [5] 371669 0
To determine at 6 months post-randomisation if allocation to fluoxetine vs placebo leads to white matter microstructural integrity.
Assessed using MRI scan determined by clinician and analysed using a statistical package such as SPM or Freesurfer, as appropriate.
Timepoint [5] 371669 0
6 Months
Secondary outcome [6] 371885 0
To determine at 6 months post-randomisation if allocation to fluoxetine vs placebo leads to greater volume and thickness of grey matter (cortical thickness) in the ipsilesional primary motor amygdala.
Assessed using MRI scan determined by clinician and analysed using a statistical package such as SPM or Freesurfer, as appropriate.
Timepoint [6] 371885 0
6 months
Secondary outcome [7] 371886 0
To determine at 6 months post-randomisation if allocation to fluoxetine vs placebo leads to greater volume and thickness of grey matter (cortical thickness) in the ipsilesional primary motor hippocampus
Assessed using MRI scan determined by clinician and analysed using a statistical package such as SPM or Freesurfer, as appropriate.
Timepoint [7] 371886 0
6 months
Secondary outcome [8] 372311 0
Exploratory Primary Outcome: if genetic biomarkers [not yet determined] are associated with greater functional recovery in stroke patients randomly allocated to fluoxetine for 6 months as compared to placebo. To be ascertained from DNA testing.
Note: Motor and functional recovery will be ascertained by linkage to the main AFFINITY Trial Primary Outcome assessments results (Modified Rankin Scale score at 6 month)
Timepoint [8] 372311 0
6 months
Secondary outcome [9] 372312 0
Exploratory Outcome: if specific biochemical biomarkers [not yet determined] are associated with greater functional recovery in stroke patients randomly allocated to fluoxetine for 6 months as compared to placebo. To be ascertained from Serum Assay.
Note: Motor and functional recovery will be ascertained by linkage to the main AFFINITY Trial Primary Outcome assessments results (Modified Rankin Scale score at 6 month)
Timepoint [9] 372312 0
6 months
Secondary outcome [10] 372313 0
To determine at 6 months post-randomisation if allocation to fluoxetine vs placebo leads to connectivity of white matter tracts.
Assessed using MRI scan determined by clinician and analysed using a statistical package such as SPM or Freesurfer, as appropriate.
Timepoint [10] 372313 0
6 months

Eligibility
Key inclusion criteria
Participants may partake of either one or both of the sub studies

Inclusion criteria: Blood Biomarkers sub study:
Participants randomised and participating in the AFFINITY Trial

Inclusion criteria: MRI neuroimaging sub study:
Participants randomised and participating in the AFFINITY Trial
Brain imaging consistent with an ischaemic stroke of either hemisphere
Brain imaging conducted within 21 days of qualifying stroke event
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria: MRI neuroimaging sub study:
Brain imaging consistent with haemorrhagic (intracerebral and / or subarachnoid) stroke
Contra-indication to having a MRI e.g. implanted pacemaker or severe claustrophobia (these people can still participate in the blood biomarker sub-study)
Unable to undergo follow up MRI at six months

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Statistical methods
We will analyse and store the data using reliable statistical software (STATA). Baseline data will be compared using descriptive statistics, Student t tests for normally distributed continuous variables, Mann-Whitney test for skewed variables and Pearson’s chi-square statistic for categorical variables.
MRI analyses
Regional grey matter volume differences will be assessed though voxel-based morphometry (VBM) using SPM12. Significant effects will be assessed using a family-wise error (FWE) threshold of p < 0.05, corrected for multiple comparisons. Age, gender, stroke lesion size and intracranial volume will be included as nuisance covariates in the models. Functional MRI data will be analysed with SPM12 utilising appropriate toolkits and we will use Stroketool software (http://www.digitalimagesolutions.de/) to assess lesion size.

Recruitment
Recruitment status
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,QLD,WA
Recruitment hospital [1] 13464 0
Sir Charles Gairdner Hospital - Nedlands
Recruitment hospital [2] 13465 0
Fiona Stanley Hospital - Murdoch
Recruitment hospital [3] 13566 0
Redcliffe Hospital - Redcliffe
Recruitment postcode(s) [1] 26073 0
6009 - Nedlands
Recruitment postcode(s) [2] 26074 0
6150 - Murdoch
Recruitment postcode(s) [3] 26212 0
4020 - Redcliffe
Recruitment outside Australia
Country [1] 21363 0
Viet Nam
State/province [1] 21363 0
Ho Chi Minh City, Hanoi and Thanh Hoa Province

Funding & Sponsors
Funding source category [1] 301467 0
Government body
Name [1] 301467 0
National Health and Medical Research Council - Program Grant
Address [1] 301467 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 301467 0
Australia
Primary sponsor type
Hospital
Name
Sir Charles Gairdner Hospital
Address
Hospital Avenue
Nedlands
Perth, WA
6009
Country
Australia
Secondary sponsor category [1] 302947 0
None
Name [1] 302947 0
Address [1] 302947 0
Country [1] 302947 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 302206 0
Royal Perth Hospital Ethics Committee
Ethics committee address [1] 302206 0
Ethics Committee
Level Five Kirkman House
Royal Perth Hospital
Murray Street

WA 6000



Perth WA
Ethics committee country [1] 302206 0
Australia
Date submitted for ethics approval [1] 302206 0
01/01/2016
Approval date [1] 302206 0
05/03/2019
Ethics approval number [1] 302206 0
Ethics committee name [2] 303090 0
WSLHD Human Research Ethics Committee
Ethics committee address [2] 303090 0
Research Office, Level 2, REN Building
Westmead Hospital, Hawkesbury & Darcy Roads, Westmead
NSW 2145
Ethics committee country [2] 303090 0
Australia
Date submitted for ethics approval [2] 303090 0
31/05/2016
Approval date [2] 303090 0
07/09/2016
Ethics approval number [2] 303090 0
REC/16/WMEAD/127

Summary
Brief summary
The main AFFINITY trial is investigating whether fluoxetine, 20mg once daily, started 2 -15 days after stroke onset and continued for 6 months, improves functional outcome at 6 months after randomisation. The aims of the sub study (AFFINITY BM) are to further investigate the underlying biological, structural and functional mechanisms by which treatment with fluoxetine may lead to improved functional outcomes following acute stroke.
Trial website
Trial related presentations / publications
Public notes
The first HREC approval was obtained on the 24th of February 2012 in WA from the Royal Perth Hospital Ethics Level Five Kirkman House,Royal Perth Hospital, Murray Street. Approval was obtained on the 5th March 2019 and the first participant was subsequently recruited in WA. Collaborating Main AFFINITY Trial sites in the Eastern states later decided to join the sub study and the required HREC approval was subsequently sought. Recruitment in the sites under the Eastern States HREC did not commence until approval was obtained.

Contacts
Principal investigator
Name 89462 0
Prof Graeme Hankey
Address 89462 0
Harry Perkins Institute of Medical Research
2nd Floor, QQ Block
Sir Charles Gairdner Hospital
6 Verdun Street
Nedlands, Western Australia 6009
Country 89462 0
Australia
Phone 89462 0
+61 8 6151 1061
Fax 89462 0
Email 89462 0
graeme.hankey@uwa.edu.au
Contact person for public queries
Name 89463 0
Ms Anne Claxton
Address 89463 0
Harry Perkins Institute of Medical Research
2nd Floor, QQ Block
Sir Charles Gairdner Hospital
6 Verdun Street
Nedlands, Western Australia 6009
Country 89463 0
Australia
Phone 89463 0
+61 86151 1061
Fax 89463 0
Email 89463 0
anne.claxton@health.wa.gov.au
Contact person for scientific queries
Name 89464 0
Prof Graeme Hankey
Address 89464 0
Harry Perkins Institute of Medical Research
2nd Floor, QQ Block
Sir Charles Gairdner Hospital
6 Verdun Street
Nedlands, Western Australia 6009
Country 89464 0
Australia
Phone 89464 0
+61 86151 1061
Fax 89464 0
Email 89464 0
graeme.hankey@uwa.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