Ischaemic StrokeCANVASNCT02205424
Cognition And Neocortical Volume After Stroke
An observational study of Ischaemic Stroke and Alzheimer's Disease, run by The Florey Institute of Neuroscience and Mental Health at 3 sites in Australia.
Trial summary
Stroke and dementia are two of the most common and disabling conditions worldwide, responsible for an enormous and growing burden of disease. There is increasing awareness that the two conditions are linked, with cognitive impairment and dementia common after stroke, vascular dementia accounting for about one-fifth of… Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Ischaemic Stroke, Alzheimer's Disease, Vascular Dementia
- How many people
- 175 participants
- Where
- 3 sitesAustralia
- Study dates
- 1 May 2011to 30 Jun 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Ischaemic stroke patients will have been admitted to the Acute Neurology Units of the Austin Hospital (Heidelberg), Royal Melbourne Hospital (Parkville), and Box Hill Hospital (Box Hill).
Who may be able to join
- Clinical stroke
- Aged greater than 18 years;
- Able to have cognitive testing and MRI scan; and
- Able to give informed consent
Who cannot join
- Significant medical comorbidities precluding participation in cognitive testing, or making survival for three years unlikely;
- Normal exclusion criteria for MRI; e.g., implanted metal, severe claustrophobia;
- Pre-existing dementia
- Pregnancy, as a precaution to prevent exposing them to multiple MRI scans in a 12-month period
- People in existing dependent or unequal relationships with any member of the research team, to protect against coercion
Trial locations and contacts
3 sites in 1 country.
Australia3 sites
Eastern Health
Box Hill, Victoria, 3128
Austin Health
Heidelberg, Victoria, 3084
Melbourne Health
Parkville, Victoria, 3050
About this study
Official title: Is Stroke Neurodegenerative? A Longitudinal Study of Brain Volume and Cognitive Decline Following Stroke (CANVAS: Cognition And Neocortical Volume After Stroke).
Stroke and dementia are two of the most common and disabling conditions worldwide, responsible for an enormous and growing burden of disease. There is increasing awareness that the two conditions are linked, with cognitive impairment and dementia common after stroke, vascular dementia accounting for about one-fifth of all dementia cases and recent evidence on the contribution of vascular risk factors to Alzheimer's disease. Yet little is known about whether brain volume loss - a hallmark of dementia - occurs after stroke, and whether such atrophy is related to cognitive decline. The aim of this research is to establish whether stroke patients have reductions in brain volume in the first three years post-stroke compared to control subjects, and whether regional and global brain volume change is associated with post-stroke dementia in order to elucidate potential causal mechanisms (including genetic markers, amyloid deposition and vascular risk factors). The hypotheses are that stroke patients will exhibit greater brain volume loss than comparable cohorts of stroke-free controls, and further, that stroke patients who develop dementia will exhibit greater global and regional brain volume loss than those who do not dement. An understanding of whether stroke is neurodegenerative, and in which patients, may be used to help guide the early delivery of disease-modifying therapies.
Read the detailed description
Our primary outcome measure was total brain volume (TBV) change between the 3-month and 3-year time-points compared between stroke patients and controls.
Secondary outcome 1 was TBV change between 3-months and 3-years comparing CN and CI stroke participants. TBV at 3-months will be adjusted for CCI scores, and years of education; the latter as it is correlated with cognitive performance and post-stroke dementia risk, but not for stroke lesion volume as no conclusive evidence for an effect has been demonstrated previously.
Secondary outcome 2 was hippocampal volume (HV) change between 3-months and 3-years in stroke patients and controls with adjustments identical to primary outcome.
Secondary outcome 3 was the comparison of HV change between 3-months and 3-years comparing CN and CI stroke participants with adjustments identical to secondary outcome 1.
See published protocol and uploaded statistical analysis plan for detailed description.
- Conditions
- Ischaemic Stroke, Alzheimer's Disease, Vascular Dementia
- Keywords
- Ischaemic stroke, Alzheimer's disease, Brain volume, Cortical thickness, Magnetic Resonance Imaging
- Medical subject headings
- Ischemic Stroke, Alzheimer Disease, Dementia, Vascular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Ischaemic stroke patients | Patients who have suffered an ischaemic stroke, as determined clinically and verified with imaging (CT brain; MRI). | |
| Healthy control participants | People who have never suffered a stroke, and are matched to the ischaemic stroke patient group according to age, education, and vascular risk factors. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Difference in total brain volume between 3 month and 3 year time-points
We will examine changes in brain volume between the 3 month and 3 year time-points in ischemic stroke patients and healthy age-matched control participants
Measured: Between 3 months and 3 years post-stroke
Secondary outcomes (3)
Comparison of total brain volume (TBV) change between 3 month and 3 year time-points in those who were cognitively normal (CN) versus cognitively impaired (CI) determined at the 3 months post-stroke time point.
Secondary outcome 1 was TBV change between 3-months and 3-years comparing CN and CI stroke participants.
Measured: Between 3 months and 3 years post-stroke
Difference in hippocampal volume between 3 month and 3 year time-points in stroke and control participants.
Secondary outcome 2 was hippocampal volume (HV) change between 3-months and 3-years in stroke patients and controls with adjustments identical to primary outcome.
Measured: Between 3 months and 3 years post-stroke
Comparison of hippocampal volume change between 3 month and 3 year time-points in those who were cognitively normal versus cognitively impaired at 3 months post-stroke.
Secondary outcome 3 was the comparison of HV change between 3-months and 3-years comparing CN and CI stroke participants with adjustments identical to secondary outcome 1.
Measured: Between 3 months and 3 years post-stroke
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2014 (estimated)
- Study start1 May 2011
- Primary completion31 Dec 2020
- Study completion30 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Ischaemic StrokeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 175 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Florey Institute of Neuroscience and Mental Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Health and Medical Research Council, Australia
- Responsible party
- Principal investigator, Amy Brodtmann, The Florey Institute of Neuroscience and Mental Health
- Investigators
- Amy G Brodtmann, MBBS PhD, Principal investigator, The Florey Institute of Neuroscience and Mental Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02205424
- Sponsor's protocol ID
- APP-1020526
- Acronym
- CANVAS
- Status last verified
- Jun 2022
- First submitted
- 20 Mar 2014
- Last updated
- 10 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Egorova-Brumley N, Dhollander T, Khan W, Khlif MS, Ebaid D, Brodtmann A. Changes in White Matter Microstructure Over 3 Years in People With and Without Stroke. Neurology. 2023 Apr 18;100(16):e1664-e1672. doi: 10.1212/WNL.0000000000207065. Epub 2023 Feb 15.
PubMed 36792378Hung SH, Khlif MS, Kramer S, Werden E, Bird LJ, Campbell BCV, Brodtmann A. Poststroke White Matter Hyperintensities and Physical Activity: A CANVAS Study Exploratory Analysis. Med Sci Sports Exerc. 2022 Sep 1;54(9):1401-1409. doi: 10.1249/MSS.0000000000002946. Epub 2022 Apr 25.
PubMed 35482768Brodtmann A, Werden E, Khlif MS, Bird LJ, Egorova N, Veldsman M, Pardoe H, Jackson G, Bradshaw J, Darby D, Cumming T, Churilov L, Donnan G. Neurodegeneration Over 3 Years Following Ischaemic Stroke: Findings From the Cognition and Neocortical Volume After Stroke Study. Front Neurol. 2021 Oct 22;12:754204. doi: 10.3389/fneur.2021.754204. eCollection 2021.
PubMed 34744989Brodtmann A, Khlif MS, Egorova N, Veldsman M, Bird LJ, Werden E. Dynamic Regional Brain Atrophy Rates in the First Year After Ischemic Stroke. Stroke. 2020 Sep;51(9):e183-e192. doi: 10.1161/STROKEAHA.120.030256. Epub 2020 Aug 10.
PubMed 32772680
Study at a glance
From the registry record, last updated by the sponsor on 10 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Is Stroke Neurodegenerative? A Longitudinal Study of Brain Volume and Cognitive Decline Following Stroke (CANVAS: Cognition And Neocortical Volume After Stroke).
- ClinicalTrials.gov ID
- NCT02205424
- Acronym / sponsor ID
- CANVAS / APP-1020526
- Conditions
- Ischaemic Stroke, Alzheimer's Disease, Vascular Dementia
- Keywords
- Ischaemic stroke, Alzheimer's disease, Brain volume, Cortical thickness, Magnetic Resonance Imaging
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 175 participants (actual)
- Lead sponsor
- The Florey Institute of Neuroscience and Mental HealthUniversity, hospital or other
- Collaborators
- National Health and Medical Research Council, Australia
- Study start
- 1 May 2011 (actual)
- Primary completion
- 31 Dec 2020 (actual)
- Study completion
- 30 Jun 2021 (actual)
- First posted
- 31 Jul 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Stroke and dementia are two of the most common and disabling conditions worldwide, responsible for an enormous and growing burden of disease. There is increasing awareness that the two conditions are linked, with cognitive impairment and dementia common after stroke, vascular dementia accounting for about one-fifth of all dementia cases and recent evidence on the contribution of vascular risk factors to Alzheimer's disease. Yet little is known about whether brain volume loss - a hallmark of dementia - occurs after stroke, and whether such atrophy is related to cognitive decline. The aim of this research is to establish whether stroke patients have reductions in brain volume in the first three years post-stroke compared to control subjects, and whether regional and global brain volume change is associated with post-stroke dementia in order to elucidate potential causal mechanisms (including genetic markers, amyloid deposition and vascular risk factors). The hypotheses are that stroke patients will exhibit greater brain volume loss than comparable cohorts of stroke-free controls, and further, that stroke patients who develop dementia will exhibit greater global and regional brain volume loss than those who do not dement. An understanding of whether stroke is neurodegenerative, and in which patients, may be used to help guide the early delivery of disease-modifying therapies.
Detailed description
Our primary outcome measure was total brain volume (TBV) change between the 3-month and 3-year time-points compared between stroke patients and controls.
Secondary outcome 1 was TBV change between 3-months and 3-years comparing CN and CI stroke participants. TBV at 3-months will be adjusted for CCI scores, and years of education; the latter as it is correlated with cognitive performance and post-stroke dementia risk, but not for stroke lesion volume as no conclusive evidence for an effect has been demonstrated previously.
Secondary outcome 2 was hippocampal volume (HV) change between 3-months and 3-years in stroke patients and controls with adjustments identical to primary outcome.
Secondary outcome 3 was the comparison of HV change between 3-months and 3-years comparing CN and CI stroke participants with adjustments identical to secondary outcome 1.
See published protocol and uploaded statistical analysis plan for detailed description.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ischaemic stroke patients | – | –Patients who have suffered an ischaemic stroke, as determined clinically and verified with imaging (CT brain; MRI). |
| Healthy control participants | – | –People who have never suffered a stroke, and are matched to the ischaemic stroke patient group according to age, education, and vascular risk factors. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Ischaemic stroke patients will have been admitted to the Acute Neurology Units of the Austin Hospital (Heidelberg), Royal Melbourne Hospital (Parkville), and Box Hill Hospital (Box Hill).
Key inclusion criteria (4 listed)
- Clinical stroke
- Aged greater than 18 years;
- Able to have cognitive testing and MRI scan; and
- Able to give informed consent
Key exclusion criteria (5 listed)
- Significant medical comorbidities precluding participation in cognitive testing, or making survival for three years unlikely;
- Normal exclusion criteria for MRI; e.g., implanted metal, severe claustrophobia;
- Pre-existing dementia
- Pregnancy, as a precaution to prevent exposing them to multiple MRI scans in a 12-month period
- People in existing dependent or unequal relationships with any member of the research team, to protect against coercion
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Difference in total brain volume between 3 month and 3 year time-points
Time frame: Between 3 months and 3 years post-stroke
We will examine changes in brain volume between the 3 month and 3 year time-points in ischemic stroke patients and healthy age-matched control participants
3 secondary outcomes
Comparison of total brain volume (TBV) change between 3 month and 3 year time-points in those who were cognitively normal (CN) versus cognitively impaired (CI) determined at the 3 months post-stroke time point.
Time frame: Between 3 months and 3 years post-stroke
Difference in hippocampal volume between 3 month and 3 year time-points in stroke and control participants.
Time frame: Between 3 months and 3 years post-stroke
Comparison of hippocampal volume change between 3 month and 3 year time-points in those who were cognitively normal versus cognitively impaired at 3 months post-stroke.
Time frame: Between 3 months and 3 years post-stroke
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jun 2022.
- Derived from this study: PubMed 36792378Egorova-Brumley N, Dhollander T, Khan W, Khlif MS, Ebaid D, Brodtmann A. Changes in White Matter Microstructure Over 3 Years in People With and Without Stroke. Neurology. 2023 Apr 18;100(16):e1664-e1672. doi: 10.1212/WNL.0000000000207065. Epub 2023 Feb 15.
- Derived from this study: PubMed 35482768Hung SH, Khlif MS, Kramer S, Werden E, Bird LJ, Campbell BCV, Brodtmann A. Poststroke White Matter Hyperintensities and Physical Activity: A CANVAS Study Exploratory Analysis. Med Sci Sports Exerc. 2022 Sep 1;54(9):1401-1409. doi: 10.1249/MSS.0000000000002946. Epub 2022 Apr 25.
- Derived from this study: PubMed 34744989Brodtmann A, Werden E, Khlif MS, Bird LJ, Egorova N, Veldsman M, Pardoe H, Jackson G, Bradshaw J, Darby D, Cumming T, Churilov L, Donnan G. Neurodegeneration Over 3 Years Following Ischaemic Stroke: Findings From the Cognition and Neocortical Volume After Stroke Study. Front Neurol. 2021 Oct 22;12:754204. doi: 10.3389/fneur.2021.754204. eCollection 2021.
- Derived from this study: PubMed 32772680Brodtmann A, Khlif MS, Egorova N, Veldsman M, Bird LJ, Werden E. Dynamic Regional Brain Atrophy Rates in the First Year After Ischemic Stroke. Stroke. 2020 Sep;51(9):e183-e192. doi: 10.1161/STROKEAHA.120.030256. Epub 2020 Aug 10.
- The Florey Institute of Neuroscience and Mental Health: The CANVAS projectLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Ischaemic Stroke
Recruiting
Connectomic Alterations Following Acute Ischemic Stroke in the MCA Territory
Ischemic Stroke
Active, not recruitingPhase 4
A Study Testing How Well the Drug Extract of Ginkgo Biloba Leaves Tablets Works for People With Memory or Thinking Problems After a Stroke When Added to Standard Treatment
Ischemic Stroke Hospitalized, Impairment, Cognitive
Not yet recruitingPhase 4
Anti-inflammatory and Anti-thrombotic Therapy With colcHicine and Low Dose Rivaroxaban for Major Adverse Cardiovascular Events Reduction in Ischemic Stroke
Ischemic Stroke
RecruitingPhase 3
Probucol for Symptomatic Intracranial and Extracranial Artery Stenosis
Ischemic Stroke, TIA
Recruiting
MindEx: A Novel, Multifocal, Cognitive Brain-Machine Interface System
Paralysis; Quadriplegic, Quadraplegia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amy G Brodtmann, MBBS PhD principal investigator
The Florey Institute of Neuroscience and Mental Health
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ischaemic Stroke and Alzheimer's Disease, run by The Florey Institute of Neuroscience and Mental Health at 3 sites in Australia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Australia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Difference in total brain volume between 3 month and 3 year time-points (time frame: Between 3 months and 3 years post-stroke). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02205424, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jun 2022.