<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02205424</url>
  </required_header>
  <id_info>
    <org_study_id>APP-1020526</org_study_id>
    <nct_id>NCT02205424</nct_id>
  </id_info>
  <brief_title>Cognition And Neocortical Volume After Stroke</brief_title>
  <acronym>CANVAS</acronym>
  <official_title>Is Stroke Neurodegenerative? A Longitudinal Study of Brain Volume and Cognitive Decline Following Stroke (CANVAS: Cognition And Neocortical Volume After Stroke).</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The Florey Institute of Neuroscience and Mental Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Health and Medical Research Council, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The Florey Institute of Neuroscience and Mental Health</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Stroke and dementia are two of the most common and disabling conditions worldwide,&#xD;
      responsible for an enormous and growing burden of disease. There is increasing awareness that&#xD;
      the two conditions are linked, with cognitive impairment and dementia common after stroke,&#xD;
      vascular dementia accounting for about one-fifth of all dementia cases and recent evidence on&#xD;
      the contribution of vascular risk factors to Alzheimer's disease. Yet little is known about&#xD;
      whether brain volume loss - a hallmark of dementia - occurs after stroke, and whether such&#xD;
      atrophy is related to cognitive decline. The aim of this research is to establish whether&#xD;
      stroke patients have reductions in brain volume in the first three years post-stroke compared&#xD;
      to control subjects, and whether regional and global brain volume change is associated with&#xD;
      post-stroke dementia in order to elucidate potential causal mechanisms (including genetic&#xD;
      markers, amyloid deposition and vascular risk factors). The hypotheses are that stroke&#xD;
      patients will exhibit greater brain volume loss than comparable cohorts of stroke-free&#xD;
      controls, and further, that stroke patients who develop dementia will exhibit greater global&#xD;
      and regional brain volume loss than those who do not dement. An understanding of whether&#xD;
      stroke is neurodegenerative, and in which patients, may be used to help guide the early&#xD;
      delivery of disease-modifying therapies.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Our primary outcome measure was total brain volume (TBV) change between the 3-month and&#xD;
      3-year time-points compared between stroke patients and controls.&#xD;
&#xD;
      Secondary outcome 1 was TBV change between 3-months and 3-years comparing CN and CI stroke&#xD;
      participants. TBV at 3-months will be adjusted for CCI scores, and years of education; the&#xD;
      latter as it is correlated with cognitive performance and post-stroke dementia risk, but not&#xD;
      for stroke lesion volume as no conclusive evidence for an effect has been demonstrated&#xD;
      previously.&#xD;
&#xD;
      Secondary outcome 2 was hippocampal volume (HV) change between 3-months and 3-years in stroke&#xD;
      patients and controls with adjustments identical to primary outcome.&#xD;
&#xD;
      Secondary outcome 3 was the comparison of HV change between 3-months and 3-years comparing CN&#xD;
      and CI stroke participants with adjustments identical to secondary outcome 1.&#xD;
&#xD;
      See published protocol and uploaded statistical analysis plan for detailed description.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 1, 2011</start_date>
  <completion_date type="Actual">June 30, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Difference in total brain volume between 3 month and 3 year time-points</measure>
    <time_frame>Between 3 months and 3 years post-stroke</time_frame>
    <description>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</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>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.</measure>
    <time_frame>Between 3 months and 3 years post-stroke</time_frame>
    <description>Secondary outcome 1 was TBV change between 3-months and 3-years comparing CN and CI stroke participants.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Difference in hippocampal volume between 3 month and 3 year time-points in stroke and control participants.</measure>
    <time_frame>Between 3 months and 3 years post-stroke</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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.</measure>
    <time_frame>Between 3 months and 3 years post-stroke</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Actual">175</enrollment>
  <condition>Ischaemic Stroke</condition>
  <condition>Alzheimer's Disease</condition>
  <condition>Vascular Dementia</condition>
  <arm_group>
    <arm_group_label>Ischaemic stroke patients</arm_group_label>
    <description>Patients who have suffered an ischaemic stroke, as determined clinically and verified with imaging (CT brain; MRI).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy control participants</arm_group_label>
    <description>People who have never suffered a stroke, and are matched to the ischaemic stroke patient group according to age, education, and vascular risk factors.</description>
  </arm_group>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      Venous blood for APOE estimation.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Ischaemic stroke patients will have been admitted to the Acute Neurology Units of the&#xD;
        Austin Hospital (Heidelberg), Royal Melbourne Hospital (Parkville), and Box Hill Hospital&#xD;
        (Box Hill).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Clinical stroke&#xD;
&#xD;
          2. Aged greater than 18 years;&#xD;
&#xD;
          3. Able to have cognitive testing and MRI scan; and&#xD;
&#xD;
          4. Able to give informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Significant medical comorbidities precluding participation in cognitive testing, or&#xD;
             making survival for three years unlikely;&#xD;
&#xD;
          2. Normal exclusion criteria for MRI; e.g., implanted metal, severe claustrophobia;&#xD;
&#xD;
          3. Pre-existing dementia&#xD;
&#xD;
          4. Pregnancy, as a precaution to prevent exposing them to multiple MRI scans in a&#xD;
             12-month period&#xD;
&#xD;
          5. People in existing dependent or unequal relationships with any member of the research&#xD;
             team, to protect against coercion&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Amy G Brodtmann, MBBS PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Florey Institute of Neuroscience and Mental Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Eastern Health</name>
      <address>
        <city>Box Hill</city>
        <state>Victoria</state>
        <zip>3128</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Austin Health</name>
      <address>
        <city>Heidelberg</city>
        <state>Victoria</state>
        <zip>3084</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Melbourne Health</name>
      <address>
        <city>Parkville</city>
        <state>Victoria</state>
        <zip>3050</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <link>
    <url>https://www.medrxiv.org/content/10.1101/2021.08.03.21261461v1</url>
    <description>Primary and secondary hypotheses reporting</description>
  </link>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>March 20, 2014</study_first_submitted>
  <study_first_submitted_qc>July 30, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 31, 2014</study_first_posted>
  <last_update_submitted>June 9, 2022</last_update_submitted>
  <last_update_submitted_qc>June 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">June 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>The Florey Institute of Neuroscience and Mental Health</investigator_affiliation>
    <investigator_full_name>Amy Brodtmann</investigator_full_name>
    <investigator_title>Prof Amy Brodtmann</investigator_title>
  </responsible_party>
  <keyword>Ischaemic stroke</keyword>
  <keyword>Alzheimer's disease</keyword>
  <keyword>Brain volume</keyword>
  <keyword>Cortical thickness</keyword>
  <keyword>Magnetic Resonance Imaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Alzheimer Disease</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Dementia, Vascular</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02205424
org study id: APP-1020526
nct id: NCT02205424
lead sponsor: 
collaborator: 
has dmc: Yes
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.
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.
observational model: Cohort
time perspective: Prospective
measure: Difference in total brain volume between 3 month and 3 year time-points
time frame: Between 3 months and 3 years post-stroke
description: 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
measure: 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
description: Secondary outcome 1 was TBV change between 3-months and 3-years comparing CN and CI stroke participants.
measure: 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
description: 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.
measure: 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
description: 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.
arm group label: Ischaemic stroke patients
description: Patients who have suffered an ischaemic stroke, as determined clinically and verified with imaging (CT brain; MRI).
arm group label: Healthy control participants
description: People who have never suffered a stroke, and are matched to the ischaemic stroke patient group according to age, education, and vascular risk factors.
Venous blood for APOE estimation.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Amy G Brodtmann, MBBS PhD
role: Principal Investigator
affiliation: The Florey Institute of Neuroscience and Mental Health
facility: 
facility: 
facility: 
country: Australia
url: https://www.medrxiv.org/content/10.1101/2021.08.03.21261461v1
description: Primary and secondary hypotheses reporting
responsible party type: Principal Investigator
investigator affiliation: The Florey Institute of Neuroscience and Mental Health
investigator full name: Amy Brodtmann
investigator title: Prof Amy Brodtmann
mesh term: Stroke
mesh term: Alzheimer Disease
mesh term: Ischemic Stroke
mesh term: Dementia, Vascular
sharing ipd: No