<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/NCT03275155</url>
  </required_header>
  <id_info>
    <org_study_id>R-17-032</org_study_id>
    <nct_id>NCT03275155</nct_id>
  </id_info>
  <brief_title>Pathophysiology and Risk of Atrial Fibrillation Detected After Ischemic Stroke</brief_title>
  <acronym>PARADISE</acronym>
  <official_title>The PAthophysiology and Risk of Atrial Fibrillation Detected After Ischemic StrokE (PARADISE): Prospective Non-interventional Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Lawson Health Research Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Western University, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Western Ontario, Canada</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>London Health Sciences Centre</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Parkwood Hospital, London, Ontario</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>El Instituto de Neurociencia Cognitiva y Traslacional (INCYT)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Instituto de Neurologia Cognitiva (INECO)</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Lawson Health Research Institute</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This prospective non-interventional cohort study investigates the pathophysiology of Atrial&#xD;
      Fibrillation Detected After Stroke or transient ischemic attack (AFDAS) by comparing the&#xD;
      autonomic function and inflammation between patients with AFDAS, patients with atrial&#xD;
      fibrillation (AF) diagnosed before the ischemic event or known AF (KAF), and patients with&#xD;
      normal sinus rhythm (NSR) after 14 day of cardiac monitoring following the event onset.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study enrolls patients with acute ischemic stroke at the London Health Sciences Center&#xD;
      in London, Ontario, Canada. The heart rhythm of the patients is monitored with a CardioSTAT®&#xD;
      Holter device (Icentia) for 14 days after the ischemic event onset. Based on this cardiac&#xD;
      monitoring and previous medical history, patients are stratified into three groups: (a)&#xD;
      atrial fibrillation detected after stroke or transient ischemic attack (AFDAS), (b) atrial&#xD;
      fibrillation diagnosed before the ischemic event or known AF (KAF), and (c) normal sinus&#xD;
      rhythm (NSR).&#xD;
&#xD;
      Autonomic function is assessed by the levels of plasma catecholamines, a battery of validated&#xD;
      autonomic tests [autonomic reflex screening (ARS)], heart rate variability (HRV) through data&#xD;
      obtained by Holter monitoring by standard quantitative analysis methods according to the&#xD;
      guidelines of the European Society of Cardiology and the North American Society of Pacing and&#xD;
      Electrophysiology and by the analysis of diurnal variation of heart rate. Blood samples are&#xD;
      collected for the analysis of inflammatory markers (e.g. CRP, TNF-α, IL-1β, and IL-6), and&#xD;
      potential AFDAS predictors such as brain natriuretic peptide (BNP- AFDAS biomarker),&#xD;
      endothelin-1 (endothelial dysfunction marker), Lipoprotein(a) [Lp(a)] and&#xD;
      thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels, TAFI activity, TAFI single&#xD;
      nucleotide polymorphisms (SNPs), apo(a) isoform size and plasma catecholamines levels.&#xD;
      Furthermore, specific neuroimaging findings (e.g., specific regions of the insula or its&#xD;
      connections) and clinical features (e.g., impaired interoceptive processing, cognitive&#xD;
      impairment, etc) are also analyzed. Interoception is assessed using a heartbeat detection&#xD;
      task without feedback condition and gait, balance, frailty, and cognitive status in patients&#xD;
      are evaluated by the administration of a battery of tests. Stroke recurrence will be assessed&#xD;
      by a structured phone interview at 6 and 12 months after the initial stroke.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">April 18, 2017</start_date>
  <completion_date type="Anticipated">May 7, 2023</completion_date>
  <primary_completion_date type="Anticipated">May 7, 2023</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>Changes and Differences in Autonomic Function</measure>
    <time_frame>Within 48 hours of stroke onset and at 12, 30 and 90 days.</time_frame>
    <description>Differences in Composite Autonomic Severity Score (CASS) on an 11-point scale between patients with (a) AFDAS, (b) KAF , and (c) NSR</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes and Differences in Inflammatory Responses</measure>
    <time_frame>Within 48 hours of stroke onset and at 12, 30 and 90 days.</time_frame>
    <description>Differences in levels of plasma markers or temporal responses (CRP,TNFα, IL-6, IL-1β, etc) between patients with (a) AFDAS, (b)KAF and (c) NSR.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes and Differences in Heart Rate Variability (HRV)</measure>
    <time_frame>At 14 days.</time_frame>
    <description>Differences in HRV parameters between patients with (a) AFDAS, and (b) NSR</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Biomarkers</measure>
    <time_frame>Within 48 hours of stroke onset, at 12, 30 and 90 days and at 6 months.</time_frame>
    <description>Differences in levels of plasma markers (BNP,endothelin-1, Lp(a), and TAFI) or neuroimaging/clinical predictors between patients with (a) AFDAS , (b) KAF and (c) NSR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Atrial Fibrillation Burden</measure>
    <time_frame>At 14 days</time_frame>
    <description>Difference in atrial fibrillation burden (sum of atrial fibrillation episodes for a period of time) of AFDAS subjects with mild stroke/TIA compared to AFDAS subjects with moderate/severe stroke.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gait Impairments</measure>
    <time_frame>At 6 months</time_frame>
    <description>Differences in gait parameters in patients with a) AFDAS , (b) KAF and (c) NSR.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Frailty</measure>
    <time_frame>At 6 months</time_frame>
    <description>Differences in frailty in patients with (a) AFDAS , (b) KAF and (c) NSR</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive Impairment</measure>
    <time_frame>At 6 months</time_frame>
    <description>Differences in cognition in patients with (a) AFDAS , (b) KAF and (c) NSR</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Stroke Recurrence</measure>
    <time_frame>At 90, 180, and 360 days</time_frame>
    <description>Number of stroke recurrences in patients with (a) AFDAS , (b) KAF and (c) NSR</description>
  </other_outcome>
  <other_outcome>
    <measure>Death</measure>
    <time_frame>At 90, 180, and 360 days</time_frame>
    <description>Number of deaths in (a) AFDAS , (b) KAF and (c) NSR groups</description>
  </other_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Anticipated">100</enrollment>
  <condition>Stroke, Ischemic</condition>
  <condition>Transient Ischemic Attack</condition>
  <condition>Atrial Fibrillation</condition>
  <arm_group>
    <arm_group_label>AFDAS</arm_group_label>
    <description>patients without history of atrial fibrillation before the qualifying stroke or transient ischemic attack who are diagnosed with atrial fibrillation during the 14 days of monitoring</description>
  </arm_group>
  <arm_group>
    <arm_group_label>KAF</arm_group_label>
    <description>atrial fibrillation known before the stroke or transient ischemic attack</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NSR</arm_group_label>
    <description>patients without a history of atrial fibrillation who do not develop atrial fibrillation during the 14 days of cardiac monitoring</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Ischemic stroke and transient ischemic attack patients presenting at the University&#xD;
        Hospital of the London Health Science Center, London, Ontario, Canada.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. MCA territory-transient ischemic attack or -acute ischemic stroke patients seen in the&#xD;
             Emergency Department or admitted to University Hospital, London, Ontario, Canada&#xD;
&#xD;
          2. Age ≥ 18 years old&#xD;
&#xD;
          3. Patient or Substitute Decision Maker must give written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients with autonomic dysfunction such as Parkinson's disease that can be&#xD;
             interfering with outcome assessment based on qualified investigator's judgment.&#xD;
&#xD;
          2. Patients taking tricyclic antidepressant (TCAs)&#xD;
&#xD;
          3. Patients in whom the acute stroke is primarily hemorrhagic&#xD;
&#xD;
          4. Patients with both TIA and atrial fibrillation&#xD;
&#xD;
          5. Patients with both TIA and large vessel disease&#xD;
&#xD;
          6. Patients with inflammatory diseases&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Luciano A Sposato, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Lawson Health Research Institute, London Health Sciences Center, Western University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University Hospital, London Helath Sciences Center</name>
      <address>
        <city>London</city>
        <state>Ontario</state>
        <zip>N6A 5A5</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>August 24, 2017</study_first_submitted>
  <study_first_submitted_qc>September 5, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 7, 2017</study_first_posted>
  <last_update_submitted>May 10, 2022</last_update_submitted>
  <last_update_submitted_qc>May 10, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 11, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Autonomic Dysfunction</keyword>
  <keyword>Inflammation</keyword>
  <keyword>Cognitive impairment</keyword>
  <keyword>Interoception</keyword>
  <keyword>Gait impairment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Ischemic Attack, Transient</mesh_term>
    <mesh_term>Atrial Fibrillation</mesh_term>
    <mesh_term>Ischemia</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/NCT03275155
org study id: R-17-032
nct id: NCT03275155
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This prospective non-interventional cohort study investigates the pathophysiology of Atrial
      Fibrillation Detected After Stroke or transient ischemic attack (AFDAS) by comparing the
      autonomic function and inflammation between patients with AFDAS, patients with atrial
      fibrillation (AF) diagnosed before the ischemic event or known AF (KAF), and patients with
      normal sinus rhythm (NSR) after 14 day of cardiac monitoring following the event onset.
This study enrolls patients with acute ischemic stroke at the London Health Sciences Center
      in London, Ontario, Canada. The heart rhythm of the patients is monitored with a CardioSTAT®
      Holter device (Icentia) for 14 days after the ischemic event onset. Based on this cardiac
      monitoring and previous medical history, patients are stratified into three groups: (a)
      atrial fibrillation detected after stroke or transient ischemic attack (AFDAS), (b) atrial
      fibrillation diagnosed before the ischemic event or known AF (KAF), and (c) normal sinus
      rhythm (NSR).

      Autonomic function is assessed by the levels of plasma catecholamines, a battery of validated
      autonomic tests [autonomic reflex screening (ARS)], heart rate variability (HRV) through data
      obtained by Holter monitoring by standard quantitative analysis methods according to the
      guidelines of the European Society of Cardiology and the North American Society of Pacing and
      Electrophysiology and by the analysis of diurnal variation of heart rate. Blood samples are
      collected for the analysis of inflammatory markers (e.g. CRP, TNF-α, IL-1β, and IL-6), and
      potential AFDAS predictors such as brain natriuretic peptide (BNP- AFDAS biomarker),
      endothelin-1 (endothelial dysfunction marker), Lipoprotein(a) [Lp(a)] and
      thrombin-activatable fibrinolysis inhibitor (TAFI) plasma levels, TAFI activity, TAFI single
      nucleotide polymorphisms (SNPs), apo(a) isoform size and plasma catecholamines levels.
      Furthermore, specific neuroimaging findings (e.g., specific regions of the insula or its
      connections) and clinical features (e.g., impaired interoceptive processing, cognitive
      impairment, etc) are also analyzed. Interoception is assessed using a heartbeat detection
      task without feedback condition and gait, balance, frailty, and cognitive status in patients
      are evaluated by the administration of a battery of tests. Stroke recurrence will be assessed
      by a structured phone interview at 6 and 12 months after the initial stroke.
observational model: Cohort
time perspective: Prospective
measure: Changes and Differences in Autonomic Function
time frame: Within 48 hours of stroke onset and at 12, 30 and 90 days.
description: Differences in Composite Autonomic Severity Score (CASS) on an 11-point scale between patients with (a) AFDAS, (b) KAF , and (c) NSR
measure: Changes and Differences in Inflammatory Responses
time frame: Within 48 hours of stroke onset and at 12, 30 and 90 days.
description: Differences in levels of plasma markers or temporal responses (CRP,TNFα, IL-6, IL-1β, etc) between patients with (a) AFDAS, (b)KAF and (c) NSR.
measure: Changes and Differences in Heart Rate Variability (HRV)
time frame: At 14 days.
description: Differences in HRV parameters between patients with (a) AFDAS, and (b) NSR
measure: Biomarkers
time frame: Within 48 hours of stroke onset, at 12, 30 and 90 days and at 6 months.
description: Differences in levels of plasma markers (BNP,endothelin-1, Lp(a), and TAFI) or neuroimaging/clinical predictors between patients with (a) AFDAS , (b) KAF and (c) NSR
measure: Atrial Fibrillation Burden
time frame: At 14 days
description: Difference in atrial fibrillation burden (sum of atrial fibrillation episodes for a period of time) of AFDAS subjects with mild stroke/TIA compared to AFDAS subjects with moderate/severe stroke.
measure: Gait Impairments
time frame: At 6 months
description: Differences in gait parameters in patients with a) AFDAS , (b) KAF and (c) NSR.
measure: Frailty
time frame: At 6 months
description: Differences in frailty in patients with (a) AFDAS , (b) KAF and (c) NSR
measure: Cognitive Impairment
time frame: At 6 months
description: Differences in cognition in patients with (a) AFDAS , (b) KAF and (c) NSR
measure: Stroke Recurrence
time frame: At 90, 180, and 360 days
description: Number of stroke recurrences in patients with (a) AFDAS , (b) KAF and (c) NSR
measure: Death
time frame: At 90, 180, and 360 days
description: Number of deaths in (a) AFDAS , (b) KAF and (c) NSR groups
arm group label: AFDAS
description: patients without history of atrial fibrillation before the qualifying stroke or transient ischemic attack who are diagnosed with atrial fibrillation during the 14 days of monitoring
arm group label: KAF
description: atrial fibrillation known before the stroke or transient ischemic attack
arm group label: NSR
description: patients without a history of atrial fibrillation who do not develop atrial fibrillation during the 14 days of cardiac monitoring
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Luciano A Sposato, MD
role: Principal Investigator
affiliation: Lawson Health Research Institute, London Health Sciences Center, Western University
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Ischemic Attack, Transient
mesh term: Atrial Fibrillation
mesh term: Ischemia
sharing ipd: No