<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/NCT04412187</url>
  </required_header>
  <id_info>
    <org_study_id>19-428</org_study_id>
    <nct_id>NCT04412187</nct_id>
  </id_info>
  <brief_title>Inflammatory faCtors AfteR acUte Ischemic Stroke</brief_title>
  <acronym>ICARUS</acronym>
  <official_title>Inflammatory faCtors AfteR acUte Ischemic Stroke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Martin Dichgans</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Universitätsklinikum Hamburg-Eppendorf</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University Hospital Muenster</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Ludwig-Maximilians - University of Munich</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>
      ICARUS is an interventional single-centre hospital-based cohort study in patients admitted to&#xD;
      the stroke unit with an acute ischemic stroke. The aims of the study are to i) define the&#xD;
      characteristics and determinants of microglial activation after human stroke, and ii) assess&#xD;
      the correlation of microglial activation with circulating inflammatory markers, structural&#xD;
      brain changes on neuroimaging, and neurological outcomes.&#xD;
&#xD;
      ICARUS involves serial TSPO-PET imaging along with serial MRI, immune cell profiling in&#xD;
      blood, and both clinical and laboratory assessments in 36 patients with acute ischemic stroke&#xD;
      caused by a cortical (N=18) or strictly subcortical (N=18) infarct.&#xD;
&#xD;
      In a substudy, the investigators will include 10 independently recruited patients with acute&#xD;
      ischemic stroke to assess MRI arterial spin labelling (ASL) sequences as a marker for&#xD;
      perfusion measurement of the TSPO tracer.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The neuroinflammatory response after ischemic brain injury has been identified as a&#xD;
      pathomechanism in ischemic stroke. Stroke induces an activation of microglia in the brain,&#xD;
      which lasts over months. However, the characteristics and mechanisms of this microglia&#xD;
      activation are insufficiently defined.&#xD;
&#xD;
      Our study hypotheses are (i) that a subpopulation of patients with acute stroke develop&#xD;
      prominent microglial activation, and (ii) that patients with extensive microglial activation&#xD;
      are more likely to experience poor outcome.&#xD;
&#xD;
      Against this background, the investigators set up the &quot;Inflammatory faCtors AfteR acUte&#xD;
      ischemic Stroke (ICARUS)&quot; study as an interventional single-centre hospital-based cohort&#xD;
      study. N=36 patients with a cortical (N=18) or strictly subcortical (N=18) acute ischemic&#xD;
      stroke will be recruited through the local stroke unit (Department of Neurology, LMU Munich).&#xD;
      Study participation involves serial TSPO-PET imaging along with serial MR imaging, immune&#xD;
      cell profiling in blood, and both clinical and laboratory assessments. Follow-up assessments&#xD;
      at 3 weeks, 3 months, 6 months and 12 months will be conducted at the Institute for Stroke&#xD;
      and Dementia Research (ISD) and at the Department of Nuclear medicine, both LMU Munich.&#xD;
&#xD;
      In a substudy, the investigators will include 10 independently recruited patients with acute&#xD;
      ischemic stroke to assess MRI arterial spin labelling (ASL) sequences as a marker for&#xD;
      perfusion measurement of the TSPO tracer. These patients will receive dynamic PET in addition&#xD;
      to the ASL sequences.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2020</start_date>
  <completion_date type="Anticipated">November 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">November 30, 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>18 patients with cortical stroke and 18 patients with subcortical stroke</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>microglia activation in patients with acute stroke</measure>
    <time_frame>within 10 days after acute ischemic stroke</time_frame>
    <description>Microglia activation will be assessed using TSPO PET imgaing.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>microglia activation in patients with acute stroke</measure>
    <time_frame>3 months after acute ischemic stroke</time_frame>
    <description>Microglia activation will be assessed using TSPO PET imgaing.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>functional outcome in patients after acute ischemic stroke</measure>
    <time_frame>3 weeks after acute ischemic stroke</time_frame>
    <description>Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>functional outcome in patients after acute ischemic stroke</measure>
    <time_frame>3 months after acute ischemic stroke</time_frame>
    <description>Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>functional outcome in patients after acute ischemic stroke</measure>
    <time_frame>6 months after acute ischemic stroke</time_frame>
    <description>Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>functional outcome in patients after acute ischemic stroke</measure>
    <time_frame>12 months after acute ischemic stroke</time_frame>
    <description>Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>cognitive outcome in patients after acute ischemic stroke</measure>
    <time_frame>3 weeks after acute ischemic stroke</time_frame>
    <description>Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>cognitive outcome in patients after acute ischemic stroke</measure>
    <time_frame>3 months after acute ischemic stroke</time_frame>
    <description>Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>cognitive outcome in patients after acute ischemic stroke</measure>
    <time_frame>6 months after acute ischemic stroke</time_frame>
    <description>Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>cognitive outcome in patients after acute ischemic stroke</measure>
    <time_frame>12 months after acute ischemic stroke</time_frame>
    <description>Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>inflammatory markers in blood</measure>
    <time_frame>3 weeks after acute ischemic stroke</time_frame>
    <description>Inflammatory markers in blood will be assessed by flow cytometry and related to microglial activation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>inflammatory markers in blood</measure>
    <time_frame>3 months after acute ischemic stroke</time_frame>
    <description>Inflammatory markers in blood will be assessed by flow cytometry and related to microglial activation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duplex ultrasound</measure>
    <time_frame>6 months after acute ischemic stroke</time_frame>
    <description>Duplex ultrasound will be performed to assess potential progress of atherosclerosis related to inflammatory markers</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3T MR imaging</measure>
    <time_frame>3 months after acute ischemic stroke</time_frame>
    <description>3T MRI will be performed to relate infarct evolution, secondary neurodegeneration, and stroke outcome to microglial activation.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>3T MR imaging</measure>
    <time_frame>12 months after acute ischemic stroke</time_frame>
    <description>3T MRI will be performed to relate infarct evolution, secondary neurodegeneration, and stroke outcome to microglial activation.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">36</enrollment>
  <condition>Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>TSPO PET imaging</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All study participants will receive [18F]-GE-180, i.e. TSPO PET imaging to assess microglia activation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>[18F]-GE-180 PET</intervention_name>
    <description>serial [18F]-GE-180 PET imaging to assess microglia activation</description>
    <arm_group_label>TSPO PET imaging</arm_group_label>
    <other_name>TSPO PET imaging</other_name>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>3T MRI</intervention_name>
    <description>serial MR imaging (i) to determine infarct characteristics, (ii) to identify gray and white matter structures connected to the infarct, (iii) to detect incident lesions, and (iv) to quantify longitudinal changes e.g. of cortical thickness</description>
    <arm_group_label>TSPO PET imaging</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Diagnostic Test</intervention_type>
    <intervention_name>immune cell profiling in blood</intervention_name>
    <description>Cell-specific cytokine profiles, markers of activation, terminal differentiation as well as cytotoxicity will be assesses using flow cytometry.</description>
    <arm_group_label>TSPO PET imaging</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 50 years&#xD;
&#xD;
          -  Acute ischemic stroke (time frame: &lt;72 hours) as defined by an acute focal&#xD;
             neurological deficit in combination with a corresponding infarct as documented by a&#xD;
             diffusion weighted imaging (DWI)-positive lesion on magnetic resonance imaging (MRI);&#xD;
             presence of an infarct involving the cortex or a strictly subcortical infarct&#xD;
&#xD;
          -  Written informed consent prior to study participation&#xD;
&#xD;
          -  Willingness to participate in study assessments including follow-up&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unwillingness or inability to give written consent&#xD;
&#xD;
          -  Prior history of stroke, multiple infarcts, infratentorial infarcts affecting the&#xD;
             brain stem or cerebellum&#xD;
&#xD;
          -  Known diseases of the CNS other than stroke&#xD;
&#xD;
          -  Immunomodulatory therapies within the last 3 months prior stroke&#xD;
&#xD;
          -  Chronic inflammatory disease&#xD;
&#xD;
          -  Infectious diseases within the last 7 days prior stroke&#xD;
&#xD;
          -  Conditions interfering with follow-up such as end-stage malignancy&#xD;
&#xD;
          -  Contraindications for MRI or PET (pacemaker, aneurysm clip, cochlear implant etc.)&#xD;
&#xD;
          -  Radiation exposure of &gt; 10mSv per year&#xD;
&#xD;
          -  Pregnant or breastfeeding women&#xD;
&#xD;
          -  Participation in a clinical trial&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Martin Dichgans, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>LMU Munich</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Peter Bartenstein, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>LMU Munich</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Sibylle Ziegler, Prof.</last_name>
    <role>Principal Investigator</role>
    <affiliation>LMU Munich</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Martin Dichgans, Prof.</last_name>
    <phone>+49 4400</phone>
    <phone_ext>46019</phone_ext>
    <email>martin.dichgans@med.uni-muenchen.de</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Anna Kopczak, MD</last_name>
    <phone>+49 4400</phone>
    <phone_ext>46125</phone_ext>
    <email>anna.kopczak@med.uni-muenchen.de</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Department of Nuclear Medicine</name>
      <address>
        <city>Munich</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Peter Bartenstein, Prof.</last_name>
      <phone>+49 89 4400</phone>
      <phone_ext>77646</phone_ext>
      <email>peter.bartenstein@med.uni-muenchen.de</email>
    </contact>
    <contact_backup>
      <last_name>Matthias Brendel, MD</last_name>
      <phone>+49 89 4400</phone>
      <phone_ext>74646</phone_ext>
      <email>matthias.brendel@med.uni-muenchen.de</email>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Insitute for Stroke and Dementia Research</name>
      <address>
        <city>Munich</city>
        <zip>81377</zip>
        <country>Germany</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Martin Dichgans, Prof.</last_name>
      <phone>+49 89 4400</phone>
      <phone_ext>46019</phone_ext>
    </contact>
    <contact_backup>
      <last_name>Anna Kopczak, MD</last_name>
      <phone>+49 89 4400</phone>
      <phone_ext>46125</phone_ext>
    </contact_backup>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>May 22, 2020</study_first_submitted>
  <study_first_submitted_qc>May 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 2, 2020</study_first_posted>
  <last_update_submitted>March 7, 2023</last_update_submitted>
  <last_update_submitted_qc>March 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 8, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Ludwig-Maximilians - University of Munich</investigator_affiliation>
    <investigator_full_name>Martin Dichgans</investigator_full_name>
    <investigator_title>Prof. Dr. Martin Dichgans</investigator_title>
  </responsible_party>
  <keyword>microglia</keyword>
  <keyword>neuroinflammation</keyword>
  <keyword>functional outcome after stroke</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>Cerebral Infarction</mesh_term>
    <mesh_term>Ischemia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT04412187
org study id: 19-428
nct id: NCT04412187
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
ICARUS is an interventional single-centre hospital-based cohort study in patients admitted to
      the stroke unit with an acute ischemic stroke. The aims of the study are to i) define the
      characteristics and determinants of microglial activation after human stroke, and ii) assess
      the correlation of microglial activation with circulating inflammatory markers, structural
      brain changes on neuroimaging, and neurological outcomes.

      ICARUS involves serial TSPO-PET imaging along with serial MRI, immune cell profiling in
      blood, and both clinical and laboratory assessments in 36 patients with acute ischemic stroke
      caused by a cortical (N=18) or strictly subcortical (N=18) infarct.

      In a substudy, the investigators will include 10 independently recruited patients with acute
      ischemic stroke to assess MRI arterial spin labelling (ASL) sequences as a marker for
      perfusion measurement of the TSPO tracer.
The neuroinflammatory response after ischemic brain injury has been identified as a
      pathomechanism in ischemic stroke. Stroke induces an activation of microglia in the brain,
      which lasts over months. However, the characteristics and mechanisms of this microglia
      activation are insufficiently defined.

      Our study hypotheses are (i) that a subpopulation of patients with acute stroke develop
      prominent microglial activation, and (ii) that patients with extensive microglial activation
      are more likely to experience poor outcome.

      Against this background, the investigators set up the "Inflammatory faCtors AfteR acUte
      ischemic Stroke (ICARUS)" study as an interventional single-centre hospital-based cohort
      study. N=36 patients with a cortical (N=18) or strictly subcortical (N=18) acute ischemic
      stroke will be recruited through the local stroke unit (Department of Neurology, LMU Munich).
      Study participation involves serial TSPO-PET imaging along with serial MR imaging, immune
      cell profiling in blood, and both clinical and laboratory assessments. Follow-up assessments
      at 3 weeks, 3 months, 6 months and 12 months will be conducted at the Institute for Stroke
      and Dementia Research (ISD) and at the Department of Nuclear medicine, both LMU Munich.

      In a substudy, the investigators will include 10 independently recruited patients with acute
      ischemic stroke to assess MRI arterial spin labelling (ASL) sequences as a marker for
      perfusion measurement of the TSPO tracer. These patients will receive dynamic PET in addition
      to the ASL sequences.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: 18 patients with cortical stroke and 18 patients with subcortical stroke
primary purpose: Basic Science
masking: None (Open Label)
measure: microglia activation in patients with acute stroke
time frame: within 10 days after acute ischemic stroke
description: Microglia activation will be assessed using TSPO PET imgaing.
measure: microglia activation in patients with acute stroke
time frame: 3 months after acute ischemic stroke
description: Microglia activation will be assessed using TSPO PET imgaing.
measure: functional outcome in patients after acute ischemic stroke
time frame: 3 weeks after acute ischemic stroke
description: Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.
measure: functional outcome in patients after acute ischemic stroke
time frame: 3 months after acute ischemic stroke
description: Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.
measure: functional outcome in patients after acute ischemic stroke
time frame: 6 months after acute ischemic stroke
description: Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.
measure: functional outcome in patients after acute ischemic stroke
time frame: 12 months after acute ischemic stroke
description: Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.
measure: cognitive outcome in patients after acute ischemic stroke
time frame: 3 weeks after acute ischemic stroke
description: Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.
measure: cognitive outcome in patients after acute ischemic stroke
time frame: 3 months after acute ischemic stroke
description: Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.
measure: cognitive outcome in patients after acute ischemic stroke
time frame: 6 months after acute ischemic stroke
description: Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.
measure: cognitive outcome in patients after acute ischemic stroke
time frame: 12 months after acute ischemic stroke
description: Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.
measure: inflammatory markers in blood
time frame: 3 weeks after acute ischemic stroke
description: Inflammatory markers in blood will be assessed by flow cytometry and related to microglial activation.
measure: inflammatory markers in blood
time frame: 3 months after acute ischemic stroke
description: Inflammatory markers in blood will be assessed by flow cytometry and related to microglial activation.
measure: Duplex ultrasound
time frame: 6 months after acute ischemic stroke
description: Duplex ultrasound will be performed to assess potential progress of atherosclerosis related to inflammatory markers
measure: 3T MR imaging
time frame: 3 months after acute ischemic stroke
description: 3T MRI will be performed to relate infarct evolution, secondary neurodegeneration, and stroke outcome to microglial activation.
measure: 3T MR imaging
time frame: 12 months after acute ischemic stroke
description: 3T MRI will be performed to relate infarct evolution, secondary neurodegeneration, and stroke outcome to microglial activation.
arm group label: TSPO PET imaging
arm group type: Other
description: All study participants will receive [18F]-GE-180, i.e. TSPO PET imaging to assess microglia activation.
intervention type: Diagnostic Test
intervention name: [18F]-GE-180 PET
description: serial [18F]-GE-180 PET imaging to assess microglia activation
arm group label: TSPO PET imaging
other name: TSPO PET imaging
intervention type: Diagnostic Test
intervention name: 3T MRI
description: serial MR imaging (i) to determine infarct characteristics, (ii) to identify gray and white matter structures connected to the infarct, (iii) to detect incident lesions, and (iv) to quantify longitudinal changes e.g. of cortical thickness
arm group label: TSPO PET imaging
intervention type: Diagnostic Test
intervention name: immune cell profiling in blood
description: Cell-specific cytokine profiles, markers of activation, terminal differentiation as well as cytotoxicity will be assesses using flow cytometry.
arm group label: TSPO PET imaging
criteria: 
gender: All
minimum age: 50 Years
maximum age: N/A
healthy volunteers: No
last name: Martin Dichgans, Prof.
role: Principal Investigator
affiliation: LMU Munich
last name: Peter Bartenstein, Prof.
role: Principal Investigator
affiliation: LMU Munich
last name: Sibylle Ziegler, Prof.
role: Principal Investigator
affiliation: LMU Munich
last name: Martin Dichgans, Prof.
phone: +49 4400
phone ext: 46019
email: martin.dichgans@med.uni-muenchen.de
last name: Anna Kopczak, MD
phone: +49 4400
phone ext: 46125
email: anna.kopczak@med.uni-muenchen.de
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
contact backup: 
country: Germany
responsible party type: Sponsor-Investigator
investigator affiliation: Ludwig-Maximilians - University of Munich
investigator full name: Martin Dichgans
investigator title: Prof. Dr. Martin Dichgans
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Cerebral Infarction
mesh term: Ischemia
sharing ipd: Undecided