Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Inflammatory faCtors AfteR acUte Ischemic Stroke (ICARUS)

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 evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04412187
Recruitment Status : Recruiting
First Posted : June 2, 2020
Last Update Posted : October 5, 2020
Sponsor:
Collaborators:
Universitätsklinikum Hamburg-Eppendorf
University Hospital Muenster
Information provided by (Responsible Party):
Martin Dichgans, Ludwig-Maximilians - University of Munich

Brief Summary:

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.


Condition or disease Intervention/treatment Phase
Ischemic Stroke Diagnostic Test: [18F]-GE-180 PET Diagnostic Test: 3T MRI Diagnostic Test: immune cell profiling in blood Not Applicable

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 36 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: 18 patients with cortical stroke and 18 patients with subcortical stroke
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Inflammatory faCtors AfteR acUte Ischemic Stroke
Actual Study Start Date : July 1, 2020
Estimated Primary Completion Date : November 30, 2023
Estimated Study Completion Date : November 30, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
TSPO PET imaging
All study participants will receive [18F]-GE-180, i.e. TSPO PET imaging to assess microglia activation.
Diagnostic Test: [18F]-GE-180 PET
serial [18F]-GE-180 PET imaging to assess microglia activation
Other Name: TSPO PET imaging

Diagnostic Test: 3T MRI
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

Diagnostic Test: immune cell profiling in blood
Cell-specific cytokine profiles, markers of activation, terminal differentiation as well as cytotoxicity will be assesses using flow cytometry.




Primary Outcome Measures :
  1. microglia activation in patients with acute stroke [ Time Frame: 3 weeks after acute ischemic stroke ]
    Microglia activation will be assessed using TSPO PET imgaing.

  2. microglia activation in patients with acute stroke [ Time Frame: 3 months after acute ischemic stroke ]
    Microglia activation will be assessed using TSPO PET imgaing.

  3. functional outcome in patients after acute ischemic stroke [ Time Frame: 3 weeks after acute ischemic stroke ]
    Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.

  4. functional outcome in patients after acute ischemic stroke [ Time Frame: 3 months after acute ischemic stroke ]
    Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.

  5. functional outcome in patients after acute ischemic stroke [ Time Frame: 6 months after acute ischemic stroke ]
    Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.

  6. functional outcome in patients after acute ischemic stroke [ Time Frame: 12 months after acute ischemic stroke ]
    Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.

  7. cognitive outcome in patients after acute ischemic stroke [ Time Frame: 3 weeks after acute ischemic stroke ]
    Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.

  8. cognitive outcome in patients after acute ischemic stroke [ Time Frame: 3 months after acute ischemic stroke ]
    Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.

  9. cognitive outcome in patients after acute ischemic stroke [ Time Frame: 6 months after acute ischemic stroke ]
    Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.

  10. cognitive outcome in patients after acute ischemic stroke [ Time Frame: 12 months after acute ischemic stroke ]
    Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.


Secondary Outcome Measures :
  1. inflammatory markers in blood [ Time Frame: 3 weeks after acute ischemic stroke ]
    Inflammatory markers in blood will be assessed by flow cytometry and related to microglial activation.

  2. inflammatory markers in blood [ Time Frame: 3 months after acute ischemic stroke ]
    Inflammatory markers in blood will be assessed by flow cytometry and related to microglial activation.

  3. 3T MR imaging [ Time Frame: 3 weeks after acute ischemic stroke ]
    3T MRI will be performed to relate infarct evolution, secondary neurodegeneration, and stroke outcome to microglial activation.

  4. 3T MR imaging [ Time Frame: 3 months after acute ischemic stroke ]
    3T MRI will be performed to relate infarct evolution, secondary neurodegeneration, and stroke outcome to microglial activation.

  5. 3T MR imaging [ Time Frame: 12 months after acute ischemic stroke ]
    3T MRI will be performed to relate infarct evolution, secondary neurodegeneration, and stroke outcome to microglial activation.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 50 years
  • Acute ischemic stroke (time frame: <72 hours) as defined by an acute focal neurological deficit in combination with a corresponding infarct as documented by a diffusion weighted imaging (DWI)-positive lesion on magnetic resonance imaging (MRI); presence of an infarct involving the cortex or a strictly subcortical infarct
  • Written informed consent prior to study participation
  • Willingness to participate in study assessments including follow-up

Exclusion Criteria:

  • Unwillingness or inability to give written consent
  • Prior history of stroke, multiple infarcts, infratentorial infarcts affecting the brain stem or cerebellum
  • Known diseases of the CNS other than stroke
  • Immunomodulatory therapies within the last 3 months prior stroke
  • Chronic inflammatory disease
  • Infectious diseases within the last 7 days prior stroke
  • Conditions interfering with follow-up such as end-stage malignancy
  • Contraindications for MRI or PET (pacemaker, aneurysm clip, cochlear implant etc.)
  • Radiation exposure of > 10mSv per year
  • Pregnant or breastfeeding women
  • Participation in a clinical trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04412187


Contacts
Layout table for location contacts
Contact: Martin Dichgans, Prof. +49 4400 ext 46019 martin.dichgans@med.uni-muenchen.de
Contact: Anna Kopczak, MD +49 4400 ext 46125 anna.kopczak@med.uni-muenchen.de

Locations
Layout table for location information
Germany
Department of Nuclear Medicine Not yet recruiting
Munich, Germany, 81377
Contact: Peter Bartenstein, Prof.    +49 89 4400 ext 77646    peter.bartenstein@med.uni-muenchen.de   
Contact: Matthias Brendel, MD    +49 89 4400 ext 74646    matthias.brendel@med.uni-muenchen.de   
Insitute for Stroke and Dementia Research Recruiting
Munich, Germany, 81377
Contact: Martin Dichgans, Prof.    +49 89 4400 ext 46019      
Contact: Anna Kopczak, MD    +49 89 4400 ext 46125      
Sponsors and Collaborators
Martin Dichgans
Universitätsklinikum Hamburg-Eppendorf
University Hospital Muenster
Investigators
Layout table for investigator information
Principal Investigator: Martin Dichgans, Prof. LMU Munich
Principal Investigator: Peter Bartenstein, Prof. LMU Munich
Principal Investigator: Sibylle Ziegler, Prof. LMU Munich
Layout table for additonal information
Responsible Party: Martin Dichgans, Prof. Dr. Martin Dichgans, Ludwig-Maximilians - University of Munich
ClinicalTrials.gov Identifier: NCT04412187    
Other Study ID Numbers: 19-428
First Posted: June 2, 2020    Key Record Dates
Last Update Posted: October 5, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Martin Dichgans, Ludwig-Maximilians - University of Munich:
microglia
neuroinflammation
functional outcome after stroke
Additional relevant MeSH terms:
Layout table for MeSH terms
Stroke
Cerebral Infarction
Ischemia
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Vascular Diseases
Cardiovascular Diseases
Pathologic Processes
Brain Infarction
Brain Ischemia