Inflammatory faCtors AfteR acUte Ischemic Stroke (ICARUS)

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.

Study Overview

• Status: Recruiting
• Conditions: Ischemic Stroke
• Intervention / Treatment: Diagnostic test: [18F]-GE-180 PET; Diagnostic test: 3T MRI; Diagnostic test: immune cell profiling in blood

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.

• Study Type: Interventional
• Enrollment (Estimated): 36
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Martin Dichgans, Prof.; Phone Number: 46019 +49 4400; Email: martin.dichgans@med.uni-muenchen.de
• Study Contact Backup: Name: Anna Kopczak, MD; Phone Number: 46125 +49 4400; Email: anna.kopczak@med.uni-muenchen.de

Study Locations

• Germany
  • Munich, Germany, 81377
    • Recruiting
    • Insitute for Stroke and Dementia Research
    • Contact: Martin Dichgans, Prof.; Phone Number: 46019 +49 89 4400
    • Contact: Anna Kopczak, MD; Phone Number: 46125 +49 89 4400
  • Munich, Germany, 81377
    • Recruiting
    • Department of Nuclear Medicine
    • Contact: Peter Bartenstein, Prof.; Phone Number: 77646 +49 89 4400; Email: peter.bartenstein@med.uni-muenchen.de
    • Contact: Matthias Brendel, MD; Phone Number: 74646 +49 89 4400; Email: matthias.brendel@med.uni-muenchen.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
microglia activation in patients with acute stroke	Microglia activation will be assessed using TSPO PET imgaing.	within 10 days after acute ischemic stroke
microglia activation in patients with acute stroke	Microglia activation will be assessed using TSPO PET imgaing.	3 months after acute ischemic stroke
functional outcome in patients after acute ischemic stroke	Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.	3 weeks after acute ischemic stroke
functional outcome in patients after acute ischemic stroke	Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.	3 months after acute ischemic stroke
functional outcome in patients after acute ischemic stroke	Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.	6 months after acute ischemic stroke
functional outcome in patients after acute ischemic stroke	Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.	12 months after acute ischemic stroke
cognitive outcome in patients after acute ischemic stroke	Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.	3 weeks after acute ischemic stroke
cognitive outcome in patients after acute ischemic stroke	Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.	3 months after acute ischemic stroke
cognitive outcome in patients after acute ischemic stroke	Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.	6 months after acute ischemic stroke
cognitive outcome in patients after acute ischemic stroke	Functional outcome in terms of cognition will be assessed by the Montreal Cognitive Assessment (MoCA) and related to microglial activation.	12 months after acute ischemic stroke

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
inflammatory markers in blood	Inflammatory markers in blood will be assessed by flow cytometry and related to microglial activation.	3 weeks after acute ischemic stroke
inflammatory markers in blood	Inflammatory markers in blood will be assessed by flow cytometry and related to microglial activation.	3 months after acute ischemic stroke
Duplex ultrasound	Duplex ultrasound will be performed to assess potential progress of atherosclerosis related to inflammatory markers	6 months after acute ischemic stroke
3T MR imaging	3T MRI will be performed to relate infarct evolution, secondary neurodegeneration, and stroke outcome to microglial activation.	3 months after acute ischemic stroke
3T MR imaging	3T MRI will be performed to relate infarct evolution, secondary neurodegeneration, and stroke outcome to microglial activation.	12 months after acute ischemic stroke

Collaborators and Investigators

• Sponsor: Martin Dichgans
• Collaborators: University Hospital Muenster; Universitätsklinikum Hamburg-Eppendorf
• Investigators: Principal Investigator: Martin Dichgans, Prof., LMU Munich; Principal Investigator: Peter Bartenstein, Prof., LMU Munich; Principal Investigator: Sibylle Ziegler, Prof., LMU Munich

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2025

Study Registration Dates

• First Submitted: May 22, 2020
• First Submitted That Met QC Criteria: May 28, 2020
• First Posted (Actual): June 2, 2020

Study Record Updates

• Last Update Posted (Actual): March 19, 2024
• Last Update Submitted That Met QC Criteria: March 18, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: microglia; neuroinflammation; functional outcome after stroke
• Additional Relevant MeSH Terms: Pathologic Processes; Necrosis; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Brain Ischemia; Infarction; Brain Infarction; Stroke; Ischemic Stroke; Ischemia; Cerebral Infarction
• Other Study ID Numbers: 19-428

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No