ICARUS: Inflammatory faCtors AfteR acUte Ischemic Stroke

Sponsor

Martin Dichgans (Other)

Overall Status

Recruiting

CT.gov ID

NCT04412187

Collaborator

Universitätsklinikum Hamburg-Eppendorf (Other), University Hospital Muenster (Other)

Enrollment

Locations

Arm

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

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	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

36 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

18 patients with cortical stroke and 18 patients with subcortical stroke18 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 :

Jul 1, 2020

Anticipated Primary Completion Date :

Nov 30, 2023

Anticipated Study Completion Date :

Nov 30, 2024

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

microglia activation in patients with acute stroke [within 10 days after acute ischemic stroke]
Microglia activation will be assessed using TSPO PET imgaing.
microglia activation in patients with acute stroke [3 months after acute ischemic stroke]
Microglia activation will be assessed using TSPO PET imgaing.
functional outcome in patients after acute ischemic stroke [3 weeks after acute ischemic stroke]
Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.
functional outcome in patients after acute ischemic stroke [3 months after acute ischemic stroke]
Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.
functional outcome in patients after acute ischemic stroke [6 months after acute ischemic stroke]
Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.
functional outcome in patients after acute ischemic stroke [12 months after acute ischemic stroke]
Functional outcome measured by the modified Rankin Score (mRS) will be assessed and related to microglial activation.
cognitive outcome in patients after acute ischemic stroke [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.
cognitive outcome in patients after acute ischemic stroke [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.
cognitive outcome in patients after acute ischemic stroke [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.
cognitive outcome in patients after acute ischemic stroke [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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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