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NCT Number: NCT04412187

Inflammatory faCtors AfteR acUte Ischemic Stroke

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.

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Key information

Age range

50 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Insitute for Stroke and Dementia Research, Munich, Germany

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

[18F]-GE-180 PET

Diagnostic Test

serial [18F]-GE-180 PET imaging to assess microglia activation

Other names: TSPO PET imaging

3T MRI

Diagnostic Test

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

immune cell profiling in blood

Diagnostic Test

Cell-specific cytokine profiles, markers of activation, terminal differentiation as well as cytotoxicity will be assesses using flow cytometry.

Primary outcomes

  1. microglia activation in patients with acute stroke

    Time frame: within 10 days 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 outcomes

  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. Duplex ultrasound

    Time frame: 6 months after acute ischemic stroke

    Duplex ultrasound will be performed to assess potential progress of atherosclerosis related to inflammatory markers

  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.

Study contacts

Contact information is provided by the study sponsor or research team.

Anna Kopczak, MD

CONTACT

[email protected]

+49 4400 ext. 46125

Martin Dichgans, Prof.

CONTACT

[email protected]

+49 4400 ext. 46019

Sponsors and collaborators

Lead sponsor

Martin Dichgans

Other

Collaborators

  • University Hospital Muenster
  • Universitätsklinikum Hamburg-Eppendorf

Registry information

Acronym: ICARUS

Important dates

Study start
2020
Primary completion
2026
Study completion
2027
First posted
Jun 2, 2020
Registry last updated
Apr 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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