Clinical trial NCT04412187: Inflammatory faCtors AfteR acUte Ischemic Stroke
Official title: Inflammatory faCtors AfteR acUte Ischemic Stroke
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ischemic Stroke
Keywords: microglia
neuroinflammation
functional outcome after stroke
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
Collaborators: name: Universitätsklinikum Hamburg-Eppendorf
name: University Hospital Muenster
First posted: 2020-06-02
Enrollment: 36
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: 18 patients with cortical stroke and 18 patients with subcortical stroke
Primary purpose: BASIC_SCIENCE

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.

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.

Eligibility 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

Primary outcomes:
measure: microglia activation in patients with acute stroke
timeFrame: within 10 days after acute ischemic stroke
measure: microglia activation in patients with acute stroke
timeFrame: 3 months after acute ischemic stroke
measure: functional outcome in patients after acute ischemic stroke
timeFrame: 3 weeks after acute ischemic stroke
measure: functional outcome in patients after acute ischemic stroke
timeFrame: 3 months after acute ischemic stroke
measure: functional outcome in patients after acute ischemic stroke
timeFrame: 6 months after acute ischemic stroke
measure: functional outcome in patients after acute ischemic stroke
timeFrame: 12 months after acute ischemic stroke
measure: cognitive outcome in patients after acute ischemic stroke
timeFrame: 3 weeks after acute ischemic stroke
measure: cognitive outcome in patients after acute ischemic stroke
timeFrame: 3 months after acute ischemic stroke
measure: cognitive outcome in patients after acute ischemic stroke
timeFrame: 6 months after acute ischemic stroke
measure: cognitive outcome in patients after acute ischemic stroke
timeFrame: 12 months after acute ischemic stroke
Secondary outcomes:
measure: inflammatory markers in blood
timeFrame: 3 weeks after acute ischemic stroke
measure: inflammatory markers in blood
timeFrame: 3 months after acute ischemic stroke
measure: Duplex ultrasound
timeFrame: 6 months after acute ischemic stroke
measure: 3T MR imaging
timeFrame: 3 months after acute ischemic stroke
measure: 3T MR imaging
timeFrame: 12 months after acute ischemic stroke
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Department of Nuclear Medicine
city: Munich
country: Germany
facility: Insitute for Stroke and Dementia Research
Study officials:
affiliation: LMU Munich
name: Martin Dichgans, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: LMU Munich
name: Peter Bartenstein, Prof.
role: PRINCIPAL_INVESTIGATOR
affiliation: LMU Munich
name: Sibylle Ziegler, Prof.
role: PRINCIPAL_INVESTIGATOR
References: