Inflammatory faCtors AfteR acUte Ischemic Stroke

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест [18F]-GE-180 PET
  serial \[18F\]-GE-180 PET imaging to assess microglia activation
• Диагностический тест 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
• Диагностический тест immune cell profiling in blood
  Cell-specific cytokine profiles, markers of activation, terminal differentiation as well as cytotoxicity will be assesses using flow cytometry.

Первичные конечные точки

• microglia activation in patients with acute stroke [Срок оценки: within 10 days after acute ischemic stroke]
• microglia activation in patients with acute stroke [Срок оценки: 3 months after acute ischemic stroke]
• functional outcome in patients after acute ischemic stroke [Срок оценки: 3 weeks after acute ischemic stroke]
• functional outcome in patients after acute ischemic stroke [Срок оценки: 3 months after acute ischemic stroke]
• functional outcome in patients after acute ischemic stroke [Срок оценки: 6 months after acute ischemic stroke]
• functional outcome in patients after acute ischemic stroke [Срок оценки: 12 months after acute ischemic stroke]
• cognitive outcome in patients after acute ischemic stroke [Срок оценки: 3 weeks after acute ischemic stroke]
• cognitive outcome in patients after acute ischemic stroke [Срок оценки: 3 months after acute ischemic stroke]
• cognitive outcome in patients after acute ischemic stroke [Срок оценки: 6 months after acute ischemic stroke]
• cognitive outcome in patients after acute ischemic stroke [Срок оценки: 12 months after acute ischemic stroke]

Вторичные конечные точки (5)

• inflammatory markers in blood [Срок оценки: 3 weeks after acute ischemic stroke]
• inflammatory markers in blood [Срок оценки: 3 months after acute ischemic stroke]
• Duplex ultrasound [Срок оценки: 6 months after acute ischemic stroke]
• 3T MR imaging [Срок оценки: 3 months after acute ischemic stroke]
• 3T MR imaging [Срок оценки: 12 months after acute ischemic stroke]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Германия · 2 центра

• Insitute for Stroke and Dementia Research — Munich
• Department of Nuclear Medicine — Munich

Идентификаторы

NCT: NCT04412187 · 19-428

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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