Clinical trial NCT06121336: PRecisiOn Medicine In StrokE: Evolution of Plasma Brain-Derived Tau in Acute Stroke
Official title: PRecisiOn Medicine In StrokE Study on the Evolution of Plasma Brain-Derived Tau in 100 Patients With Acute Ischemic Stroke
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Stroke
Stroke, Acute
Stroke, Ischemic
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Brain Ischemia
Nervous System Diseases
Keywords: Stroke
Brain injury
Biomarker
Pathophysiology
Lead sponsor: Ludwig-Maximilians - University of Munich
Sponsor class: OTHER
First posted: 2023-11-07
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients will be recruited upon admission to a tertiary care hospital.

Brief summary: The investigators recently identified Brain-derived tau (BD-tau) as a sensitive blood-based biomarker for brain injury in acute ischemic stroke: in patients with acute ischemic stroke, plasma BD-tau was associated with imaging-based metrics of brain injury upon admission, increased within the first 24 hours in correlation with infarct progression, and at 24 hours was superior to final infarct volume in predicting 90-day functional outcome. While informing on the relation of BD-tau with imaging-based metrics of brain injury, this cross-sectional study was restricted to BD-tau assessments upon admission and at day 2 and could not inform on key characteristics of the evolution of plasma BD-tau, including when exactly it starts to rise, how long it continues to rise, and how it is determined by infarct characteristics as well as comorbidities. Here, the investigators aim to assess plasma BD-tau every hour from admission to 48 hours after onset to evaluate the hypothesis that BD-tau rises immediately after onset and plateaus between three and 48 hours after onset.

Detailed description: Ischemic stroke remains a leading cause of death and long-term disability worldwide,1 despite major advancements in reperfusion therapies.2,3 While neuroimaging modalities have expanded patient eligibility for reperfusion therapies by estimating ischemic core and salvageable tissue,4-7 their assessments are mostly single-timed. Currently available clinical algorithms lack the capacity to continuously track the dynamic evolution of how the primary core progresses to a final infarct, which, however, is a major determinant of functional outcome.8-10 Monitoring infarct trajectories could support therapeutic decision-making in patients with large-vessel occlusion stroke and unveil determinants of stroke progression, aiding in patient selection for trials evaluating cytoprotection11 and targeting clinically ineffective reperfusion.12 Previously studied blood-based biomarkers such as Neurofilament Light Chain (NfL),13 neuron-specific enolase (NSE),14 glial fibrillary acidic protein (GFAP),15,16 and S 100 calcium-binding protein B (S100B)17 either failed to capture the extent of brain injury within the acute phase of stroke or lack specificity. Plasma levels of brain-derived tau (BD-tau) were recently found to show high value for monitoring brain injury in patients with acute ischemic stroke: In 502 patients with acute IS, plasma BD-tau was associated with imaging-based metrics of brain injury upon admission, increased within the first 24 hours in correlation with infarct progression, and at 24 hours was superior to final infarct volume in predicting 90-day functional outcome.18 While informing on the relation of BD-tau with imaging-based metrics of brain injury, this large cross-sectional study was restricted to BD-tau assessments upon admission (median time from onset: 4.4 hours) and at day 2 (median time from onset: 22.7 hours) and could not inform on key characteristics of the evolution of plasma BD-tau, including when exactly it starts to rise, how long it continues to rise, and how it is determined by infarct characteristics as well as comorbidities. That knowledge would be of great value to determine the responsiveness of plasma BD-tau to brain injury after onset and to evaluate whether BD-tau plateaus at different time points after onset indicating no further infarct progression. Here, the investigators hypothesize that BD-tau rises immediately after onset and plateaus between three and 48 hours after onset. PROMISE-BD-100 will thus assess BD-tau levels every hour from admission to 48 hours from stroke onset in patients that present with the clinical diagnosis of an acute ischemic stroke due to a large- or medium-vessel occlusion within 9 hours from symptom onset.

Eligibility criteria: Inclusion Criteria:

* clinical diagnosis of acute ischemic stroke
* presentation within 9 hours of symptom onset
* large- or medium-vessel occlusion (i.e. an occlusion of the ICA, MCA \[segments M1-M4\], ACA \[segments A1-A3\], basilar artery, or PCA \[segments P1 to P3\]) confirmed by CT or MRI angiography
* at least 18 years of age
* written informed consent

Exclusion Criteria:

* CT or MRI showing intracranial hemorrhage upon admission
* A history of ischemic stroke, subarachnoid hemorrhage, intracerebral hemorrhage, subdural hematoma, epidural hematoma, CNS tumor, meningitis, or encephalitis within the last three months
* severe renal dysfunction (eGFR \< 30ml/min/1.73m2)
* dementia
* pre-stroke disability defined as a premorbid modified Rankin Scale score \> 1

Primary outcomes:
measure: The primary outcome are plasma BD-tau levels in acute ischemic stroke.
timeFrame: Every hour from admission to 48 hours after onset.
Secondary outcomes:
measure: ASPECTS on non-contrast CT
timeFrame: Upon admission
measure: Ischemic core volume on CT perfusion
timeFrame: Upon admission
measure: Regional leptomeningeal collateral score on CT angiography
timeFrame: Upon admission
measure: Final infarct volume
timeFrame: Between 48 hours after symptom onset and discharge (latest 10 days after onset)
measure: Infarct progression
timeFrame: Between admission and discharge (latest 10 days after onset)
measure: 90-day functional outcome
timeFrame: 90 days (± 14 days) after onset
measure: 7-day functional outcome
timeFrame: 7 days after onset
measure: Early recurrent ischemic stroke
timeFrame: Between admission and discharge (latest 10 days after onset)
measure: Secondary intracerebral hemorrhage
timeFrame: Between admission and discharge (latest 10 days after onset)
measure: Hemorrhagic transformation
timeFrame: Between admission and discharge (latest 10 days after onset)
Other outcomes:
measure: Plasma levels of NfL
timeFrame: Hourly from admission to 48 hours after onset
measure: Plasma levels of GFAP
timeFrame: Hourly from admission to 48 hours after onset
measure: Plasma proteome and metabolome composition
timeFrame: Hourly from admission to 48 hours after onset
Locations:
city: Munich
country: Germany
facility: LMU University hospital, LMU Munich
state: Bavaria
Study officials:
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