Microclots and Neutrophil Activation as Potential Indicators for Stroke Risk and Reperfusion Failure
NCT ID: NCT06530927
Last Updated: 2025-08-29
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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RECRUITING
500 participants
OBSERVATIONAL
2025-02-01
2030-12-01
Brief Summary
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Detailed Description
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Stroke remains a major health burden worldwide. Many patients are severely disabled and stay in need of care. Since introducing mechanical thrombectomy as a therapeutic option, clinical outcome has drastically improved over the last few years. However, despite successful macrovascular reperfusion (recanalization), patients with stroke still have a significant risk (about 40-50%) of remaining severely disabled, a scenario called "futile recanalization". One of the causes for this lack of treatment effect is capillary obstruction, or "no reflow", potentially resulting from activated neutrophils and micrometer-sized blood clots. Previous work in rodent stroke models demonstrated that removal of these capillary stalls indeed improves reperfusion and recovery after stroke. However, there is a lack of knowledge regarding the role of neutrophils or microclots in patients with stroke, and their potential to indicate reperfusion failure.
Aim:
The goal of our study is to search for activated neutrophils and microclots in peripheral blood samples from patients with stroke. We anticipate that neutrophil and microclot characteristics such as size, shape, or surface structure may indicate stroke risk, and may be associated with clinical outcome, stroke ethology and reperfusion failure in patients with stroke. Our goal is to improve the prediction of stroke risk and treatment success.
Methodology:
We plan to prospectively include 500 patients with acute and chronic stroke, as well as a control group. We have teamed up with biophysicists from the Swiss Federal Laboratories for Materials Science (EMPA) using the novel microscopic tools 3D rotational digital tomography (DHTM) to achieve an unprecedented resolution of less than 10 μm for detection of altered neutrophil phenotypes and microclots in peripheral blood samples. Furthermore, in patients undergoing mechanical thrombectomy, retrieved clots will be analyzed with high-density micro-computertomography (micro-CT). Quantity, mechanical and structural properties of microclots and neutrophils will be correlated with risk of reperfusion failure, stroke recurrence and clinical recovery. Analyses of clots from patients with large vessel occlusion will be used to derive risk of reperfusion failure along with most likely source of the clot, and thus, most likely stroke etiology.
Potential Significance:
Current diagnostic tools are insufficient to predict response to treatment, clot source or stroke recurrence risk. Our project has the potential to discover new, clinically applicable biomarkers identifying patients at risk within a few hours, enabling individualized stroke treatment and prevention.
Conditions
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Study Design
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COHORT
PROSPECTIVE
Study Groups
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Control Group
Patients without previous documented stroke
3D rotational digital tomography
DHTM is label-free and records the phase shift of low-energy light passing through the specimen on a transparent surface with minimal perturbation. DHTM measures the refractive index (RI) and computes the refractive index gradient (RIG), unveiling optical heterogeneity in cells. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots.
Atomic Force Microscopy
The atomic force microscope (AFM) is widely used in materials science and has found many applications in biological sciences but has been limited in use in vision science. The AFM can be used to image the topography of soft biological materials in their native environments. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots
Chronic Stroke Group
Patients with previous stroke ≥1year ago
3D rotational digital tomography
DHTM is label-free and records the phase shift of low-energy light passing through the specimen on a transparent surface with minimal perturbation. DHTM measures the refractive index (RI) and computes the refractive index gradient (RIG), unveiling optical heterogeneity in cells. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots.
Atomic Force Microscopy
The atomic force microscope (AFM) is widely used in materials science and has found many applications in biological sciences but has been limited in use in vision science. The AFM can be used to image the topography of soft biological materials in their native environments. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots
Acute Stroke No Therapy Group
Patients with acute stroke, but without intravenous thrombolysis or mechanical thrombectomy
3D rotational digital tomography
DHTM is label-free and records the phase shift of low-energy light passing through the specimen on a transparent surface with minimal perturbation. DHTM measures the refractive index (RI) and computes the refractive index gradient (RIG), unveiling optical heterogeneity in cells. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots.
Atomic Force Microscopy
The atomic force microscope (AFM) is widely used in materials science and has found many applications in biological sciences but has been limited in use in vision science. The AFM can be used to image the topography of soft biological materials in their native environments. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots
Acute Stroke IVT only Group
Patients with acute stroke and intravenous thrombolysis
3D rotational digital tomography
DHTM is label-free and records the phase shift of low-energy light passing through the specimen on a transparent surface with minimal perturbation. DHTM measures the refractive index (RI) and computes the refractive index gradient (RIG), unveiling optical heterogeneity in cells. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots.
Atomic Force Microscopy
The atomic force microscope (AFM) is widely used in materials science and has found many applications in biological sciences but has been limited in use in vision science. The AFM can be used to image the topography of soft biological materials in their native environments. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots
Acute Stroke MT-Group
Patients with acute stroke and mechanical thrombectomy
3D rotational digital tomography
DHTM is label-free and records the phase shift of low-energy light passing through the specimen on a transparent surface with minimal perturbation. DHTM measures the refractive index (RI) and computes the refractive index gradient (RIG), unveiling optical heterogeneity in cells. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots.
Atomic Force Microscopy
The atomic force microscope (AFM) is widely used in materials science and has found many applications in biological sciences but has been limited in use in vision science. The AFM can be used to image the topography of soft biological materials in their native environments. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots
Micro-Computertomography
Micro-CT is a 3D imaging technique utilizing X-rays to see inside an object, slice by slice. Micro-CT, also called microtomography or micro computed tomography, is similar to hospital CT or "CAT" scan imaging but on a small scale with greatly increased resolution. Samples can be imaged with pixel sizes as small as 100 nanometers and objects can be scanned as large as 200 millimeters in diameter. We will use micro-CT to analyze blood clots from patients with large vessel occlusion.
Interventions
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3D rotational digital tomography
DHTM is label-free and records the phase shift of low-energy light passing through the specimen on a transparent surface with minimal perturbation. DHTM measures the refractive index (RI) and computes the refractive index gradient (RIG), unveiling optical heterogeneity in cells. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots.
Atomic Force Microscopy
The atomic force microscope (AFM) is widely used in materials science and has found many applications in biological sciences but has been limited in use in vision science. The AFM can be used to image the topography of soft biological materials in their native environments. We will analyze blood samples for the detection of altered neutrophil phenotypes and microclots
Micro-Computertomography
Micro-CT is a 3D imaging technique utilizing X-rays to see inside an object, slice by slice. Micro-CT, also called microtomography or micro computed tomography, is similar to hospital CT or "CAT" scan imaging but on a small scale with greatly increased resolution. Samples can be imaged with pixel sizes as small as 100 nanometers and objects can be scanned as large as 200 millimeters in diameter. We will use micro-CT to analyze blood clots from patients with large vessel occlusion.
Eligibility Criteria
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Inclusion Criteria
* No previous stroke or previous stroke ≥ 1 year ago
* Signed informed consent
Patients with acute stroke (AS-noTx, AS-IVT, AS-MT):
* Patients admitted with high suspicion of acute ischemic stroke
* Time of onset of stroke symptoms ≤ 12 hours
* Consent according to the regulations of research in an emergency situation
* Ischemic stroke later confirmed
Exclusion Criteria
* Pregnancy
* Age under 18 years
Acute Stroke no Therapy
• Acute treatment with IVT or with MT
Acute Stroke IVT-Group • Acute treatment with MT or without IVT
Acute Stroke MT-Group
• Acute treatment without MT
18 Years
ALL
Yes
Sponsors
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Empa, Swiss Federal Laboratories for Materials Science and Technology
OTHER
University of Zurich
OTHER
Responsible Party
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Susanne Wegener
Prof. Dr. med.
Principal Investigators
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Susanne Wegener, Prof.
Role: PRINCIPAL_INVESTIGATOR
University Hospital Zurich, department Neurology
Locations
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University Hospital Zurich
Zurich, Canton of Zurich, Switzerland
Countries
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Central Contacts
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Facility Contacts
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Other Identifiers
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2024-01353
Identifier Type: -
Identifier Source: org_study_id
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