Cerebral large vessel occlusion stroke multiomics biosample cohort (CLOMB): a multicentre cohort protocol
Zhiyuan Feng1,2, Ming Yang3, Jing Xue2
1Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Insights
This study establishes a protocol for biosampling the occlusion microenvironment in acute ischemic stroke with large vessel occlusion (AIS-LVO) patients undergoing endovascular treatment. It aims to identify markers for futile recanalization and improve stroke outcomes.
Area of Science:
- Neurology
- Biomarker Discovery
- Stroke Research
Background:
- Acute ischemic stroke with large vessel occlusion (AIS-LVO) requires endovascular treatment (EVT).
- Futile recanalization occurs in nearly 40% of AIS-LVO patients post-EVT.
- Understanding the occlusion microenvironment (OME) is crucial for identifying stroke markers.
Purpose of the Study:
- To establish a standardized protocol for OME biosampling and multiomics profiling in AIS-LVO patients.
- To explore candidate biological pathways associated with stroke and treatment outcomes.
- To lay the groundwork for hypothesis-generating models to improve AIS-LVO diagnosis, classification, and patient outcomes.
Main Methods:
- The Cerebral Large Vessel Occlusion Stroke Multiomics Biosample Cohort (CLOMB) study enrolled 500 AIS-LVO patients undergoing EVT across five Chinese stroke centers.
- Collected biosamples include peripheral blood, thrombus, and intracranial blood from the occlusion site.
- Multi-omics analyses (metabolomic, proteomic, transcriptomic) were performed, with single-cell RNA sequencing on a subset.
Main Results:
- A standardized protocol for OME biosampling and multiomics profiling was successfully established.
- The study collected comprehensive clinical and multi-omics data from AIS-LVO patients.
- Analysis is ongoing to identify biological pathways and candidate biomarkers.
Conclusions:
- The CLOMB study provides a robust framework for OME research in AIS-LVO.
- This multiomics approach facilitates the discovery of novel biomarkers and pathways.
- The findings will support the development of improved diagnostic and therapeutic strategies for AIS-LVO.
Background:
Acute ischaemic stroke with large vessel occlusion (AIS-LVO) is a significant subtype of ischaemic stroke which always requires endovascular treatment (EVT). Although EVT has a high recanalisation rate, nearly 40% of AIS-LVO patients experience futile recanalisation. Studying the occlusion microenvironment (OME), comprising thrombus and intracranial arterial blood, is essential to understand the localised markers of stroke and futile recanalisation.
Design:
Cerebral Large Vessel Occlusion Stroke Multiomics Biosample Cohort (CLOMB) is a multicentre, multiomics ambispective cohort study conducted in five stroke centres in China. A total of 500 patients with AIS-LVO who undergo EVT will be included in the study. After enrolment, each participant undergoes a comprehensive clinical assessment including questionnaires, physical examinations, laboratory tests and imaging. We collect matched peripheral (arterial and venous) blood, thrombus and innovatively intracranial blood by microcatheter or aspiration catheter when first passing through the occlusion site. All biosamples are collected for subsequent multi-omics analysis (metabolomic, proteomic and transcriptomic). A 3-month and 1-year follow-up will be performed to collect the outcome data.
Methods:
Systemic and local samples undergo untargeted metabolomic and proteomic analysis. For a representative subset (10%-15%), single-cell RNA sequencing (Switching Mechanism at 5' End of the RNA Transcript) is performed. Targeted omics will be selectively implemented to further clarify their contents. To minimise selection bias, patients without retrieved thrombi remain in the cohort for clinical analysis.
Conclusion:
CLOMB establishes a standardised protocol for OME biosampling and multiomics profiling. It aims to explore candidate biological pathways and provide a foundation for developing hypothesis-generating models for improving stroke outcomes, facilitating AIS-LVO diagnosis and classification.
Trial Registration Number:
NCT06963489.
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