Integrating Novel NeuroImaging Measurements and Circulating Biomarkers for the Prediction of Secondary Injury foLlowing strokE: From Bench to Bedside - The NIMBLE Study (NIMBLE)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- University of Florence
- Enrollment
- 213
- Locations
- 1
- Primary Endpoint
- Quantification of Anatomical Distortion (AD)
Study Overview
Brief Summary
Infarct growth (IG), Hemorrhagic Transformation (HT) and Cerebral Edema (CE) can be considered pivotal phenomena of clinical deterioration following an acute ischemic stroke. Innovative techniques applied to neuroimaging allow these phenomena to be identified and measured more adequately than techniques and approaches commonly in use. Some circulating molecules are conceptually usable as biological markers of CE, HT, and IG. The correlation between circulating and neuroimaging biomarkers, and the investigation of neuronal structural remodeling induced by ischemia, may provide fundamental details to prevent or contrast clinical deterioration after ischemic stroke. To achieve this goal, the investigators planned to perform translational research on humans and on a novel mouse model of ischemic stroke.
More specifically, the investigators planned a clinical prospective observational study on a consecutive series of patients with acute anterior ischemic stroke either submitted or not submitted to revascularization therapies. Serum levels of several blood biomarkers related to inflammation, blood-brain barrier disruption, and reperfusion injury are analyzed in relation to CE, HT, IG, and final infarct volume, evaluated on CT/MRI images, and to 3 months functional status evaluated by the modified Rankin Scale.
In parallel, the investigators employ a newly developed experimental model of stroke and recanalization of the distal branch of the middle cerebral artery in mice to study, with advanced optical imaging techniques, the structural reorganization of neurons at the cellular and subcellular level in relation with the blood vessel extravasation (CE) and with the levels of circulating biomarkers at different time points after stroke.
The investigators will verify to what extent the animal model can reliably reproduce significant parameters that are evaluated in stroke patients, i.e. circulating biomarkers levels in relation to lesion volume and edema formation. Once validated, the data on the structural plasticity of mice shall be used to infer the mechanisms that determine the clinical deterioration due to IG, HT, and CE.
Detailed Description
BACKGROUND Infarct growth (IG), Hemorrhagic Transformation (HT), and Cerebral Edema (CE) are key factors associated with a negative outcome in ischemic stroke patients, despite the success of recanalization. Futile reperfusion and reperfusion injury are linked to these harmful phenomena but their mechanisms remain largely not understood and consequently they are difficult to be predicted and hindered. Various studies have shown that some circulating biomarkers are associated with the development of IG, HT, and CE.
The NIMBLE Study (Integrating novel NeuroImaging Measurements and circulating Biomarkers for the prediction of secondary injury foLlowing strokE: from bench to bedside) is a translational project including clinical research in humans and experimental study in animals. It has the aim to investigate possible factors contributing to IG, HT, and CE after ischemia by studying circulating biomarkers in respect to neuroimaging abnormalities and functional outcome in humans. In mice circulating biomarkers are studied in respect to the neuronal reorganization at the cellular and subcellular level and to experimental evaluation of CE.
CLINICAL SETTING
Study design:
Single-centre, longitudinal, follow-up prospective observational study enrolling a consecutive series of patients, with anterior acute ischemic stroke presenting within 12 hours from symptom onset to the Emergency Department either treated or not treated with revascularization therapies.
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Prospective
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Acute ischemic stroke;
- •Anterior Circulation stroke (TACS, PACS, LACS according Bamford classification);
- •Age ≥ 18 years;
- •Onset of symptoms within 12 hours;
- •Providing informed consent to data processing;
Exclusion Criteria
- •Diagnosis of haemorrhagic stroke;
- •Baseline and follow-up clinical and radiological parameters consistent with posterior circulation stroke;
- •Admission beyond 12 hours from symptoms onset;
- •Patients transferred from other hospitals or with in-hospital onset;
- •Patients denying or withdrawing their consent to data processing;
- •Pregnancy;
Outcomes
Primary Outcomes
Quantification of Anatomical Distortion (AD)
Time Frame: From baseline imaging to CT and MRI scans follow up, performed respectively 1 and 5 days after stroke onset
The application of an experimental method aimed at identifying the presence of AD (and measure its volume in milliliters \[mL\]) induced in the brain tissue by cerebral edema and hemorrhagic transformation, allows to quantify the extent of these two phenomena and to highlight the actual growth of the lesion volume beyond the extravasation of liquids in the brain tissue.
Infarct growth volume
Time Frame: From baseline imaging to CT and MRI scans follow up, performed respectively 1 and 5 days after stroke onset.
Infarct growth is measured (in milliliters \[mL\]) by comparing ischemic core volumes in CT Perfusion at baseline to lesion volumes in CT and MRI at 1 and 5 days after stroke onset, respectively, and by comparing lesion volumes obtained from CT and MRI at 1 and 5 days after stroke onset in the same patients.
Secondary Outcomes
- Functional outcome(Three months after stroke onset)
Investigators
Cristina Sarti
Principal Investigator, Neurologist and Clinical researcher
University of Florence