Wet and Dry Biomarkers to Predict Secondary Injury in Stroke: From Bench to Bedside - The NIMBLE Study

NCT07422636 | Completed

• 1 other identifier: CEAVC Studio 16606_oss
• Study Type: observational
• Target: 213
• Locations: 1 country
• Sites: 1

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.

Conditions

Acute Ischemic Stroke; Reperfusion Injury; Cerebral Edema; Hemorrhagic Transformation Due to Acute Stroke; Animal Model

Keywords

Anatomical Distortion; Blood biomarkes; Translational Stroke Research; Mouse ischemia/reperfusion stroke model; Ischemic Stroke; Brain Edema; Hemorrhagic Transformation; Cerebrovascular Disorders; Stroke Mouse Model

Outcome Measures

Primary Outcomes (2)

• Quantification of Anatomical Distortion (AD)

  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.

  From baseline imaging to CT and MRI scans follow up, performed respectively 1 and 5 days after stroke onset

• Infarct growth volume

  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.

  From baseline imaging to CT and MRI scans follow up, performed respectively 1 and 5 days after stroke onset.

Secondary Outcomes (1)

• Functional outcome

  Three months after stroke onset

Other Outcomes (5)

• Symptomatic Hemorrhagic Transformation

  From enrollment to 7 days after stroke onset.

• Cerebral Edema evaluated in with the animal model

  one day after stroke onset

• Hemorrhagic Transformation evaluated in with the animal model

  within one week after stroke onset

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

All patients with acute ischemic stroke, admitted directly to the Emergency Department of the Careggi University Hospital in the period between 04/24/2021 and 06/30/2023, who met the following inclusion criteria.

You may qualify if:

• 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;

You may not qualify if:

• 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;

Sponsors & Collaborators

• University of Florence: lead
• Careggi Hospital: collaborator
• Istituto di Neuroscienze Consiglio Nazionale delle Ricerche: collaborator

Study Sites (1)

University of Florence, NEUROFARBA Department, Careggi Hospital

Florence, Florence, 50134, Italy

Location

Related Publications (8)

• Simard JM, Kent TA, Chen M, Tarasov KV, Gerzanich V. Brain oedema in focal ischaemia: molecular pathophysiology and theoretical implications. Lancet Neurol. 2007 Mar;6(3):258-68. doi: 10.1016/S1474-4422(07)70055-8.

  PMID: 17303532 BACKGROUND

• Jickling GC, Liu D, Stamova B, Ander BP, Zhan X, Lu A, Sharp FR. Hemorrhagic transformation after ischemic stroke in animals and humans. J Cereb Blood Flow Metab. 2014 Feb;34(2):185-99. doi: 10.1038/jcbfm.2013.203. Epub 2013 Nov 27.

  PMID: 24281743 BACKGROUND

• Harston GWJ, Carone D, Sheerin F, Jenkinson M, Kennedy J. Quantifying Infarct Growth and Secondary Injury Volumes: Comparing Multimodal Image Registration Measures. Stroke. 2018 Jul;49(7):1647-1655. doi: 10.1161/STROKEAHA.118.020788. Epub 2018 Jun 12.

  PMID: 29895538 BACKGROUND

• Piccardi B, Biagini S, Iovene V, Palumbo V. Blood Biomarkers of Parenchymal Damage in Ischemic Stroke Patients Treated With Revascularization Therapies. Biomark Insights. 2019 Dec 24;14:1177271919888225. doi: 10.1177/1177271919888225. eCollection 2019.

  PMID: 31903021 BACKGROUND

• Allegra Mascaro AL, Conti E, Lai S, Di Giovanna AP, Spalletti C, Alia C, Panarese A, Scaglione A, Sacconi L, Micera S, Caleo M, Pavone FS. Combined Rehabilitation Promotes the Recovery of Structural and Functional Features of Healthy Neuronal Networks after Stroke. Cell Rep. 2019 Sep 24;28(13):3474-3485.e6. doi: 10.1016/j.celrep.2019.08.062.

  PMID: 31553915 BACKGROUND

• Conti E, Carlini N, Piccardi B, Allegra Mascaro AL, Pavone FS. Photothrombotic Middle Cerebral Artery Occlusion in Mice: A Novel Model of Ischemic Stroke. eNeuro. 2023 Feb 8;10(2):ENEURO.0244-22.2022. doi: 10.1523/ENEURO.0244-22.2022. Print 2023 Feb.

  PMID: 36650068 BACKGROUND

• Kenne E, Erlandsson A, Lindbom L, Hillered L, Clausen F. Neutrophil depletion reduces edema formation and tissue loss following traumatic brain injury in mice. J Neuroinflammation. 2012 Jan 23;9:17. doi: 10.1186/1742-2094-9-17.

  PMID: 22269349 BACKGROUND

• Nhan T, Burgess A, Cho EE, Stefanovic B, Lilge L, Hynynen K. Drug delivery to the brain by focused ultrasound induced blood-brain barrier disruption: quantitative evaluation of enhanced permeability of cerebral vasculature using two-photon microscopy. J Control Release. 2013 Nov 28;172(1):274-280. doi: 10.1016/j.jconrel.2013.08.029. Epub 2013 Sep 2.

  PMID: 24008151 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Patients blood will collected in tubes both with anticoagulant and without anticoagulant. Tubes will be then centrifuged at room temperature at 1500 x g for 15 minutes, and the supernatant is stored in aliquots at -80° C.

MeSH Terms

Conditions

Ischemic Stroke; Reperfusion Injury; Brain Edema; Disease Models, Animal; Cerebrovascular Disorders

Condition Hierarchy (Ancestors)

Stroke; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Animal Diseases

Study Officials

• Cristina Sarti, MD

  University of Florence, NEUROFARBA Department

  PRINCIPAL INVESTIGATOR

• Vanessa Palumbo, MD, PhD

  Careggi University Hospital

  STUDY DIRECTOR

• Benedetta Piccardi, MD, PhD

  Careggi University Hospital

  STUDY CHAIR

• Anna Letizia Allegra Mascaro, PhD

  Istituto di Neuroscienze Consiglio Nazionale delle Ricerche

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 3 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Neurologist and Clinical researcher

Study Record Dates

• First Submitted: November 18, 2025
• First Posted: February 20, 2026
• Study Start: April 17, 2021
• Primary Completion: December 31, 2023
• Study Completion: December 31, 2024
• Last Updated: February 20, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 3 months and ending 3 years after the publication of results.

Locations

IT (1)