Characterization of the Blood-Brain Barrier in High-Grade Glioma Through Immunohistochemical, Transcriptional, Fluorescein and Radiological Analyses
Trial Snapshot
- Phase
- Not Applicable
- Status
- Recruiting
- Sponsor
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- Serum Biomarkers of Blood-Brain Barrier Disruption and Neuronal Injury
Study Overview
Brief Summary
This prospective study aims to characterize blood brain barrier (BBB) disruption in patients with newly diagnosed glioblastoma multiforme undergoing surgical resection. The study integrates advanced MRI, circulating BBB biomarkers, neurocognitive assessment, and molecular analysis of tumor tissue to investigate relationships between BBB integrity, tumor biology, and neurological function. Participants will undergo serial assessments before surgery, after surgery, and following radiotherapy. Tumor tissue collected during standard-of-care resection will undergo immunohistochemical and transcriptional
Detailed Description
Glioblastoma is characterized by disruption of the blood-brain barrier, which may influence tumor progression, neurological dysfunction, treatment delivery, and clinical outcomes. This study seeks to comprehensively characterize BBB integrity using multimodal approaches.
Participants with newly diagnosed GBM selected for surgical resection will undergo:
- Clinical and demographic data collection.
- Neurocognitive assessment using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) and Reading the Mind in the Eyes Test (RMET).
- High-resolution 3-Tesla MRI with and without gadolinium contrast, including structural and functional imaging sequences.
- Blood sampling for measurement of biomarkers associated with BBB disruption and neuronal injury, including S100β, GFAP, UCHL1, amyloid beta, phosphorylated tau, and neuron-specific enolase.
- Collection of tumor tissue during routine surgical resection for immunohistochemical and transcriptional analyses.
Serial evaluations will be performed preoperatively, postoperatively, at 72 hours, at 4 weeks, and 4 weeks following completion of radiotherapy, according to the assessment schedule.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Diagnostic
- Masking
- None
Masking Description
Participants with newly diagnosed glioblastoma will undergo a standardized multimodal assessment program including advanced MRI imaging, serial blood biomarker sampling, neurocognitive testing, and molecular characterization of tumor tissue obtained during surgical resection. Assessments will be performed longitudinally before and after surgery and following completion of radiotherapy.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Adult patients aged 18 years or older.
- •Newly diagnosed glioblastoma.
- •Selected for surgical tumor resection.
- •Able and willing to provide written informed consent.
- •Able to undergo study assessments and follow-up procedures.
Exclusion Criteria
- •Contraindication to magnetic resonance imaging.
- •Confusion, delirium, or altered state of consciousness that interferes with the ability to provide informed consent.
- •Any condition that, in the opinion of the investigator, would prevent completion of study procedures or compromise participant safety.
Outcomes
Primary Outcomes
Serum Biomarkers of Blood-Brain Barrier Disruption and Neuronal Injury
Time Frame: Baseline (within 7 days before surgery), intraoperative, within 24 hours after surgery, 72 hours after surgery, 4 weeks after surgery, and 4 weeks after completion of radiotherapy
Serial measurement of serum biomarkers associated with blood-brain barrier disruption and neuronal injury, including S100β, GFAP, UCHL1, amyloid beta, phosphorylated tau, and neuron-specific enolase. Biomarker concentrations will be assessed longitudinally to characterize changes in blood-brain barrier integrity in patients with newly diagnosed glioblastoma undergoing surgical resection and radiotherapy.
Secondary Outcomes
- MRI Based Measures of Blood-Brain Barrier Integrity(4 weeks after surgery)
- Immunohistochemical Characterisation of Blood-Brain Barrier Disruption(During surgical resection (single assessment))
- Transcriptional Characterisation of Blood-Brain Barrier Disruption(During surgical resection (single assessment))
- Neurocognitive Function Assessed by RBANS(Baseline (within 7 days before surgery), 4 weeks after surgery, and 4 weeks after completion of radiotherapy)
Investigators
Patrick Morris
Clinical Director Cancer Clinical Trials Unit
Beaumont Hospital