Glioblastoma
Conditions
Keywords
Blood Brain Barrier, Glioblastoma, High Grade Glioma
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.
Interventions
DIAGNOSTIC_TESTMultimodal Blood Brain Barrier Assessment
A standardised multimodal diagnostic assessment designed to characterize blood brain barrier integrity in patients with newly diagnosed glioblastoma. The intervention includes advanced contrast enhanced MRI, serial blood sampling for measurement of blood-brain barrier and neuronal injury biomarkers (including S100β, GFAP, UCHL1, amyloid beta, phosphorylated tau, and neuron-specific enolase), neurocognitive assessments, and immunohistochemical and transcriptional analyses of tumor tissue obtained during standard-of-care surgical resection. Assessments are performed longitudinally before surgery, after surgery, at 72 hours, at 4 weeks, and following completion of radiotherapy.
Sponsors
Patrick Morris
Study design
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.
Intervention model description
Phase 2, single-arm, open label interventional study designed to evaluate blood-brain barrier (BBB) disruption in patients with newly diagnosed glioblastoma. All participants will undergo a standardized intervention schedule consisting of advanced contrast-enhanced MRI, serial blood biomarker assessments, neurocognitive testing, and tumor tissue collection and analysis in conjunction with standard-of-care surgical resection and subsequent treatment. The study will evaluate longitudinal changes in BBB integrity and their association with radiological, molecular, and neurocognitive outcomes across multiple predefined time points from diagnosis through completion of radiotherapy.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Biomarkers of Blood-Brain Barrier Disruption and Neuronal Injury | 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
| Measure | Time frame | Description |
|---|---|---|
| MRI Based Measures of Blood-Brain Barrier Integrity | 4 weeks after surgery | Assessment of blood-brain barrier disruption using contrast-enhanced 3-Tesla MRI, including quantitative and qualitative radiological measures of tumour enhancement and permeability. Imaging findings will be evaluated longitudinally and correlated with circulating biomarkers and clinical outcomes. |
| Immunohistochemical Characterisation of Blood-Brain Barrier Disruption | During surgical resection (single assessment) | Expression of blood-brain barrier-associated proteins within resected glioblastoma tissue assessed by immunohistochemical analysis. Findings will be used to characterize blood-brain barrier integrity and correlated with circulating biomarker and imaging measures. |
| Transcriptional Characterisation of Blood-Brain Barrier Disruption | During surgical resection (single assessment) | Gene expression profiling of resected glioblastoma tissue to identify transcriptional signatures associated with blood-brain barrier disruption and tumour biology. Results will be correlated with blood biomarker and imaging findings. |
| Neurocognitive Function Assessed by RBANS | Baseline (within 7 days before surgery), 4 weeks after surgery, and 4 weeks after completion of radiotherapy | Neurocognitive performance measured using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Changes in cognitive function will be examined in relation to blood-brain barrier integrity and treatment. |
Countries
Ireland
Contacts
CONTACTProfessor Donncha O'Brien, MB, BCh, BAO, MCh, FRCSI (SN)
Outcome results
None listed