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NCT Number: NCT07731555

Characterization of the Blood-Brain Barrier in High-Grade Glioma Through Immunohistochemical, Transcriptional, Fluorescein and Radiological Analyses

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

Recruiting

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Beaumont RCSI Cancer Centre

Beaumont, D09, Ireland

Location status: Recruiting

Location contact

Aisling Hegarty, RGN, BSc, MSc, PhD

CONTACT

[email protected]

017977800

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Multimodal Blood Brain Barrier Assessment

Diagnostic Test

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.

Primary outcomes

  1. 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

  1. MRI Based Measures of Blood-Brain Barrier Integrity

    Time frame: 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.

  2. Immunohistochemical Characterisation of Blood-Brain Barrier Disruption

    Time frame: 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.

  3. Transcriptional Characterisation of Blood-Brain Barrier Disruption

    Time frame: 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.

  4. Neurocognitive Function Assessed by RBANS

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Professor Donncha O'Brien, MB, BCh, BAO, MCh, FRCSI (SN)

CONTACT

[email protected]

018093000

Sponsors and collaborators

Lead sponsor

Patrick Morris

Other

Registry information

Important dates

Study start
2022
Primary completion
2029
Study completion
2035
First posted
Jul 28, 2026
Registry last updated
Jul 28, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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