Glutamate Excitotoxicity and Its Role in Glioblastoma Biology

Study Overview
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Brief Summary
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Gliomas are the most frequent type of primary brain tumors in adults; among them glioblastoma multiforme (GBM) is the most malignant, being associated with the worst prognosis. Glutamate (Glu) is an aminoacid, responsible for essential functions in the Central Nervous System (CNS), acting both as metabolite and neurotransmitter. It is essential for regulating cellular metabolism and developmental synaptogenesis, cellular migration, differentiation and death. Recent scientific evidences have demonstrated alteration in Glu synthesis and signaling being directly involved in GBM growth and invasion

Detailed Description
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Glu and its scavenger's levels are measurable both in serum and in the cerebral-spinal fluid (CSF), thus making them ideal markers for tumor aggressiveness and disease activity as well as a potential target for new therapeutic approaches. Serum and CSF levels of glutamic oxaloacetic transaminase (GOT1), Glutamate Pyruvate Transaminase (GPT) and glutamate and aspartate levels of a total of 40 patients will be collected. Molecular biology analyses will be conducted and oncological and imaging data will be collected during follow-up in patients enrolled in the present studies. MRI imaging as well as blood sampling will be performed at definite timepoints (baseline and 3, 6 and 9 months follow-up).

Official Title
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Role of Glutamate-mediate Excitotoxicity in Invasion and Progression Processes of Glioblastoma Multiforme

Conditions
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Brain Tumor, Primary

Intervention / Treatment
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* Diagnostic Test: Blood, CSF and tumor samples


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients with a brain lesion suspected for GBM, candidate to gross total tumor resection (GTR), followed by radiotherapy and chemotherapy (concomitant and adjuvant). Patient able to provide informed consent. Exclusion Criteria: Age < 18 years Liver disease Severe anemia (Hb <8mg/dl) Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adult neurosurgical patients<br>Adult neurosurgical patients with a brain lesion suspected for GBM, candidate to gross total tumor resection (GTR), followed by radiotherapy and chemotherapy (concomitant and adjuvant). | Diagnostic Test: Blood, CSF and tumor samples<br>* Blood, CSF and brain tissue sampling of Glu and Glu regulatory proteins.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline characterization of Glutamate scavengers (Glu-sca) levels in serum | Serum GOT1 (UI/ml), GPT (UI/ml) | Baseline (before surgery) | 
| Baseline characterization of Glutamate (Glu) levels in serum | Serum Glutamate (μM/L) | Baseline (before surgery) | 
| Time changes in Glutamate scavengers (Glu-sca) levels in serum | Serum GOT1 (UI/ml), GPT (UI/ml) | At 3, 6, 9 months following surgery | 
| Time changes in Glutamate (Glu) levels in serum | Serum Glutamate (μM/L) | At 3, 6, 9 months following surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterization of Glutamate scavengers (Glu-sca) levels in cerebrospinal fluid (CSF) | CSF levels GOT1 (UI/ml), GPT (UI/ml) | Baseline (before surgery) | 
| Characterization of Glutamate (Glu) levels in cerebrospinal fluid (CSF) | CSF levels Glutamate (μM/L) | Baseline (before surgery) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Brain tumor, Glutamate