Glutamate Excitotoxicity and Its Role in Glioblastoma Biology

Recruiting

• Conditions: Brain Tumor, Primary
• Interventions: Diagnostic Test: Blood, CSF and tumor samples

• Registration Number: NCT05775458
• Lead Sponsor: IRCCS San Raffaele

Brief Summary

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

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).

Study Timeline

• Study Start: 2020-06-01
• Study First Submitted: 2021-03-02
• Study First Submitted QC: 2023-03-16
• Study First Posted: 2023-03-20
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-22
• Last Update Posted: 2024-01-23
• Primary Completion: 2025-11-01
• Study Completion: 2026-09-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

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.

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Exclusion Criteria

• Age < 18 years
• Liver disease
• Severe anemia (Hb <8mg/dl)
• Pregnancy

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Adult neurosurgical patients	Blood, CSF and tumor samples	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).

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Characterization of Glutamate (Glu) levels in cerebrospinal fluid (CSF)	Baseline (before surgery)	CSF levels Glutamate (μM/L)
Characterization of Glutamate scavengers (Glu-sca) levels in cerebrospinal fluid (CSF)	Baseline (before surgery)	CSF levels GOT1 (UI/ml), GPT (UI/ml)

Trial Locations

Locations (1)

IRCCS San Raffaele Scientific Institute; 🇮🇹 Milan, Italy