Clinical trial NCT05775458: Glutamate Excitotoxicity and Its Role in Glioblastoma Biology
Official title: Role of Glutamate-mediate Excitotoxicity in Invasion and Progression Processes of Glioblastoma Multiforme
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Brain Tumor, Primary
Keywords: Brain tumor
Glutamate
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
First posted: 2023-03-20
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult patients with a brain lesion suspected for GBM, candidate to gross total tumor resection (GTR), followed by radiotherapy and chemotherapy (concomitant and adjuvant).

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).

Eligibility criteria: 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

Primary outcomes:
measure: Baseline characterization of Glutamate scavengers (Glu-sca) levels in serum
timeFrame: Baseline (before surgery)
measure: Baseline characterization of Glutamate (Glu) levels in serum
timeFrame: Baseline (before surgery)
measure: Time changes in Glutamate scavengers (Glu-sca) levels in serum
timeFrame: At 3, 6, 9 months following surgery
measure: Time changes in Glutamate (Glu) levels in serum
timeFrame: At 3, 6, 9 months following surgery
Secondary outcomes:
measure: Characterization of Glutamate scavengers (Glu-sca) levels in cerebrospinal fluid (CSF)
timeFrame: Baseline (before surgery)
measure: Characterization of Glutamate (Glu) levels in cerebrospinal fluid (CSF)
timeFrame: Baseline (before surgery)
Other outcomes:
measure: Association between Glutamate metabolism and Glioblastoma molecular signature
timeFrame: Baseline levels of markers
Locations:
city: Milan
country: Italy
facility: IRCCS San Raffaele Scientific Institute
Study officials:
affiliation: IRCCS San Raffaele
name: Pietro Mortini, MD, Prof.
role: STUDY_DIRECTOR
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