MRS of Glioma Genomics

NCT05700071 | Recruiting

• 2 other identifiers: C21-272021-A03015-36
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

Brief Summary

In France, about 5000 new people with a primary malignant brain tumor are diagnosed each year. The most common primary tumors are gliomas, originating from glial cells (astrocytomas and oligodendrogliomas). Low-grade gliomas are mildly aggressive, but they often evolve into a more malignant form. Mutations in the genes encoding isocitrate dehydrogenase (IDH) are found in about 80% of low-grade gliomas and are associated with a favorable prognosis. Remarkably, IDH-mutated gliomas are characterized by a specific cellular metabolism causing the accumulation of D-2-hydroxyglutarate (2HG) in tumor cells. 2HG can be detected in vivo using 1H magnetic resonance spectroscopy (MRS) and is recognized as a unique, noninvasive biomarker of IDH-mutated gliomas. Noninvasive detection of IDH mutations via 2HG MRS represents a crucial step for decision-making and patient care. A subset of IDH-mutated tumors also presents a complete deletion of 1p and 19q chromosome arms (1p/19q codeletion). The 1p/19q codeletion is specifically linked to the oligodendroglial histologic subtype and it has been associated with a better patient outcome. However, the biological effects of this genetic alteration are still unclear and in vivo markers are lacking. Recently, we reported the first in vivo detection of the cystathionine molecule in human brain gliomas using MRS and explored the association between cystathionine accumulation and 1p/19q codeletion in gliomas. In this project, the investigation team will combine cutting edge MRI and MRS techniques for metabolic and microstructural characterization of brain tumors with the aim of providing novel reliable noninvasive biomarkers of tumor genetic subtypes. These methods will enable noninvasive identification of IDH-mutated gliomas and, potentially, 1p/19q codeleted gliomas. In addition, the researchers will investigate the utility of 2HG, cystathionine and MRI microstructural markers to monitor tumor response to anti-cancer treatments and tumor progression. The outputs of this project, altogether, may open new avenues to a better understanding of the pathophysiological mechanisms of oncogenesis and the design of new treatments for gliomas.

Conditions

Glioma

Keywords

Gliomas; Isocitrate dehydrogenase; 1p19q codeletion; MR Spectroscopy; MRI; Diagnosis; Treatment monitoring

Outcome Measures

Primary Outcomes (1)

• Metabolite concentrations by MRS

  Concentrations of 2-hydroxyglutarate and cystahionine measured by MRS will be correlated with IDH mutational status and 1p19q codeletion derived from ex vivo analyses in tumor tissue samples

  1.5 hour

Secondary Outcomes (3)

• Diffusion MRI metrics

  1,5 hours

• Metabolic changes during an anti-tumor treatment

  1 year

• Diffusion MRI and amide proton transfer signal changes during an anti-tumor treatment.

  1 year

Study Arms (1)

MRI examination

EXPERIMENTAL

Diagnostic Test: MRI

Interventions

MRI DIAGNOSTIC_TEST

MRI without contrast agent

MRI examination

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Affiliation à un régime de sécurité sociale (bénéficiaire ou ayant droit)
• Recueil du consentement écrit et éclairé
• Une des deux situations suivantes :
• Groupe 1 : Probable gliome de grade II/III, dont l'exérèse est programmée
• Groupe 2 : gliome de grade II ou III prouvé histologiquement avec statut IDH1/IDH2 connu, n'ayant reçu aucun autre traitement que la chirurgie, et devant débuter un traitement autre que la chirurgie.
• Présence d'un résidu tumoral évaluable (\>2 cm de diamètre en FLAIR)
• Index de Karnofsky \> 60
• Contraception efficace pendant la durée de la recherche, complété par un test de grossesse négatif pour les femmes en âge de procréer.

You may not qualify if:

• Contrindications à l'IRM:
• pace maker ou stimulateur neuronal, corps étranger métallique intraoculaire ou intracérébral, implant cochléaire, valve cardiaque ou matériel artériel chirurgical métallique non compatible IRM, matériel métallique susceptible de concentrer les impulsions de radio fréquence, claustrophobie
• femmes enceintes ou allaitantes
• Critères réglementaires :

Sponsors & Collaborators

• Institut National de la Santé Et de la Recherche Médicale, France: lead

Study Sites (2)

Pitié-Salpetrière Hospital

Paris, 75013, France

NOT YET RECRUITING

Hôpital Pitié Salpêtrière, 47 Boulevard de l'Hôpital, 75013 Paris

Paris, Île-de-France Region, 75013, France

RECRUITING

MeSH Terms

Conditions

Glioma; Disease

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Francesca Branzoli, PhD

  Paris Brain Institute, Paris, France

  STUDY DIRECTOR

• Marc Sanson, MD, PhD

  Paris Brain Institute, AP-HP, Paris, France

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Marc Sanson, MD, PhD

CONTACT

(0)1 42 16 03 91; marc.sanson@aphp.fr

Francesca Branzoli, PhD

CONTACT

(0)1 57 27 46 46; francesca.branzoli@icm-institute.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2023
• First Posted: January 26, 2023
• Study Start: March 6, 2023
• Primary Completion: March 3, 2026
• Study Completion (Estimated): March 2, 2028
• Last Updated: March 20, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

FR (2)