Efficacy of a Mixed Distancial Neuropsychological Rehabilitation Program in Patients With Grade 2 or 3 Diffuse Glioma

Official title

Efficacy of a Mixed Distancial Neuropsychological Rehabilitation Program in Patients With Grade 2 or 3 Diffuse Glioma : a Randomized Controlled Trial

Overview

Diffuse low-grade glioma are rare brain tumors affecting young subjects (median age at diagnosis 38 years for grade 2 and 49 years for grade 3). Cognitive symptoms are common in these patients, including memory, attention and executive function disorders. These disorders may have a deleterious impact on patients' professional, family and social lives, and have a negative impact on their quality of life. The benefits of cognitive rehabilitation have been demonstrated in other neurological pathologies. Furthermore, due to limited access to rehabilitation by neuropsychologists, some studies have evaluated the impact of digital cognitive rehabilitation programs. However, it cannot replace human support.

Detailed description

Diffuse Low-Grade Gliomas (DLGG) are rare tumors that affect young subjects (median age at diagnosis 38 years for grade 2 and 49 for grade 3). Overall survival varies from 5 to 15 years. Cognitive symptoms are common in these patients, notably impaired memory, attention and executive functions. For examples, in a prospective study conducted by our team, 40-53% of patients with grade 2 DLGG starting first-line chemotherapy had a cognitive complaint. These findings are in line with a recent meta-analysis based on 11 studies involving 313 glioma patients. These cognitive disorders can have a deleterious impact on patients' professional, family and social lives, and have a negative impact on their quality of life. The value of cognitive rehabilitation has been demonstrated in other neurological pathologies. Randomized controlled trials in DLGG are promising, but are ultimately few in number and/or have significant limitations (e.g. small number of patients, sample heterogeneity, questionable matching criteria, lack of control group). Furthermore, due to limited access to rehabilitation by neuropsychologists, some studies have evaluated the impact of digital cognitive rehabilitation programs. Although this type of tool seems particularly well suited to this young patient population, it cannot replace human accompaniment by a neuropsychologist. Indeed, we know the importance of the patient's human therapeutic alliance for adherence to a program. Moreover, certain psychopathological variables (e.g. anxiety, depression) have a significant impact on both neurocognitive abilities and complaints, justifying the intervention of a neuropsychologist specialized in oncology.

Interventions

• Other Cognitive Behavioral Therapy (CBT) neuropsychologist
  * CBT: at least 3 teleconsultations by the neuropsychologist (up to 1/week maximum) * Brain Head Quarters (BrainHQ) Digital program: 4 sessions of 40 minutes / week

Primary outcome measures

• Score in the Perceived Cognitive Impairment (PCI) subscale of Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) questionnaire [Time frame: 4 months]

Secondary outcome measures (12)

• Score in the PCI subscale of FACT-Cog questionnaire [Time frame: 6, 12 and 18 months]
• Score in the " Comments from the others " subscale of the FACT-Cog [Time frame: At baseline, 4, 6, 12 and 18 months]
• Score in the " Cognitive abilities perceived by the patient " subscale of the FACT-Cog [Time frame: At baseline, 4 months, 6 months, 12 months, 18 months]
• Score in the " Impact on quality of life " subscale of the FACT-Cog [Time frame: At baseline, 4 months, 6 months, 12 months, 18 months]
• FACT-Cog cognitive complaints questionnaire and the main neurocognitive domains [Time frame: At baseline, 4 months and 12 months]
• Score in the 2 scales of Prospective and Retrospective Memory Questionnaire (PRMQ) for patient and family caregiver [Time frame: At baseline, 4 months, 6 months, 12 months, 18 months]
• Difference in score on psychopathological distress via Hospital Anxiety and Depression Scale (HADS) [Time frame: At baseline, 4 months, 6 months, 12 months, 18 months]
• Difference in score on quality of life questionnaire Quality of Life Questionnaire - Core (30EORTC QLQ-C30) [Time frame: At baseline, 4 months, 6 months, 12 months, 18 months]
• Difference in score on quality of life questionnaire Quality of Life Questionnaire - Brain Neoplasm (EORTC QLQ-BN20) [Time frame: At baseline, 4 months, 6 months, 12 months, 18 months]
• Difference in score on fatigue via Multidimensional Fatigue Inventory (MFI-20) [Time frame: At baseline, 4 months, 6 months, 12 months, 18 months]
• Compliance of intervention [Time frame: 4 months]
• Difference in score on neurocognitive test via Montreal Cognitive Assessment (MoCA) [Time frame: At baseline and 4 and 12 months, respectively]

Eligibility criteria

Inclusion criteria

• Age ≥18 years old, no age limit;
• Histo-molecular diagnosis of grade 2 or 3 diffuse glioma according to World Health Organization (WHO) Classification 2016, regardless of oncological treatments previously received;
• Patient in satisfactory general condition for the study, defined by a WHO performance index ≤ 2 (ECOG-Performance Status (PS) ≤ 2);
• Neurosurgical excision (excluding biopsy) performed ≥ 12 months previously;
• In the case of oncological treatment, patient who has completed his sessions (radiotherapy, chemotherapy) for ≥ 6 months;
• Patient presenting a cognitive complaint defined as a response rated at least "Fairly" to at least one of the 2 items (n°20 and 25) assessing cognitive complaint in the EORTC QLQ-C30 questionnaire (i.e., defined as a score on the "Cognitive Functioning" scale ≤ 66.67);
• Fluent in French;
• Affiliation to the French Social Security System;
• Possible regular use of a digital tool with Internet access;
• Signature of informed consent prior to any study procedure.

Exclusion criteria

• Visual or auditory deficit not corrected to normal and/or preventing use of computer tools (i.e., homonymous lateral hemianopia is not a criterion for non-inclusion) ;
• Concurrent participation in a study with cognition as primary endpoint (e.g., "POLCA", " POLO " clinical trials) ;
• Legal incapacity or physical, psychological, social or geographical conditions preventing the patient from signing the consent form or completing the study ;
• Unstable or uncontrolled psychiatric syndrome (i.e., psychotropic treatments are not a criterion for non-inclusion if doses are stable) ;
• Known severe cognitive impairment (e.g., neurodegenerative disease, sequelae of head trauma, etc.) or defined by a score ≤ 20 on the MoCA test or impacting the ability to use digital tools at home ;
• Oncological treatment (radiotherapy and/or chemotherapy and/or surgery) planned within 4 months of inclusion. Targeted anti-Isocitrate DeHydrogenase (IDH) therapies are authorized.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Supportive care

Study locations

France · 8 centers

• Institut régional du Cancer de Montpellier — Montpellier
• CHU Amiens — Amiens
• CHU Bordeaux — Bordeaux
• CHU Lyon — Lyon
• Hôpital de la Timone — Marseille
• CHU Nancy — Nancy
• CHU Nîmes — Nîmes
• Institut Claudius Régaud — Toulouse

Publications

• Guerdoux E, Coutant L, Gourgou S, Mollevi C, Duc MS, Salasc F, Duffau H, Darlix A. Efficacy of hybrid remote neuropsychological rehabilitation on cognitive complaints in post-therapeutic lower-grade glioma: the FREEDOME randomized study protocol. Front Psychol. 2025 Sep 23;16:1650861. doi: 10.3389/fpsyg.2025.1650861. eCollection 2025. PMID 41064168

Identifiers

NCT: NCT06468176 · PROICM 2023-06 FRE

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗