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

Glioma, Malignant Clinical Trial

— FREEDOME  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06468176
• Other study ID #: PROICM 2023-06 FRE
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 15, 2024
• Est. completion date: December 15, 2027

Study information

• Verified date: May 2024
• Source: Institut du Cancer de Montpellier - Val d'Aurelle
• Contact: Aurore MOUSSION
• Phone: 0467612446
• Email: Aurore.Moussion[@]icm.unicancer.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 187
• Est. completion date: December 15, 2027
• Est. primary completion date: October 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Glioma
• Glioma, Malignant

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Institut du Cancer de Montpellier - Val d'Aurelle

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Score in the Perceived Cognitive Impairment (PCI) subscale of Functional Assessment of Cancer Therapy - Cognitive Function (FACT-Cog) questionnaire	The FACT-Cog is a self-assessment questionnaire to estimate memory, attention, concentration, language, and thinking abilities of patients before, during, and after chemotherapy. This questionnaire, composed of 37 items consists of four subscales: cognitive impairments perceived by the patient (20 items), comments from others (4 items), cognitive abilities perceived by the patient (9items), and impact on quality of life (4 items). The Perceived Cognitive Impairments and the Comments from Others subscales are rated on 5-point Likert-type scale (from 0 = "Never" to 4 = "Several times a day"). An intensity 5-point Likert-type scale (from 0 "Not at all" to 4 "Very much") is used to rate perceived cognitive abilities and the impact on quality of life. For all subscales, a higher score represents better cognitive functioning or quality of life	4 months
Secondary	Score in the PCI subscale of FACT-Cog questionnaire	The FACT-Cog is a self-assessment questionnaire to estimate memory, attention, concentration, language, and thinking abilities of patients before, during, and after chemotherapy. This questionnaire, composed of 37 items consists of four subscales: cognitive impairments perceived by the patient (20 items), comments from others (4 items), cognitive abilities perceived by the patient (9items), and impact on quality of life (4 items). The Perceived Cognitive Impairments and the Comments from Others subscales are rated on 5-point Likert-type scale (from 0 = "Never" to 4 = "Several times a day"). An intensity 5-point Likert-type scale (from 0 "Not at all" to 4 "Very much") is used to rate perceived cognitive abilities and the impact on quality of life. For all subscales, a higher score represents better cognitive functioning or quality of life.	6, 12 and 18 months
Secondary	Score in the " Comments from the others " subscale of the FACT-Cog	The FACT-Cog is a self-assessment questionnaire to estimate memory, attention, concentration, language, and thinking abilities of patients before, during, and after chemotherapy. This questionnaire, composed of 37 items consists of four subscales including comments from other (4 items). This subscale is rated on 5-point Likert-type scale (from 0 = "Never" to 4 = "Several times a day"). A higher score represents better cognitive functioning or quality of life.	At baseline, 4, 6, 12 and 18 months
Secondary	Score in the " Cognitive abilities perceived by the patient " subscale of the FACT-Cog	The FACT-Cog is a self-assessment questionnaire to estimate memory, attention, concentration, language, and thinking abilities of patients before, during, and after chemotherapy. This questionnaire, composed of 37 items consists of four subscales including cognitive abilities perceived by the patient (9 items). An intensity 5-point Likert-type scale (from 0 "Not at all" to 4 "Very much") is used to rate perceived cognitive abilities. A higher score represents better cognitive functioning or quality of life.	At baseline, 4 months, 6 months, 12 months, 18 months
Secondary	Score in the " Impact on quality of life " subscale of the FACT-Cog	The FACT-Cog is a self-assessment questionnaire to estimate memory, attention, concentration, language, and thinking abilities of patients before, during, and after chemotherapy. This questionnaire, composed of 37 items consists of four subscales including impact on quality of life (4 items). An intensity 5-point Likert-type scale (from 0 "Not at all" to 4 "Very much") is used to rate the impact on quality of life. A higher score represents better cognitive functioning or quality of life.	At baseline, 4 months, 6 months, 12 months, 18 months
Secondary	FACT-Cog cognitive complaints questionnaire and the main neurocognitive domains	Correlations between scores on the 4 subscales of the FACT-Cog cognitive complaints questionnaire and the main neurocognitive domains (score on global functioning, executive functions, language, working memory, processing speed and social cognition).	At baseline, 4 months and 12 months
Secondary	Score in the 2 scales of Prospective and Retrospective Memory Questionnaire (PRMQ) for patient and family caregiver	The Prospective and Retrospective Memory Questionnaire (PRMQ) is one of the most commonly used scales to assess both retrospective memory (RM) and prospective memory (PM) complaints. The PRMQ is a 16-item, self-report measure of prospective and retrospective failures in everyday life. 8 items enquire about PM and 8 enquire about RM. The items were also designed to contain an equal number of items concerned with either self-cued memory or environmentally-cued memory, and with short-term versus long-term memory.	At baseline, 4 months, 6 months, 12 months, 18 months
Secondary	Difference in score on psychopathological distress via Hospital Anxiety and Depression Scale (HADS)	The HADS is a 14 items questionnaire: 7 items related to anxiety and 7 items related to depression scored on a scale. Scores for items in each subscale of the HADS are summed to produce an anxiety score (HADS-A) or a depression score (HADS-D), or can be added to produce a total score corresponding to emotional distress (HADS-T). Each item is rated on a 4-point Likert scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), for a total score ranging from 0-21 for each subscale. The entire scale (emotional distress) range from 0 to 42, with higher scores indicating more distress	At baseline, 4 months, 6 months, 12 months, 18 months
Secondary	Difference in score on quality of life questionnaire Quality of Life Questionnaire - Core (30EORTC QLQ-C30)	Developed by the EORTC, this self-reported questionnaire assesses the health-related quality of life of cancer patients in clinical trials. The questionnaire includes five functional scales (physical, everyday activity, cognitive, emotional, and social), three symptom scales (fatigue, pain, nausea and vomiting), a health/quality of life overall scale, and a number of additional elements assessing common symptoms (including dyspnea, loss of appetite, insomnia, constipation, and diarrhea), as well as, the perceived financial impact of the disease. All of the scales and single-item measures range in score from 0 to 100. A high scale score represents a higher response level.	At baseline, 4 months, 6 months, 12 months, 18 months
Secondary	Difference in score on quality of life questionnaire Quality of Life Questionnaire - Brain Neoplasm (EORTC QLQ-BN20)	This EORTC brain cancer specific questionnaire is intended to supplement the QLQ-C30. The QLQ-BN20 contains 20 items organized into four scales (three items each: future uncertainty, visual disorder, motor dysfunction, and communication deficit), and seven single items (headaches, seizures, drowsiness, hair loss, itchy skin, weakness of legs, and bladder control). All items are rated on a four-point Likert-type scale (1 = "not at all", 2 = "a little", 3 = "quite a bit", and 4 = "very much"), and are linearly transformed to a 0-100 scale, with higher scores indicating more severe symptoms.	At baseline, 4 months, 6 months, 12 months, 18 months
Secondary	Difference in score on fatigue via Multidimensional Fatigue Inventory (MFI-20)	The MFI-20 is a 20-item scale designed to evaluate five dimensions of fatigue: general fatigue, physical fatigue, reduced motivation, reduced activity, and mental fatigue. The patient positions himself on a 5-point scale, according to the fatigue he felt the days before the assessment. The " strongly agree " position is worth 5 points, and the " strongly disagree " position is worth 1 point. The score is calculated by adding up the points on the scale. The higher is the score, the more severe is the the fatigue.	At baseline, 4 months, 6 months, 12 months, 18 months
Secondary	Compliance of intervention	Patient adherence to the intervention defined as completion of at least 25 hours of the digital program out of the recommended 40 hours (calculated automatically by the software), and completion of the 3 neuropsycho-oncology (tele)consultations	4 months
Secondary	Difference in score on neurocognitive test via Montreal Cognitive Assessment (MoCA)	Lasting 10 to 15 minutes, the test assesses mild to moderate cognitive dysfunction, evaluating the following functions: attention, concentration, executive functions, memory, language, visuo-constructive abilities, abstraction skills, calculation, orientation.	At baseline and 4 and 12 months, respectively
Secondary	2 scores on the Prospective and Retrospective Memory Questionnaire (PRMQ) and the main cognitive domains	Correlations between the 2 scores on the PRMQ and the main cognitive domains (score for global functioning, executive functions, language, working memory, processing speed and social cognition)	At baseline, 4 months and 12 months
Secondary	Proportion of patients returning to work	Proportion of patients returning to work or increasing their working hours	At baseline, 4 months, 6 months, 12 months, 18 months
Secondary	Difference in score on depression via Beck Depression Inventory II (BDI-II)	The Beck Depression Inventory is used to detect depression and its severity. It is a self-assessment test with 21-items and 4 types of response. These range from 0 to 3 and describe the extent to which we identify the reality described. 0 means not identifying at all and 3 describes a fact which identify almost 100%. Four basic categories are established according to the results obtained : 0-13 = low depression, 14-19 = mild depression, 20-28 = moderate depression and 29-63 = severe depression.	At baseline, 4 months, 6 months, 12 months, 18 months
Secondary	Difference in score on anxiety via State-Trait Anxiety Inventory (STAI-Y)	The STAI-Y is a test designed to assess momentary and habitual anxiety. It comprises 2 scales of 20 items each: anxiety-state scale assesses the feelings of apprehension, tension, nervousness and concerns that the subject feels at the time of the consultation. It is an indicator of transient changes in anxiety caused by therapeutic or aversive situations.; The anxiety-trait scale assesses the feelings of apprehension, tension, nervousness and concerns that the subject usually experiences. The purpose of this scale is to identify anxiety as a stable disposition. It thus forms the starting point for therapeutic action.; The STAI-Y is also used to study the effect of anxiety on memory, learning performance or adjustment to stressful situations	At baseline, 4 months, 6 months, 12 months, 18 months
Secondary	Difference in score on irritability via Brief Irritability Test (BIT) for patient and family caregiver	The Brief Irritability Test is a brief, reliable, and valid self-report measure of irritability with 5-items. The answers are rated from never to always.	At baseline, 4 months, 6 months, 12 months, 18 months
Secondary	Difference in score on insomnia via Insomnia Severity Index (ISI)	The ISI is a 7-item self-report questionnaire assessing the nature, severity, and impact of insomnia. The usual recall period is the "last month" and the dimensions evaluated are: severity of sleep onset, sleep maintenance, and early morning awakening problems, sleep dissatisfaction, interference of sleep difficulties with daytime functioning, noticeability of sleep problems by others, and distress caused by the sleep difficulties. A 5-point Likert scale is used to rate each item (e.g., 0 = no problem; 4 = very severe problem), yielding a total score ranging from 0 to 28. The total score is interpreted as follows: absence of insomnia (0-7); sub-threshold insomnia (8-14); moderate insomnia (15-21); and severe insomnia (22-28).	At baseline, 4 months, 6 months, 12 months, 18 months
Secondary	Difference in score on cognitive abilities index via Wechsler Adult Intelligent Scale (WAIS-IV)	This test assesses cognitive abilities across various domains. It comprises 10 core subtests that yield four factor index scores (i.e., Verbal Comprehension: measures language use and long-term memory, Perceptual Reasoning: assesses logical reasoning and visual-spatial abilities, Working Memory: evaluates short-term memory, and Processing Speed: gauges processing speed) as well as the full-scale IQ. There are also five supplemental subtests that can be used as an alternative to the core subtests. In the FREEDOME study, the following sub-tests will be used: Digit Symbol Substitution Test; Code test; Verbal Digit-span test; Arithmetic	At Baseline, 4 months, 12 months
Secondary	Difference in score on verbal learning and memory via Hopkins Verbal Learning Test (HVLT)	This test provides a measure of verbal learning and memory. Following each administration, subjects were asked for an immediate free recall. Twenty minutes later, used for intercurrent tasks, subjects were asked for a delayed free recall, which was immediately followed by a recognition memory task. In this task, subjects listened to a list of 24 words, 12 belonging to the studied list and 12 were distractors; the subjects were asked to recognize the 12 studied words.	At Baseline, 4 months, 12 months
Secondary	Difference in score on processing speed and executive function via Stroop Delis-Kaplan test	The Delis-Kaplan Executive Function System (D-KEFS) Color-Word-Interference Test (CWIT; AKA Stroop test) is a widely used measure of processing speed and executive function. The Stroop test assesses the interference between color and word reading. Participants are presented with a list of color names (e.g., "red," "blue," "green") printed in incongruent colors (e.g., the word "red" printed in blue ink). The task requires individuals to name the color of the ink while inhibiting the automatic response to read the word itself. The interference effect occurs because our brains process the meaning of the word faster than the color information.	At Baseline, 4 months, 12 months
Secondary	Difference in score on verbal fluency via verbal fluency test	Two kinds of verbal fluency (VF) can be differentiated: phonemic fluency refers to the ability to name words with a given first letter (such as "S" or "P"), while in semantic VF words belonging to certain categories such as animals or fruits have to be enumerated. VF is an integral part of many neuropsychological test batteries	At Baseline, 4 months, 12 months
Secondary	Difference in score on visual attention via Trail Making Test (TMT)	The Trail Making Test is a neuropsychological test of visual attention and task switching. It comprises two parts in which the subject must connect a set of 25 points as quickly as possible while maintaining accuracy, i.e. avoiding making mistakes. The test provides information on visual search speed, visual exploration, information processing speed, mental flexibility and executive functioning.	At Baseline, 4 months, 12 months
Secondary	Difference in score on Theory of Mind via Reading the Mind in the Eyes Test (RMET)	The Reading the Mind in the Eyes Test (RMET) is a common measure of the Theory of Mind.; In the RMET, participants are presented with pictures of the eye regions of a face and required to select the word that best matches the model's complex mental state such as desire and goal.; It presents thirty-six photographs of the eye part of the face, each expressing complex mental states of the individuals pictured.	At Baseline, 4 months, 12 months