Clinical trial NCT06770335: The FLaME Cognitive Rehabilitation Study for Childhood Brain Tumour
Official title: Strategy-based Cognitive Rehabilitation with Integrated Fatigue Management for Patients with Paediatric Brain Tumour (PBT): an Acceptability and Feasibility Study of the Fatigue, Learning and Memory Enrichment (FLaME) Intervention
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Childhood Brain Tumor
Childhood Brain Tumors
Pediatric Brain Neoplasms
Pediatric Brain Tumor
Keywords: Paediatric brain tumour
cognitive rehabilitation
cognition
fatigue
feasibility
acceptability
neuropsychology
neurocognitive
childhood brain tumour
Lead sponsor: Great Ormond Street Hospital for Children NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: NIHR Research for Patient Benefit (RfPB)
name: Success Charity
name: Child Brain Injury Trust
name: Cambridge University Hospitals NHS Foundation Trust
name: The UCL Great Ormond Street Institute of Child Health
name: Nottingham University Hospitals NHS Trust
First posted: 2025-01-13
Enrollment: 36
Sex: ALL
Minimum age (years): 7
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The feasibility study employs a randomised, parallel arm design with a standard care control group
Primary purpose: TREATMENT

Brief summary: Medical treatments have improved survival rates for children with brain tumours. However, most children experience long-term difficulties with 'cognition' (thinking skills such as memory and paying attention) and cognitive fatigue (excessive mental tiredness) after treatment. Thinking difficulties and fatigue can affect a child's ability to learn, and their social and emotional wellbeing. National guidance recommends treatment called 'cognitive rehabilitation' which teaches skills to improve or manage cognitive difficulties. Families often request this, but it is not usually available due to little research. Fatigue may also get in the way of children using and benefiting from cognitive rehabilitation. No research study has offered a fatigue treatment for children recovering from brain tumours. The study aims to see if it is practical and helpful to families to provide cognitive rehabilitation for children affected by brain tumours. The treatment focuses on strategies to help cognition. The investigators will see if adding strategies to manage fatigue helps. The study will include thirty-six 7-17-year-olds who have been treated for brain tumour at Great Ormond Street Hospital. All participants will have had an assessment describing cognitive strengths and weaknesses as part of usual care. Participants will be randomly allocated to one of three groups: 1) cognitive rehabilitation with fatigue management (12 weeks), 2) cognitive rehabilitation only (6 weeks), or 3) usual care. Each child and their carer will complete questionnaires before, during, and after the treatment, and an interview at the end of the treatment. This information will help the researchers see if families find the treatment helpful and practical to take part in, and if adding fatigue strategies is beneficial. Researchers will look at information such as the number of appointments attended, feedback about the treatment, and information about fatigue levels, cognition, and wellbeing. The findings will be used to develop a UK-wide study.

Detailed description: Treatment advances for childhood brain tumour in recent decades have substantially improved mortality rates but come at significant cost to the child's cognitive abilities, alongside the effects of the tumour itself. Up to 100% of children treated for a brain tumour experience some degree of cognitive difficulty despite most having achieved typical cognitive development prior to diagnosis. In most cases the child will experience multiple cognitive difficulties (e.g., with memory, attention, and speed of processing) that severely impact quality of life, mental health, access to education, academic and vocational attainment, and progress towards becoming an independent adult. These cognitive difficulties often emerge and become more severe over time (called 'late effects'). These difficulties have been frequently found in research studies and have informed a strong emphasis on the need for neurorehabilitation in national guidance for childhood brain tumour (e.g. NICE, 2005). Interventions aimed to address cognitive difficulties and support children to resume their developmental trajectory as closely as possible are clearly paramount. However, recent evidence finds that the recommendation for neurorehabilitation is rarely implemented, with cognitive rehabilitation almost entirely unavailable. Poor adherence to national guidance is compounded by the very limited research into cognitive rehabilitation interventions for children treated for brain tumour. The few interventions tried have also had poor feasibility of implementation (e.g., low completion rates) and low acceptability for patients and families.

Cognitive rehabilitation interventions typically involve either 1) 'massed drill-based' practice (sometimes called 'brain training') on cognitive training tasks where the individual repeats a cognitive training exercises over many sessions such as remembering an array of dots; 2) strategy-based approaches which teach strategies to optimise cognition (e.g., memory techniques such as mnemonics), and/or 3) external compensatory aids (e.g., visual reminders). There are few studies of cognitive rehabilitation for children with brain tumour, particularly good quality trials. A small number of studies have focused on drill-based rehabilitation, however, the feasibility and acceptability for this approach for children with brain tumour is low and has well documented problems in poor generalisation to skills beyond the repetitively trained task and poor maintenance of improvements. Rehabilitation in childhood brain injury has greatest potential when it includes cognitive strategy-use, is adapted for developmental level, involves systemic support, and empowers children to develop their own strategies. There is currently one good quality trial of a cognitive rehabilitation intervention that incorporates strategy-use for children with brain tumour. The intervention resulted in improvements in academic attainments and parental report of child attention skills, but with small effect sizes. The program also included a demanding drill-based practice component (requiring 50 hours in total), with only 60% of participants completing the intervention. A subsequent study omitted the drill-based practice and extended the strategy-use component, combining it with parent and teacher strategy support in a smaller pilot study. The power and generalisability of the findings are limited by a small sample size, however some improvements for cognition were found. Parents and children also rated high levels of satisfaction, particularly because the intervention improved their understanding of their cognitive strengths and weakness. Despite some promising findings for strategy-based cognitive rehabilitation, poor feasibility continues to be reflected in low completion rates. No cognitive rehabilitation intervention has addressed the high prevalence of cognitive fatigue (extreme mental tiredness) for children with brain tumours that could predictably limit engagement and completion of interventions. Despite strong recommendations a targeted intervention has yet to be developed for cognitive fatigue for children with brain tumours.

The research was designed to answer two key questions where there is a substantial evidence gap: 1) is a novel strategy-based cognitive rehabilitation intervention acceptable and feasible to children treated for brain tumour and their families, and 2) does adding fatigue management to the intervention improve feasibility and acceptability. The intervention is called The Fatigue, Learning and Memory Enrichment \[FLaME\] programme. The findings will tell us about the feasibility, acceptability, and preliminary outcomes of the FLaME programme. That is, it will tell us if there are any barriers to putting this intervention in place for young people with brain tumours, how acceptable they find it, and what the level of demand and satisfaction there is with the intervention. We will also seek preliminary information about intervention effectiveness to inform the optimum outcome measurement. This information will inform progress to a larger scale randomised controlled trial (RCT) to meet a substantial evidence gap in an under-researched group. There has been no cognitive rehabilitation trial for childhood brain tumour in the UK before, including within the National Health Service.

Eligibility criteria: Inclusion Criteria:

1. Age range: 7 years to 17 years, 11 months.
2. Received diagnosis and/or treatment/surveillance at GOSH for a childhood tumour that involved the CNS (brain) and/or oncology treatment to brain.
3. Received or receiving a neuropsychological assessment/consultation at GOSH over the course of the study period or in the 48 months prior to the study period, or under active surveillance with the neuro-oncology multidisciplinary team during the study period.
4. At least 6 months post-diagnosis/acute treatment (surgery and/or radiotherapy), and 3 months post-return to school, with stable disease.
5. One or more scores outside of normal limits (i.e. 1 SD above or below the mean in the direction indicating difficulty) in at least one neuropsychological domain (on performance-based tests or questionnaire-based rating scales).
6. Report impairment (z-score \> -0.67) in fatigue on one or more subscales of the PedsQL Multidimensional Fatigue Scale.
7. Capacity/competence of patient or parent/carer to provide informed

Exclusion Criteria:

1. Completed or having another targeted formal psychological intervention for cognitive rehabilitation or fatigue in the past 6 months.
2. Sensorimotor (e.g., visual-motor) impairment only on neuropsychological assessment without additional cognitive difficulty.
3. Current substance misuse from self-report.
4. Currently receiving formal psychiatric care for a diagnosed mental health disorder (including active suicidal ideation), excluding ADHD treatment (if a child has a diagnosis of ADHD they should be treated).
5. Intellectual Disability based on a standard score of more than 2 standard deviations below the mean on a general adaptive behaviour composite and, where available, the General Ability Index of intellect.
6. Patient and parent/carer is unable to communicate verbally and in written form in English.

Primary outcomes:
measure: Goal Based Outcome for management of fatigue
timeFrame: From enrolment to week 14
measure: Goal Based Outcome for management of cognitive difficulty
timeFrame: From enrolment to week 14
Secondary outcomes:
measure: Multidimensional Fatigue Scale
timeFrame: From enrolment to week 14
measure: Individual daily fatigue analogue scale
timeFrame: From enrolment to week 14
measure: % School attendance
timeFrame: From enrolment to week 14
measure: Behaviour Rating Inventory of Executive Function, Second Edition (BRIEF2)
timeFrame: From enrolment to week 14
measure: Paediatric Quality of Life Inventory (PedsQL) Core + Brain Tumour Module Cognitive Problems scale
timeFrame: From enrolment to week 14
measure: The Brief Illness Perceptions Questionnaire (BIPQ)
timeFrame: From enrolment to week 14
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Great Ormond Street Hospital for Children
Study officials:
affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Charlotte P Malcolm, DClinPsy
role: PRINCIPAL_INVESTIGATOR
affiliation: Great Ormond Street Hospital for Children NHS Foundation Trust
name: Faraneh Vargha-Khadem, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Treadgold B, Kennedy C, Spoudeas H, Sugden E, Walker D, Bull K. Paediatric neuro-oncology rehabilitation in the UK: carer and provider perspectives. BMJ Paediatr Open. 2019 Dec 15;3(1):e000567. doi: 10.1136/bmjpo-2019-000567. eCollection 2019.
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