Title: Changing Agendas on Sleep, Treatment and Learning in Childhood Epilepsy (CASTLE)
Funder: Department of Health and Social Care

Abstract: Patient and Public Involvement We prepared this proposal with two parents (co-applicants), and organised a family consultation event. We have engaged three charities as PPI and dissemination partners. A children s and a parents advisory panel will advise on the research, and two members from each panel will join the Programme Management Group. Aims and Objectives This programme aims to improve outcomes for children with rolandic epilepsy by asking what impact different treatment policies have on their health and quality-of-life. (1) identifying a core set of outcome measures reflecting health and quality-of-life that are meaningful to families; (2) understanding and describing how concerns around drug treatment, learning and sleep problems influence decisions about management; (3) tailoring and evaluating an intervention to ameliorate sleep problems in childhood epilepsy; (4) evaluating the effectiveness and cost-effectiveness of drug-based seizure management and/or behavioural sleep interventions with regard to medical, learning, and patient-centred outcomes. Background and Rationale Epilepsy affects 1% of the population, mostly arises in childhood, and costs the NHS &pound;2 billion annually. Seizures are not the principal determinant of quality-of-life for children or parents, although seizures are the traditional focus of management. Older and newer antiepileptic drugs impair learning and the benefits over non-treatment are not fully established. Sleep disturbance is also a major comorbidity that may affect learning and quality of life. We will investigate the effectiveness of two different drugs versus no-treatment and/or parent-based sleep (PBS) interventions. We will study rolandic epilepsy (RE) as an exemplar because it is the most common type, the balance of drug benefit against side effects is at equipoise, nocturnal seizures are usual, sleep disturbance triggers seizures, and sleep problems are common. Research Plan This ambitious but achievable five year programme of integrated workpackages: WP1 (year 1-2) selects a core outcome set for evaluative research for children with RE, which will be used in WP4. WP2 (year 2-5) develops a qualitative evidence base to inform and support the choices and decisions that parents and their children with epilepsy make in relation to the management of RE. WP3 (year 1) tailors existing Parent-Based Sleep (PBS) interventions into an e-learning package (e-PBS) for children with epilepsy, and is deployed and evaluated in WP4. WP4 (year 2-5) is a factorial design pragmatic randomised trial comparing no-drug treatment vs (standard) carbamazepine vs (new) levetiracetam, with either e-PBS intervention or standard care. Dissemination and Projected Outputs In addition to scientific outputs, we will work with charities Epilepsy Action, Epilepsy Society and Cerebra, and relevant professional groups (Royal College of Paediatrics and Child Health, Epilepsy Specialist Nurses Association) to disseminate the key messages in plain language summaries to families, professional groups, managers, commissioners and policy-makers. We plan to deliver the most important outputs within a maximum of three to five years. We will deliver two outputs during the programme: (1) a new core outcome set for evaluative research in Year 2; and (2) a new online e-PBS intervention for children with epilepsy also in Year 2. Trial publications will follow soon after the programme, with specific policy recommendations for the NHS about (3) treatment vs no-treatment, (4) carbamazepine vs levetiracetam, and (5) sleep intervention in rolandic epilepsy within 3-5 years. Most of the output will be (6) generalizable to other common childhood epilepsies either immediately or within 5 years of the programme end. Relevant expertise and experience of the research team The team includes internationally respected clinicians and academics from paediatric neurology, sleep medicine and behavioural psychology, health services researchers, and two parents. All research applicants have experience of leading/participating in large-scale programmes of applied health research. The team has worked together for 18 months and many members have collaborated over the previous five years. Management and governance, including programme management and ethical implications An independent programme steering committee (PSC) will supervise the programme on behalf of NIHR and Sponsor. For WP4, there is an independent Trial Steering Committee (TSC), a Management Group for day-today affairs, and an Independent Data Safety Monitoring Committee led by Professor Helen Cross, chair of the NICE Guidelines Epilepsy panel. The programme includes children, an under-researched group requiring special ethical consideration. Justification of costs The programme will employ a half-time overall Programme Coordinator; 2 Family Engagement Officers; three junior researchers and a health economist part-time or fixed-term. The registered Liverpool CTRC will manage the clinical trial and has experience of epilepsy trials. Staff employed at the CTRC include a Trial Manager, two part-time statistical research associates, IT developer, data manager, trial coordinator assistant, Administrator, Quality Assurance Manager, Supervising Statistician, Supervising IS and Senior Data Manager. Large non-pay costs have been competitively tendered. PPI costs are guided by INVOLVE except where we have been specifically advised by our parent co-applicants. NHS support and research nurse costs were calculated through Kings College Hospital and approved by the South London CRN.

Lay abstract: Epilepsy is a common long-term condition of the brain that usually starts in childhood. Children with epilepsy experience seizures (fits). However, their learning, sleep, behaviour, self-esteem and mood are also often affected, and the condition can cause stress in the family. Treating epilepsy with drugs to reduce seizures has been the traditional goal of medical treatment. However, just reducing seizures doesn't necessarily make much difference to the way children and parents feel. The drugs used to treat epilepsy often slow down a patient s thinking and learning. Experts used to believe this was an acceptable price to pay to reduce seizures. However there is a common type of epilepsy where children grow out of their seizures in teenage years. We don t know if is better to treat these children with drugs or not, especially if this might have a negative effect on their learning. This is something that parents are also very concerned about. In order to address these uncertainties, we will work with children, parents, doctors and nurses to choose the best ways to measure health and quality of life for children with epilepsy. Then we will compare three groups of children: those on the standard drug treatment, those taking a newer drug that doesn't impact on thinking and learning as much, and those on no drug treatment. We will examine which is best to improve children s health and quality of life. Most children with epilepsy have sleep problems and wake in the night. Disturbed sleep in turn reduces learning ability and can also trigger seizures. Parents often get up to check on their child in case s/he is having a seizure, and sometimes sleep with the child because they are worried. This can make the parent very tired the next day, and affect their stress and concentration levels. We will adapt an existing sleep behavioural treatment to the sleep problems experienced by parents of children with epilepsy. Then we will test how well it works compared to standard treatment. The research will also include talking to parents and children about their experiences in relation to sleep, taking medication, learning and how taking part in the study has impacted on them. Two parents of children with epilepsy will advise on the study throughout its duration and a team of researchers will work with parents and children to learn about their experiences.

Research activity codes: 7.1 INDIVIDUAL CARE NEEDS;6.1 PHARMACEUTICALS
Health categories: NEUROLOGICAL