Changing Agendas on Sleep, Treatment and Learning in Epilepsy
- Conditions
- Rolandic Epilepsy
- Interventions
- Registration Number
- NCT04610879
- Lead Sponsor
- King's College London
- Brief Summary
Rolandic epilepsy (RE) is the most common type of epilepsy. Children with RE have seizures and can often find that their learning, sleep, behaviour, self-esteem and mood are affected.
As part of standard NHS care, children diagnosed with RE may be treated with standard anti-epileptic medicines, like carbamazepine, or no medicine at all. The medicines used to treat epilepsy often slow down a child's thinking and learning. In the past, doctors believed this was an acceptable price to pay to reduce seizures. However, with RE, where the seizures usually stop in teenage years, investigators do not know if it is better to treat these children with medicines or not, especially if the medicines might have a negative effect on their learning.
A newer medicine called levetiracetam has also been found to work in children with RE and has shown less problems with thinking and learning in adults. However, it is still no known if this is also the case for children and it has not been proven which of the three options (carbamazepine, levetiracetam or no treatment) would be best for RE patients. The CASTLE study aims to find this out.
In addition, it has been found that seizures often happen when a child has had poor sleep and they often come at night or early in the morning. It has been shown that sleep can be improved through practice without the need of medicines. There are established guidelines to help toddlers go to sleep, but nothing available that helps young people with epilepsy and their parents improve their sleep quality. In the CASTLE study, a sleep training plan has been developed for children with epilepsy and the trial aims to find out whether following this sleep training plan results in less seizures than using no sleep training at all.
- Detailed Description
The trial is a phase IV randomised factorial design controlled trial comparing carbamazepine, levetiracetam or active monitoring combined with or without sleep behaviour intervention. A factorial trial design has been used as this approach enables the efficient simultaneous investigation of AED (carbamazepine; levetiracetam; no AED) and sleep behaviour intervention (vs standard care) by including all participants in both analyses. In a factorial trial it is also possible to consider both the separate effects of each intervention and the benefits of receiving both interventions together (for example levetiracetam and sleep intervention).
The CASTLE trial will take place in NHS out-patient paediatric epilepsy and general paediatric clinics in the United Kingdom (UK).
Once consent has been obtained from the appropriate adult, and assent from the child if appropriate, by the delegated member of the research team the eligibility assessments will be completed, full eligibility confirmed (confirmation must be by a medically qualified doctor) and baseline data will be collected prior to randomisation.
Randomisation will be performed via a web based tool accessed by research team at site. This system is generated centrally by the Clinical Trial Research Centre (CTRC) using a computer algorithm concealed from the investigators and research teams/trial management group. In order to balance the groups, minimisation for variables believed to influence disease outcome and end points will be built into the randomisation algorithm.
Participants will be randomised to treatment with carbamazepine, levetiracetam or active monitoring. Where randomised to drug treatment, the randomised treatment should ideally begin on the day of randomisation or within 14 days of randomisation at the latest. Randomised treatment will continue for a minimum of 12 months and a maximum of 48 months. All treatments will be procured, prescribed and issued as per routine NHS practice.
Clinical data capture will be in the form of paper copies of Case Report Forms (CRFs) that will be returned as an on-going process from each centre to the CTRC. Patient/parent reported data will be collected directly on paper at each outpatient visit with the exception of CANTAB, which will be collected on iPads at the centre.
All trial documents (except raw Hospital Episode Statistics (HES) from NHS digital that will only be retained for 1 year) will be retained for 25 years from the End of Trial. The PI at each investigational centre must make arrangements to store the essential trial documents, (as defined in Essential Documents for the Conduct of a Clinical Trial (ICH E6, Guideline for Good Clinical Practice)) including the ISF, until the CTRC informs the investigator that the documents are no longer to be retained
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 5
- Children diagnosed with RE (see International League Against Epilepsy Diagnostic Manual at https://www.epilepsydiagnosis.org/syndrome/ects-overview.html)
- EEG showing focal sharp waves with normal background (see International League Against Epilepsy Diagnostic Manual at https://www.epilepsydiagnosis.org/syndrome/ects-eeg.html)
- Aged ≥5 years and <13 years at the time of randomisation
- Currently untreated with antiepileptic drugs
- Written informed consent received from person with parental responsibility/legal representative.
- Family have an email address and regular internet access (for online sleep intervention)
- Parent and child are to have a good understanding of the English language
- Known contraindication to any of the trial drugs
- Previously treated for epilepsy with antiepileptic drugs
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Carbamazepine plus sleep intervention Parent based sleep (PBS) intervention - Levetiracetam plus sleep intervention Levetiracetam - Levetiracetam plus sleep intervention Parent based sleep (PBS) intervention - No AED plus sleep intervention Parent based sleep (PBS) intervention - Carbamazepine plus sleep intervention Carbamazepine - Carbamazepine plus standard care Carbamazepine - Levetiracetam plus standard care Levetiracetam -
- Primary Outcome Measures
Name Time Method Time to 6-month seizure remission Up to 48 months To determine if carbamazepine or levetiracetam are superior to no anti-epileptic drugs
Change from baseline to total sleep problem score as measured by the Children's Sleep Habits Questionnaire (CSHQ) At 3 months To determine if a Parent-Based Sleep intervention is superior to standard care
- Secondary Outcome Measures
Name Time Method Time taken from randomisation to decision by child, parent or treating physician to be withdrawn from treatment due to inadequate seizure control or unacceptable adverse reactions At 3, 6,12, 24, 36 and 48 months To compare time to treatment failure due to inadequate seizure control or unacceptable adverse reactions
Time taken from randomisation to decision by child, parent or treating physician to be withdrawn from treatment due to inadequate seizure control At 3, 6,12, 24, 36 and 48 months To compare time to treatment failure due to inadequate seizure control
Time taken from recruitment to decision by child, parent or treating physician to be withdrawn from trial due to unacceptable adverse reactions At 3, 6,12, 24, 36 and 48 months To compare time to treatment failure due to unacceptable adverse reactions
Total costs measured in Quality-Adjusted Life Years (QALYs) At 0, 3, 12, 24, 36 and 48 months To estimate the cost-utility of carbamazepine, levetiracetam and PBS
EQ-5D-5L score change At 0, 3, 12, 24, 36 and 48 months To estimate health utilities and Quality-Adjusted Life Years (QALYs) across parents in the different treatment groups
Time to first seizure based on seizure report At 3, 6,12, 24, 36 and 48 months To compare time to first seizure
Time to 12-month seizure remission based on seizure report At 3, 6,12, 24, 36 and 48 months To compare time to 12-month remission from seizures
Total sleep problem score as measured by the Children's Sleep Habits Questionnaire (CSHQ) At 12, 24, 36 and 48 months To determine if a Parent-Based Sleep intervention is superior to standard care
Total score in three chosen assessments delivered by the Cambridge Neuropsychological Test Automated Battery (CANTAB) At 0, 3, 6,12, 24, 36 and 48 months To compare measures of cognition across the different treatment groups
Score change in Health Related Quality of Life in Children with Epilepsy - Child self-report scale (CHEQOL) At 0, 12, 24, 36 and 48 months To compare Health Related Quality of Life across the different treatment groups
Total score on Strengths and Difficulties Questionnaire (SDQ) At 0, 12, 24, 36 and 48 months To compare measures of children's behaviour across the different treatment groups
Records of adverse reactions At 3, 6, 12, 24, 36 and 48 months To identify any adverse reactions and their rate
Score changes in Child Health Utility instrument (CHU9D) At 0, 3, 12, 24, 36 and 48 months To estimate child health utilities and Quality-Adjusted Life Years (QALYs) across the different treatment groups
Score changes in EQ-5D-Y At 0, 3, 12, 24, 36 and 48 months To estimate child health utilities and Quality-Adjusted Life Years (QALYs) across the different treatment groups
Score changes in Parental Self-Efficacy Measure (PSAM) At 0, 3, 12, 24, 36 and 48 months To compare parenting self-efficacy across the different treatment groups
Resource Use Questionnaire At 3, 12, 24, 36 and 48 months To determine the costs to the National Health Service (NHS)
Hospital Episode Statistics (HES) Data 48 months, measured for the participant's study duration To determine the costs to the National Health Service (NHS)
Patient Level Information and Costing System (PLICS) Data 48 months, measured for the participant's study duration To determine the costs to the National Health Service (NHS)
Total sickness related school absences (days) At 0, 3, 6, 12, 24, 36 and 48 months To compare sickness related school absences across the different treatment groups
Trial Locations
- Locations (3)
King's College Hospital NHS Foundation Trust
🇬🇧London, United Kingdom
Whiston Hospital
🇬🇧Whiston, United Kingdom
Tameside Hospital
🇬🇧Manchester, United Kingdom