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Changing Agendas on Sleep, Treatment and Learning in Epilepsy (CASTLE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04610879
Recruitment Status : Terminated (Following the internal pilot, the study did not meet prespecified stop/go criteria for continuation.)
First Posted : November 2, 2020
Last Update Posted : November 2, 2020
Sponsor:
Collaborators:
King's College Hospital NHS Trust
University of Liverpool
Bangor University
Edge Hill University
Oxford Brookes University
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Rolandic Epilepsy Drug: Carbamazepine Drug: Levetiracetam Behavioral: Parent based sleep (PBS) intervention Phase 4

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 5 participants
Allocation: Randomized
Intervention Model: Factorial Assignment
Intervention Model 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. We have used a factorial trial design as this approach enables the efficient simultaneous investigation of anti-epileptic drug (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).
Masking: None (Open Label)
Primary Purpose: Health Services Research
Official Title: Randomised Factorial Design Controlled Trial Comparing Carbamazepine, Levetiracetam or Active Monitoring Combined With or Without Sleep Behaviour Intervention in Treatment Naive Children With Rolandic Epilepsy
Actual Study Start Date : August 2, 2019
Actual Primary Completion Date : September 23, 2020
Actual Study Completion Date : September 23, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Epilepsy

Arm Intervention/treatment
Active Comparator: Carbamazepine plus sleep intervention Drug: Carbamazepine
Treatment will be procured, prescribed and issued as per routine NHS practice. Generics can be prescribed.

Behavioral: Parent based sleep (PBS) intervention
The PBS intervention is an e-learning package for parents/primary carers and children with epilepsy. The PBS intervention offers parents education about normal sleep, advice about sleep-promoting practices and targeted strategies parents can employ to help their children to ''learn'' an appropriate set of sleep behaviours/habits and/or to unlearn inappropriate sleep behaviours.
Other Name: CASTLE Online Sleep Intervention (COSI)

Active Comparator: Carbamazepine plus standard care Drug: Carbamazepine
Treatment will be procured, prescribed and issued as per routine NHS practice. Generics can be prescribed.

Active Comparator: Levetiracetam plus sleep intervention Drug: Levetiracetam
Treatment will be procured, prescribed and issued as per routine NHS practice. Generics can be prescribed.

Behavioral: Parent based sleep (PBS) intervention
The PBS intervention is an e-learning package for parents/primary carers and children with epilepsy. The PBS intervention offers parents education about normal sleep, advice about sleep-promoting practices and targeted strategies parents can employ to help their children to ''learn'' an appropriate set of sleep behaviours/habits and/or to unlearn inappropriate sleep behaviours.
Other Name: CASTLE Online Sleep Intervention (COSI)

Active Comparator: Levetiracetam plus standard care Drug: Levetiracetam
Treatment will be procured, prescribed and issued as per routine NHS practice. Generics can be prescribed.

Active Comparator: No AED plus sleep intervention Behavioral: Parent based sleep (PBS) intervention
The PBS intervention is an e-learning package for parents/primary carers and children with epilepsy. The PBS intervention offers parents education about normal sleep, advice about sleep-promoting practices and targeted strategies parents can employ to help their children to ''learn'' an appropriate set of sleep behaviours/habits and/or to unlearn inappropriate sleep behaviours.
Other Name: CASTLE Online Sleep Intervention (COSI)

No Intervention: No AED plus standard care



Primary Outcome Measures :
  1. Time to 6-month seizure remission [ Time Frame: Up to 48 months ]
    To determine if carbamazepine or levetiracetam are superior to no anti-epileptic drugs

  2. Change from baseline to total sleep problem score as measured by the Children's Sleep Habits Questionnaire (CSHQ) [ Time Frame: At 3 months ]
    To determine if a Parent-Based Sleep intervention is superior to standard care


Secondary Outcome Measures :
  1. Total costs measured in Quality-Adjusted Life Years (QALYs) [ Time Frame: At 0, 3, 12, 24, 36 and 48 months ]
    To estimate the cost-utility of carbamazepine, levetiracetam and PBS

  2. 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 [ Time Frame: At 3, 6,12, 24, 36 and 48 months ]
    To compare time to treatment failure due to inadequate seizure control or unacceptable adverse reactions

  3. Time taken from randomisation to decision by child, parent or treating physician to be withdrawn from treatment due to inadequate seizure control [ Time Frame: At 3, 6,12, 24, 36 and 48 months ]
    To compare time to treatment failure due to inadequate seizure control

  4. Time taken from recruitment to decision by child, parent or treating physician to be withdrawn from trial due to unacceptable adverse reactions [ Time Frame: At 3, 6,12, 24, 36 and 48 months ]
    To compare time to treatment failure due to unacceptable adverse reactions

  5. Time to first seizure based on seizure report [ Time Frame: At 3, 6,12, 24, 36 and 48 months ]
    To compare time to first seizure

  6. Time to 12-month seizure remission based on seizure report [ Time Frame: At 3, 6,12, 24, 36 and 48 months ]
    To compare time to 12-month remission from seizures

  7. Total sleep problem score as measured by the Children's Sleep Habits Questionnaire (CSHQ) [ Time Frame: At 12, 24, 36 and 48 months ]
    To determine if a Parent-Based Sleep intervention is superior to standard care

  8. Total score in three chosen assessments delivered by the Cambridge Neuropsychological Test Automated Battery (CANTAB) [ Time Frame: At 0, 3, 6,12, 24, 36 and 48 months ]
    To compare measures of cognition across the different treatment groups

  9. Score change in Health Related Quality of Life in Children with Epilepsy - Child self-report scale (CHEQOL) [ Time Frame: At 0, 12, 24, 36 and 48 months ]
    To compare Health Related Quality of Life across the different treatment groups

  10. Total score on Strengths and Difficulties Questionnaire (SDQ) [ Time Frame: At 0, 12, 24, 36 and 48 months ]
    To compare measures of children's behaviour across the different treatment groups

  11. Records of adverse reactions [ Time Frame: At 3, 6, 12, 24, 36 and 48 months ]
    To identify any adverse reactions and their rate

  12. Score changes in Child Health Utility instrument (CHU9D) [ Time Frame: 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

  13. Score changes in EQ-5D-Y [ Time Frame: 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

  14. EQ-5D-5L score change [ Time Frame: 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

  15. Score changes in Parental Self-Efficacy Measure (PSAM) [ Time Frame: At 0, 3, 12, 24, 36 and 48 months ]
    To compare parenting self-efficacy across the different treatment groups

  16. Total sickness related school absences (days) [ Time Frame: At 0, 3, 6, 12, 24, 36 and 48 months ]
    To compare sickness related school absences across the different treatment groups

  17. Resource Use Questionnaire [ Time Frame: At 3, 12, 24, 36 and 48 months ]
    To determine the costs to the National Health Service (NHS)

  18. Hospital Episode Statistics (HES) Data [ Time Frame: 48 months, measured for the participant's study duration ]
    To determine the costs to the National Health Service (NHS)

  19. Patient Level Information and Costing System (PLICS) Data [ Time Frame: 48 months, measured for the participant's study duration ]
    To determine the costs to the National Health Service (NHS)


Other Outcome Measures:
  1. Summary of actigraphy variables (total sleep time/sleep latency/sleep efficiency) averaged over a 1-week period [ Time Frame: 1 week actigraphy (arranged centrally via Oxford unit) at baseline, 3 and 12 months ]
    To determine which sleep parameters change in primary carer and child dyads in different treatment groups



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   5 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Children diagnosed with RE (see International League Against Epilepsy Diagnostic Manual at https://www.epilepsydiagnosis.org/syndrome/ects-overview.html)
  2. EEG showing focal sharp waves with normal background (see International League Against Epilepsy Diagnostic Manual at https://www.epilepsydiagnosis.org/syndrome/ects-eeg.html)
  3. Aged ≥5 years and <13 years at the time of randomisation
  4. Currently untreated with antiepileptic drugs
  5. Written informed consent received from person with parental responsibility/legal representative.
  6. Family have an email address and regular internet access (for online sleep intervention)
  7. Parent and child are to have a good understanding of the English language

Exclusion Criteria:

  1. Known contraindication to any of the trial drugs
  2. Previously treated for epilepsy with antiepileptic drugs

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04610879


Locations
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United Kingdom
King's College Hospital NHS Foundation Trust
London, United Kingdom, SE5 8EF
Tameside Hospital
Manchester, United Kingdom
Whiston Hospital
Whiston, United Kingdom
Sponsors and Collaborators
King's College London
King's College Hospital NHS Trust
University of Liverpool
Bangor University
Edge Hill University
Oxford Brookes University
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Responsible Party: King's College London
ClinicalTrials.gov Identifier: NCT04610879    
Other Study ID Numbers: CASTLE
2018-003893-29 ( EudraCT Number )
RP-PG-0615-20007 ( Other Grant/Funding Number: NIHR )
First Posted: November 2, 2020    Key Record Dates
Last Update Posted: November 2, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: The current data sharing plans for this study are unknown and will be available at a later date

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Epilepsy
Epilepsy, Rolandic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Epilepsies, Partial
Epileptic Syndromes
Carbamazepine
Levetiracetam
Anticonvulsants
Nootropic Agents
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Psychotropic Drugs
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Sodium Channel Blockers
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers