Changing Agendas on Sleep, Treatment and Learning in Epilepsy

NCT04610879 | Terminated Phase 4 DMC

• 3 other identifiers: CASTLE2018-003893-29RP-PG-0615-20007
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 3

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.

Conditions

Rolandic Epilepsy

Outcome Measures

Primary Outcomes (2)

• Time to 6-month seizure remission

  To determine if carbamazepine or levetiracetam are superior to no anti-epileptic drugs

  Up to 48 months

• Change from baseline to total sleep problem score as measured by the Children's Sleep Habits Questionnaire (CSHQ)

  To determine if a Parent-Based Sleep intervention is superior to standard care

  At 3 months

Secondary Outcomes (19)

• Total costs measured in Quality-Adjusted Life Years (QALYs)

  At 0, 3, 12, 24, 36 and 48 months

• 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

• 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

• 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

• Time to first seizure based on seizure report

  At 3, 6,12, 24, 36 and 48 months

Other Outcomes (1)

• Summary of actigraphy variables (total sleep time/sleep latency/sleep efficiency) averaged over a 1-week period

  1 week actigraphy (arranged centrally via Oxford unit) at baseline, 3 and 12 months

Study Arms (6)

Carbamazepine plus sleep intervention

ACTIVE COMPARATOR

Drug: Carbamazepine; Behavioral: Parent based sleep (PBS) intervention

Carbamazepine plus standard care

ACTIVE COMPARATOR

Drug: Carbamazepine

Levetiracetam plus sleep intervention

ACTIVE COMPARATOR

Drug: Levetiracetam; Behavioral: Parent based sleep (PBS) intervention

Levetiracetam plus standard care

ACTIVE COMPARATOR

Drug: Levetiracetam

No AED plus sleep intervention

ACTIVE COMPARATOR

Behavioral: Parent based sleep (PBS) intervention

No AED plus standard care

NO INTERVENTION

Interventions

Carbamazepine DRUG

Treatment will be procured, prescribed and issued as per routine NHS practice. Generics can be prescribed.

Carbamazepine plus sleep intervention; Carbamazepine plus standard care

Levetiracetam DRUG

Treatment will be procured, prescribed and issued as per routine NHS practice. Generics can be prescribed.

Levetiracetam plus sleep intervention; Levetiracetam plus standard care

Parent based sleep (PBS) intervention BEHAVIORAL

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.

Also known as: CASTLE Online Sleep Intervention (COSI)

Carbamazepine plus sleep intervention; Levetiracetam plus sleep intervention; No AED plus sleep intervention

Eligibility Criteria

• Age: 5 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• Known contraindication to any of the trial drugs
• Previously treated for epilepsy with antiepileptic drugs

Sponsors & Collaborators

• King's College London: lead
• King's College Hospital NHS Trust: collaborator
• University of Liverpool: collaborator
• Bangor University: collaborator
• Edge Hill University: collaborator
• Oxford Brookes University: collaborator

Study Sites (3)

King's College Hospital NHS Foundation Trust

London, SE5 8EF, United Kingdom

Location

Tameside Hospital

Manchester, United Kingdom

Location

Whiston Hospital

Whiston, United Kingdom

Location

MeSH Terms

Conditions

Epilepsy, Rolandic

Interventions

Carbamazepine; Levetiracetam; Methods

Condition Hierarchy (Ancestors)

Epilepsies, Partial; Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epileptic Syndromes

Intervention Hierarchy (Ancestors)

Dibenzazepines; Heterocyclic Compounds, 3-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Acetamides; Amides; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Investigative Techniques

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: July 9, 2019
• First Posted: November 2, 2020
• Study Start: August 2, 2019
• Primary Completion: September 23, 2020
• Study Completion: September 23, 2020
• Last Updated: November 2, 2020

Record last verified: 2020-10

Locations

GB (3)