Clinical Trial: Evaluating Dietary Intervention Before surgicaL Treatment for Epilepsy

Study Status: Not yet recruiting
Recruit Status: Not yet recruiting
Study Type: Interventional

Official Title: A Randomised Controlled Trial to Compare Seizure Remission Outcome Following Resective Surgery With or Without Prior Treatment With Ketogenic Diet in Children With Epilepsy the Result of Focal Cortica

Brief Summary: The investigators are undertaking the first European Randomised Controlled Trial (RCT) for epilepsy surgery in children with FCD type II, to prospectively evaluate the role of the KD prior to surgery in improving seizure outcome. The investigators will evaluate the role of KD as a disease-modifying treatment to achieve seizure control and improve neurodevelopment and quality of life. Children age 5 - 15 years with pharmacoresistant epilepsy believed to be the result of focal cortical dysplasia type II, considered to be surgically treatable, will be randomised to either receive 6m treatment presurgery with a ketogenic diet, or to proceed direct to surgery (no pretreatment). Primary outcome will be the time to achieve a period of 6 months of seizure freedom from the date of randomisation. Tissue resected at surgery will also be evaluated with regard to the degree of any methylation of DNA.

Detailed Summary:

Epilepsy surgery is now an accepted and effective management for individuals with drug resistant focal onset epilepsy in carefully selected candidates. This aside, only two RCTs have been performed in adults in temporal lobe epilepsy [1,2], and none in children . Malformations of cortical development are the most common pathology responsible for drug resistant focal epilepsy in childhood [3}. In retrospective studies, successful surgical resection resulting in seizure freedom in malformations of cortical development has been reported in 42-87% of cases [4], dependent on the series reviewed and the completeness of resection. Outcome is related to extent and completeness of resection, but the extent of tissue to be removed remains a challenge, especially in very young patients, where the limits of a lesion may be unclear and eloquent cortex may be involved.

FCD is one specific type of malformation, of localised areas of abnormal cortex that may be subdivided into I, II and III dependent on the pattern determined and cell types involved. This is by definition a histological diagnosis as was recently classified by the International League Against Epilepsy [5]. Specifically FCD type II can usually be suggested by characteristic changes on an MRI scan. These changes include increased cortical thickness, blurring of the cortical-white matter junction, increased signal on T2-weighted images, a radially oriented linear or conical transmantle strip of T2 hyperintensity, cortical thinning and localized brain atrophy. FCD type II may be subdivided histopathologically into IIa and IIb but it can be difficult to distinguish between the two radiologically.

The KD is a high fat diet with a proven efficacy in the treatment of drug resistant epilepsy in children [6]. An RCT performed in children aged 2-16 years diagnosed with drug resistant
Sponsor: University College, London

Current Primary Outcome: Time to 6 month remission [ Time Frame: Month 33 ]

the time to achieve a period of 6 months of seizure freedom from the date of randomisation pretreated KD group vs non pretreated group


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Time to first seizure from date of randomisation; [ Time Frame: 33 months ]
    The time to first seizure from date of randomisation, KD pretreated vs non pretreated group
  • Time to 12 month remission after randomisation [ Time Frame: 45 months ]
    Time to 12 month remission from seizures from date of randomisation, KD pretreated vs non pretreated group
  • Time to 24 month remission after randomisation [ Time Frame: 45 months ]
    Time to 24 months remission from seizures from date of randomisation, KD pretreated vs non pretreated group
  • Quality of life at 12 and at 24 months after randomisation; [ Time Frame: 45 months ]
    As determined by KINDL questionnaire, comparison of pretreated vs non pretreated group
  • Neuropsychological assessment at 12 and at 24 months after randomisation [ Time Frame: 45 months ]
    Comparison of neurodevelopmental change between pretreated and non pretreated KD group, as measured by Vineland adaptive behaviour scales
  • Methylation changes in tissue (DNA) from children pre-treated with the ketogenic diet compared to those not pretreated [ Time Frame: 60 months ]
    As measured from tissue resected at surgery
  • Proportion of immediate AEs following resective surgery (i.e. surgical complications within 30 days) [ Time Frame: 45 months ]
    As compared between groups, group pre-treated with KD compared to those without


Original Secondary Outcome:

  • Time to first seizure from date of randomisation; [ Time Frame: 33m ]
    The time to first seizure from date of randomisation, KD pretreated vs non pretreated group
  • Time to 12 month remission after randomisation [ Time Frame: 45m ]
    Time to 12m remission from seizures from date of randomisation, KD pretreated vs non pretreated group
  • Time to 24 month remission after randomisation [ Time Frame: 45m ]
    Time to 24m remission from seizures from date of randomisation, KD pretreated vs non pretreated group
  • Quality of life at 12 and at 24 months after randomisation; [ Time Frame: 45m ]
    As determined by KINDL questionnaire, comparison of pretreated vs non pretreated group
  • Neuropsychological assessment at 12 and at 24 months after randomisation [ Time Frame: 45m ]
    Comparison of neurodevelopmental change between pretreated and non pretreated KD group, as measured by Vineland adaptive behaviour scales
  • Methylation changes in tissue (DNA) from children pre-treated with the ketogenic diet compared to those not pretreated [ Time Frame: 60m ]
    As measured from tissue resected at surgery
  • Proportion of immediate AEs following resective surgery (i.e. surgical complications within 30 days) [ Time Frame: 45m ]
    As compared between groups, group pre-treated with KD compared to those without


Information By: University College, London

Dates:
Date Received: September 26, 2014
Date Started: October 2014
Date Completion: September 2018
Last Updated: October 13, 2014
Last Verified: October 2014