Plain English Summary
Background and study aims
Focal cortical dysplasia (FCD) is an abnormality of brain development that is a common cause of epilepsy, which results in repeated seizures. The ketogenic diet is a high fat, low carbohydrate, low protein diet designed to mimic the effects of fasting. The aim of this study is to find out whether the ketogenic diet improves seizure control, brain development and quality of life in children with FCD type II who are about to undergo surgery for epilepsy.
Who can participate?
Children aged 5 - 15 with epilepsy that is resistant to drug treatment and believed to be the result of FCD type II, who are considered to be surgically treatable.
What does the study involve?
Participants are randomly allocated to either receive 6 months of treatment with a ketogenic diet before their surgery, or to proceed directly to surgery (no pretreatment).
What are the possible benefits and risks of participating?
Not provided at time of registration
Where is the study run from?
University of Liverpool (UK)
When is the study starting and how long is it expected to run for?
November 2014 to September 2019
Who is funding the study?
EU Seventh Framework Programme
Who is the main contact?
Dr Christiana Papamichael
c.papamichael@liverpool.ac.uk
Trial website
Contact information
Type
Scientific
Primary contact
Dr Christiana Papamichael
ORCID ID
Contact details
Department of Biostatistics
University of Liverpool
1st floor Duncan Building
Daulby Street
Liverpool
L69 3GA
United Kingdom
-
c.papamichael@liverpool.ac.uk
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT02261753
Protocol/serial number
17696
Study information
Scientific title
Evaluating Dietary Intervention Before surgicaL treatment for Epilepsy (EDIBLE)
Acronym
EDIBLE v1.0
Study hypothesis
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 the ketogenic diet as a disease-modifying treatment to achieve seizure control and improve neurodevelopment and quality of life. The ketogenic diet is a high fat, low carbohydrate, low protein diet designed to mimic the effects of fasting on the body. It will be administered by calculation as per local standardised classical ketogenic diet protocol with utilisation of long chain fat in a ratio of 2:1 to 4:1 carbohydrate and protein.
Ethics approval
14/LO/1885
Study design
Randomised; Interventional; Design type: Prevention
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Children; Subtopic: All Diagnoses; Disease: All Diseases
Intervention
Children will be randomised to either receive 6m treatment presurgery with a ketogenic diet, or to proceed direct to surgery (no pretreatment).
Intervention type
Other
Phase
Not Applicable
Drug names
Primary outcome measure
Time to 6 month remission; the time to 6 months of seizure freedom from the date of randomisation
Secondary outcome measures
Current as of 19/09/2017:
1. Time to first seizure from date of randomisation;
2. Time to 12 month remission after randomisation;
3. Time to 24 month remission after randomisation (if enough time for follow-up is available);
4. Quality of life at 12 months after randomisation (and at 24 months if enough time for follow-up is available);
5. Adaptive behaviour assessment at 12 months (() after randomisation (and at 24 months if enough time for follow-up is available);
6. Methylation changes in tissue (DNA) from children pre-treated with the ketogenic diet. Tissue will be stored in the EEBB, and further distributed to DESIRE partners (Baker IDI Heart and Diabetes Institute Holdings Ltd, Varionostic GMBH,CEGAT) for further analysis;
7. Changes in peripheral DNA (blood platelets) following treatment with the KD. Tissue will be stored in the EEBB, and further distributed to DESIRE partners (Baker IDI Heart and Diabetes Institute Holdings Ltd, Varionostic GMBH,CEGAT) for further analysis;
8. Proportion of immediate AEs following resective surgery (i.e. surgical complications within 30 days) in the group pre-treated with KD compared to those without.
9. Compare the general AE occurrence between the group pre-treated with KD compared to the group without KD pre-treatment.
Previous secondary outcome meaures:
1. Methylation changes in tissue (DNA); Timepoint(s): At the time of surgery between ketogenic diet pre-treatment group vs non pre-treated group
2. Neuropsychological assessment; Timepoint(s): Neuropsychological assessment at 12 and at 24 months after randomisation
3. Peripheral DNA changes (blood); Timepoint(s): At baseline and at the time of surgery
4. Proportion of immediate AEs following resective surgery; Timepoint(s): Surgical complications within 30 days from surgery
5. Quality of life; Timepoint(s): Quality of life at 12 and at 24 months after randomisation
Overall trial start date
01/11/2014
Overall trial end date
26/07/2017
Reason abandoned (if study stopped)
Participant recruitment issue
Eligibility
Participant inclusion criteria
Current as of 19/09/2017:
This is applicable to all participating countries with trial approvals working to Protocol V5.0 06/09/2016 except Austria and Germany (working to Protocol V2.0 17/03/2015)
1. Children aged 3 - 15 years;
2. MRI changes consistent with a diagnosis of FCD type II a or b;
3. History of at least two epileptic seizures in the past 6 months before randomisation;
4. Seizure semiology consistent with focal onset, agreed after pre-surgical discussion to be surgically treatable;
5. Parent/ legal representative willing to give consent.
Previous inclusion criteria:
1. Children aged 5-15 years
2. MRI changes consistent with a diagnosis of Focal Cortical Dysplasia type II a or b
3. History of continuing seizures for less than 5 years
4. History of at least two epileptic seizures in the past 6 months before randomisation
5. Seizure semiology consistent with focal onset, agreed after pre-surgical discussion to be surgically treatable
6. Failure of at least two antiepileptic drugs to control the seizures
7. Parent/legal representative willing to give consent
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
Planned Sample Size: 60; UK Sample Size: 60
Participant exclusion criteria
1. Previous use of the ketogenic diet
2. Not a surgical candidate for Focal Cortical Dysplasia resection
3. Administration of the ketogenic diet is medically contraindicated
Recruitment start date
01/11/2014
Recruitment end date
26/07/2017
Locations
Countries of recruitment
Austria, Czech Republic, France, Germany, Italy, Switzerland, United Kingdom, United States of America
Trial participating centre
University of Liverpool
Liverpool
L69 3GA
United Kingdom
Trial participating centre
Krankenhaus Mara Maraweg
Bielefeld,
33617
Germany
Trial participating centre
Bristol Royal Hospital for Children
24 Upper Maudlin Street
Bristol
BS2 8BJ
United Kingdom
Trial participating centre
Birmingham Children's Hospital
Steelhouse Lane
Birmingham
B4 6NH
United Kingdom
Trial participating centre
Royal Hospital for Sick Children
9 Sciennes Road
Edinburgh
EH9 1LF
United Kingdom
Trial participating centre
Children's Hospital Meyer
Viale Gaetano Pieraccini, 24
Florence
50139
Italy
Trial participating centre
Hôpitaux Universitaires de Genève
Rue Gabrielle-Perret-Gentil 4
Geneva
1205
Switzerland
Trial participating centre
Great Ormond Street Hospital for Children
Great Ormond Street
London
WC1N 3JH
United Kingdom
Trial participating centre
HFME - Hospices Civils De Lyon
3 Quai des Célestins
Lyon
69002
France
Trial participating centre
Royal Manchester Children's Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom
Trial participating centre
Motol University Hospital
150 06, V Úvalu 84 Czechia
Prague
150 00
Czech Republic
Trial participating centre
Ospedale Pediatrico Bambino Gesù
Piazza di Sant'Onofrio, 4
Rome
00165
Italy
Trial participating centre
Hopital de Hautepierre
1 Avenue Molière
Strasbourg
67200
France
Trial participating centre
Schön Klinik Vogtareuth
Krankenhausstraße 20
Vogtareuth
83569
Germany
Trial participating centre
Medical University Vienna
Spitalgasse 23
Vienna
1090
Austria
Trial participating centre
Johns Hopkins Hospital
1800 Orleans Street
Baltimore
21287,
United States of America
Funders
Funder type
Government
Funder name
Seventh Framework Programme
Alternative name(s)
EC Seventh Framework Programme, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, FP7
Funding Body Type
government organisation
Funding Body Subtype
National government
Location
Results and Publications
Publication and dissemination plan
The results from all the children will be analysed together and published as soon as possible in a peered reviewed scientific journal irrespective of findings. Participants and their parents or legal representative will be able to have collective findings disseminated to them in plain English by their neurologist or paediatrician. A lay summary will be made available on the trial website. Results will also be disseminated through conference presentations.
IPD sharing statement:
No individual data will be analysed. The identity of participants will remain confidential and results from blood and tissues samples donated for research purposes will not be copied into participants' medical notes.
Intention to publish date
26/07/2018
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list