Evaluating dietary intervention before surgical treatment for epilepsy

ISRCTN	ISRCTN41638605
DOI	https://doi.org/10.1186/ISRCTN41638605
ClinicalTrials.gov (NCT)	NCT02261753
Protocol serial number	17696
Sponsor	University College London (UK)
Funder	Seventh Framework Programme

Submission date: 13/11/2014
Registration date: 13/11/2014
Last edited: 16/01/2020

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

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

Contact information

Dr Christiana Papamichael
Scientific

Department of Biostatistics
University of Liverpool
1st floor Duncan Building
Daulby Street
Liverpool
L69 3GA
United Kingdom

Email	c.papamichael@liverpool.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised; Interventional; Design type: Prevention
Secondary study design	Randomised controlled trial
Study type	Participant information sheet
Scientific title	Evaluating Dietary Intervention Before surgicaL treatment for Epilepsy (EDIBLE)
Study acronym	EDIBLE v1.0
Study objectives	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(s)	14/LO/1885
Health condition(s) or problem(s) studied	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
Primary outcome measure(s)	Time to 6 month remission; the time to 6 months of seizure freedom from the date of randomisation
Key secondary outcome measure(s)	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
Completion date	26/07/2017
Reason abandoned (if study stopped)	Participant recruitment issue

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	3 Years
Upper age limit	15 Years
Sex	All
Target sample size at registration	60
Key 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
Key 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
Date of first enrolment	01/11/2014
Date of final enrolment	26/07/2017

Locations

Countries of recruitment

United Kingdom
England
Scotland
Austria
Czech Republic
France
Germany
Italy
Switzerland
United States of America

Study participating centres

University of Liverpool

Liverpool
L69 3GA
United Kingdom

Krankenhaus Mara Maraweg

Bielefeld
33617
Germany

Bristol Royal Hospital for Children

24 Upper Maudlin Street
Bristol
BS2 8BJ
United Kingdom

Birmingham Children's Hospital

Steelhouse Lane
Birmingham
B4 6NH
United Kingdom

Royal Hospital for Sick Children

9 Sciennes Road
Edinburgh
EH9 1LF
United Kingdom

Children's Hospital Meyer

Viale Gaetano Pieraccini, 24
Florence
50139
Italy

Hôpitaux Universitaires de Genève

Rue Gabrielle-Perret-Gentil 4
Geneva
1205
Switzerland

Great Ormond Street Hospital for Children

Great Ormond Street
London
WC1N 3JH
United Kingdom

HFME - Hospices Civils De Lyon

3 Quai des Célestins
Lyon
69002
France

Royal Manchester Children's Hospital

Oxford Road
Manchester
M13 9WL
United Kingdom

Motol University Hospital

150 06, V Úvalu 84 Czechia
Prague
150 00
Czech Republic

Ospedale Pediatrico Bambino Gesù

Piazza di Sant'Onofrio, 4
Rome
00165
Italy

Hopital de Hautepierre

1 Avenue Molière
Strasbourg
67200
France

Schön Klinik Vogtareuth

Krankenhausstraße 20
Vogtareuth
83569
Germany

Medical University Vienna

Spitalgasse 23
Vienna
1090
Austria

Johns Hopkins Hospital

1800 Orleans Street
Baltimore
21287
United States of America

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan	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.

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
HRA research summary			28/06/2023	No	No
Participant information sheet	Participant information sheet	11/11/2025	11/11/2025	No	Yes
Study website	Study website	11/11/2025	11/11/2025	No	Yes

Editorial Notes

16/01/2020: ClinicalTrials.gov number added.
19/09/2017: Study has been stopped due to recruitment issues. Recruitment end date has been updated from 30/09/2019 to 26/07/2017. Overall trial end date has been updated from 30/09/2019 to 26/07/2017.
12/02/2016: Plain English summary added.