Condition category
Nervous System Diseases
Date applied
13/11/2014
Date assigned
13/11/2014
Last edited
19/09/2017
Prospective/Retrospective
Retrospectively registered
Overall trial status
Stopped
Recruitment status
Stopped

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

http://www.edible.org.uk/

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

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 measures

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

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

Sponsor information

Organisation

University College London (UK)

Sponsor details

67 Riding House Street
London
W1P 7PN
United Kingdom

Sponsor type

University/education

Website

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

Federal/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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes

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.