Evaluating dietary intervention before surgical treatment for epilepsy
| ISRCTN | ISRCTN41638605 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN41638605 |
| ClinicalTrials.gov number | NCT02261753 |
| Secondary identifying numbers | 17696 |
- 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
Scientific
Department of Biostatistics
University of Liverpool
1st floor Duncan Building
Daulby Street
Liverpool
L69 3GA
United Kingdom
| c.papamichael@liverpool.ac.uk |
Study information
| Study design | Randomised; Interventional; Design type: Prevention |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Other |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient 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 | 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 study start date | 01/11/2014 |
| 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 | Both |
| Target number of participants | Planned Sample Size: 60; UK Sample Size: 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
- Austria
- Czech Republic
- England
- France
- Germany
- Italy
- Scotland
- Switzerland
- United Kingdom
- United States of America
Study participating centres
University of Liverpool
Liverpool
L69 3GA
United Kingdom
L69 3GA
United Kingdom
Krankenhaus Mara Maraweg
Bielefeld
33617
Germany
33617
Germany
Bristol Royal Hospital for Children
24 Upper Maudlin Street
Bristol
BS2 8BJ
United Kingdom
Bristol
BS2 8BJ
United Kingdom
Birmingham Children's Hospital
Steelhouse Lane
Birmingham
B4 6NH
United Kingdom
Birmingham
B4 6NH
United Kingdom
Royal Hospital for Sick Children
9 Sciennes Road
Edinburgh
EH9 1LF
United Kingdom
Edinburgh
EH9 1LF
United Kingdom
Children's Hospital Meyer
Viale Gaetano Pieraccini, 24
Florence
50139
Italy
Florence
50139
Italy
Hôpitaux Universitaires de Genève
Rue Gabrielle-Perret-Gentil 4
Geneva
1205
Switzerland
Geneva
1205
Switzerland
Great Ormond Street Hospital for Children
Great Ormond Street
London
WC1N 3JH
United Kingdom
London
WC1N 3JH
United Kingdom
HFME - Hospices Civils De Lyon
3 Quai des Célestins
Lyon
69002
France
Lyon
69002
France
Royal Manchester Children's Hospital
Oxford Road
Manchester
M13 9WL
United Kingdom
Manchester
M13 9WL
United Kingdom
Motol University Hospital
150 06, V Úvalu 84 Czechia
Prague
150 00
Czech Republic
Prague
150 00
Czech Republic
Ospedale Pediatrico Bambino Gesù
Piazza di Sant'Onofrio, 4
Rome
00165
Italy
Rome
00165
Italy
Hopital de Hautepierre
1 Avenue Molière
Strasbourg
67200
France
Strasbourg
67200
France
Schön Klinik Vogtareuth
Krankenhausstraße 20
Vogtareuth
83569
Germany
Vogtareuth
83569
Germany
Medical University Vienna
Spitalgasse 23
Vienna
1090
Austria
Vienna
1090
Austria
Johns Hopkins Hospital
1800 Orleans Street
Baltimore
21287
United States of America
Baltimore
21287
United States of America
Sponsor information
University College London (UK)
University/education
University/education
67 Riding House Street
London
W1P 7PN
England
United Kingdom
"ROR" |
https://ror.org/02jx3x895 |
|---|
Funders
Funder type
Government
Seventh Framework Programme
Government organisation / National government
Government organisation / National government
- Alternative name(s)
- EC Seventh Framework Programme, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, FP7
Results and Publications
| Intention to publish date | 26/07/2018 |
|---|---|
| Individual participant data (IPD) Intention to share | No |
| IPD sharing plan summary | Not provided at time of registration |
| 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 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 |
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.
