Ketogenic Diet in Infants With Epilepsy (KIWE) (KIWE)
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|ClinicalTrials.gov Identifier: NCT02205931|
Recruitment Status : Unknown
Verified May 2017 by University College, London.
Recruitment status was: Recruiting
First Posted : August 1, 2014
Last Update Posted : May 4, 2017
Epilepsy, a condition where individuals are prone to recurrent epileptic seizures, is the most common chronic neurological disorder in children. Epilepsy onset is most common in the first two years of life and is associated with poor prognosis for seizure control and neurodevelopmental outcome.
The ketogenic diet (KD) is a medically supervised diet that is high in fat and restricted in carbohydrates and protein. KD therapy has shown to be an effective treatment for seizures in children with epilepsy older than two. Associated benefits include: a reduced requirement for routine and emergency antiepileptic drugs (AED) and fewer seizure related hospital admissions. Although reports suggest that KD therapy improves seizures in younger children there is no high quality trial data that demonstrates effectiveness and safety in this age group. The KD is resource intensive, requiring dietetic and physician time; data is required to justify expansion of services to cater for the apparent need.
The investigators therefore propose a prospective multicentre randomised trial to investigate the effectiveness and safety of the KD in children with epilepsy under the age of 2, who have failed to respond to two or more AEDs. Children will be randomly assigned to either receive the KD or further AEDs. The allocated treatment will be started after a 2week baseline period, and it's effectiveness assessed after 8 weeks. Seizure diaries will be used to record seizures and related events, a questionnaire will be used to assess diet tolerance; also growth and blood biochemistry will be monitored.
The information obtained from this study is necessary to optimise choices in epilepsy treatment, aiming to improve outcomes and thus determine whether and when the KD should should be used.
|Condition or disease||Intervention/treatment||Phase|
|Epilepsy||Other: Ketogenic diet Drug: Antiepileptic drug therapy||Phase 4|
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The project proposed is a randomised controlled multicentre study of infants with epilepsy who have failed to respond to two or more pharmacological treatments (antiepileptic drugs (AEDs) or corticosteroids), comparing ketogenic diet to treatment with a further AED.
Children for this study will be recruited from 8 paediatric neurology centres in the South of England who have an established KD service for children with epilepsy. The collaborating paediatric neurologists based in these centres are named co-applicants on this proposal. All children ages 3 to 24 months will be considered if they have a diagnosis of epilepsy, namely continuing seizures despite a trial of 2 or more AEDs (including corticosteroids) and are experiencing at least 8 seizures a week.
Children will be excluded if they are shown to have: a metabolic disease contradicting the use of KD; a progressive neurological disease; severe gastrooesophageal reflux or have undergone a previous failed trial of KD. In addition, families should be able to attend clinic on the required timeline. KD meal plans will be accurately calculated for each child individually by a dietitian with consideration of daily calorie requirements, fat to carbohydrate ratio (3:1 or 4:1), adequate protein intake and vitamin and mineral supplementation. Ongoing adjustments to the diet by the dietitian are determined by weight gain and the degree of ketosis.
Baseline assessment: Written consent will be obtained from eligible children. Full history including seizure type, neurological examination, weight, length and head circumference will be documented. Randomisation to KD or standard AED group will be carried out with the support of the UCL PRIMENT Clinical Trials Unit (CTU).
Investigations to be performed in the KD group (or if clinically indicated in the AED group) will include FBC, U&Es, Glucose, LFTs, Calcium, Magnesium, Phosphate, Zinc, Selenium, Acylcarnitine profile, Cholesterol, Triglycerides, Urate, 25 hydroxy Vitamin D, urine calcium/creatinine, urine organic acids. An EEG will be performed if clinically indicated.
- Observation period of 2 weeks: No changes of regular AEDs. Emergency seizure treatments will continue as required( acute treatment with benzodiazepines). The following data will be recorded in a standardized diary (these data will continue to be recorded throughout the intervention period of 8 weeks): seizure types, seizure frequency, number of emergency seizure treatments required, contacts with the NHS due to seizure exacerbation (hospital admissions number of days, A&E and or GP attendances)
- Start of the classical KD or further AED. The classical KD will be administered as per protocol of the treating service. The recording of seizure types and frequency is to be continued.
- Second Assessment (4 weeks after the start of the treatment period, all patients): clinical review including weight; documentation of seizure frequency, and tolerability of the diet in randomised KD group by questionnaire.
- Third/final assessment (8 weeks after starting treatment/all patients). Clinical review including neurological examination, weight, length and head circumference. Documentation of seizure outcome (from seizure diaries). KD group only: completion of tolerability questionnaire, blood investigations (FBC, U&Es, Glucose, LFTs, plasma bicarbonate, calcium, magnesium, phosphate, zinc, selenium, acylcarnitine profile, cholesterol, triglycerides, urate, nonesterified fatty acids, blood ketones) and urine calcium/creatinine ratio. EEG will be performed if clinically indicated.
Dependent on seizure response, KD (diet group) or AED (standard AED group) will then be continued or changed. Those in the AED group of failed will be offered KD outside the context of the trial. It would be anticipated that clinical data would be collected on all patients to 12 months to determine retention rates.
Exit criteria: Children will withdraw from the treatment prior to 8 weeks should there be q >50% increase in seizure frequency from the baseline, or if intolerable side effects are not resolved by manipulation of KD or medication. A safety monitoring committee will be convened.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||160 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||A Randomised Controlled Trial of the Ketogenic Diet in the Treatment of Epilepsy in Children Under the Age of Two Years|
|Study Start Date :||January 2015|
|Estimated Primary Completion Date :||June 2018|
|Estimated Study Completion Date :||June 2019|
Experimental: Ketogenic diet
8 week trial of the ketogenic diet (KD) therapy. Children allocated to KD therapy will have their diets individually calculated by a paediatric dietitian with consideration of daily calorie requirements, adequate protein intake for growth and vitamin and mineral supplementation. All diets will be implemented according to a classical KD protocol, i.e. based on a ratio of fat to carbohydrate and protein that will usually be between 2:1 and 4:1.
Other: Ketogenic diet
The ketogenic diet is a high fat diet designed to mimic the effects on the body of starvation. The premise is the main energy intake is fat, which is utilised in the body and produces ketones.
Active Comparator: Antiepileptic drug therapy
The control intervention will be drug therapy with the most appropriate further antiepileptic drug (AED) for a particular child, depending on their presenting seizures and syndrome and previous drugs used, and chosen by the expert clinician responsible for management of the patient's epilepsy according to a standardised manual (consensus document) written following the initial workshop of the paediatric neurologists from all the trial centres.
Drug: Antiepileptic drug therapy
The control intervention will be drug therapy with the most appropriate further antiepileptic drug for a particular child, depending on their presenting seizures and syndrome and previous drugs used, and chosen by the expert clinician responsible for management of the patient's epilepsy.
- Number of seizures [ Time Frame: 6 - 8 weeks ]Number of seizures experienced during weeks 6 - 8
- Responder rate [ Time Frame: 8 weeks ]number of children seizure free and relationship between medium chain fatty acids and seizure control
- Retention on treatment [ Time Frame: 12 months ]retention on treatment, quality of life and neurodevelopmental outcome
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02205931
|Contact: Helen Cross, FRCP(UK)||0044 207 599 email@example.com|
|Contact: Siobhan Titre-Johnson, MScfirstname.lastname@example.org|
|Birmingham Children's Hospital||Recruiting|
|Birmingham, United Kingdom, B4 6NH|
|Contact: Shakti Agrawal, MBBS 0044 1213338149 email@example.com|
|Principal Investigator: Shakti Agrawal, MBBS|
|Bristol Royal Hospital for Children||Recruiting|
|Bristol, United Kingdom, BS2 8AE|
|Contact: Andrew Mallick, FRCPCH|
|Principal Investigator: Andrew Mallick|
|Cambridge, United Kingdom, CB2 0QQ|
|Contact: Alasdair Parker, MA 0044 1223 245151 firstname.lastname@example.org|
|Principal Investigator: Alasdair Parker, MA|
|Lancashire Teaching Hospitals NHS Foundation Trust||Recruiting|
|Lancashire, United Kingdom|
|Contact: Helen Basu Helen.Basu@lthtr.nhs.uk|
|Principal Investigator: Helen Basu|
|Leeds Teaching Hospital||Recruiting|
|Leeds, United Kingdom, LS1 3EX|
|Contact: Helen McCullagh, RCPCH 0044 113 243 2799 email@example.com|
|Principal Investigator: Helen McCullagh, RCPCH|
|Alder Hey Children's Hospital||Recruiting|
|Liverpool, United Kingdom, L12 2AP|
|Contact: Rachel Kneen, BMBS 0044 151 2525163 firstname.lastname@example.org|
|Principal Investigator: Rachel Kneen, BMBS|
|Great Ormond Street Hospital||Recruiting|
|London, United Kingdom, WC1N 3JH|
|Contact: Christin Eltze, MD Res 0044 207 405 9200 ext 5438 email@example.com|
|Principal Investigator: Christin Eltze, MD Res|
|St George's University Hospitals NHS Foundation Trust||Recruiting|
|London, United Kingdom|
|Contact: Penny Fallon Penny.Fallon@stgeorges.nhs.uk|
|Principal Investigator: Penny Fallon|
|Royal Manchester Children's Hospital||Recruiting|
|Manchester, United Kingdom, M13 0JE|
|Contact: Tim Martland, RCPCH 0044 161 276 1234 firstname.lastname@example.org|
|Principal Investigator: Tim Martland, RCPCH|
|The Newcastle Upon Tyne Hospitals NHS Foundation Trust||Recruiting|
|Newcastle upon Tyne, United Kingdom|
|Contact: Anita Devlin Anita.Devlin@nuth.nhs.uk|
|Principal Investigator: Anita Devlin|
|Sheffield Children's NHS Foundation Trust||Recruiting|
|Sheffield, United Kingdom|
|Contact: Archana Desurkar Archana.Desurkar@sch.nhs.uk|
|Principal Investigator: Archana Desurkar|
|Principal Investigator:||Helen Cross, FRCP(UK)||UCL Institute of Child Health|