Ketogenic diet treatment of epilepsy in infants
Research type
Research Study
Full title
A randomised controlled trial of the ketogenic diet in the treatment of epilepsy in children under the age of two years
IRAS ID
142888
Contact name
J Helen Cross
Contact email
Sponsor organisation
University College London
Eudract number
2013-002195-40
Research summary
Research Summary
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 seizurerelated 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 dietietic and physician time; data is required to justify expansion of services to cater for the apparent need.
We 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.
Summary of Results
Many babies with epilepsy continue to have seizures, despite use of standard anti-seizure medicines (ASMs). These babies are unlikely to make the same developmental progress as babies without epilepsy. Ketogenic diets (KD) are high in fat and low in carbohydrate and have been shown to reduce seizures in older children and adults who have failed ASMs. No good-quality studies have looked at how KD can help infants with epilepsy.
Babies (age 1-24 months) with epilepsy, who had tried at least two ASMs and continued to have at least four seizures per week, were allocated, at random, to start either the KD or another ASM. They then followed this treatment for 8 weeks. We wanted to know whether there was a difference in the number of seizures during weeks 6-8 compared to before they started this treatment. We also wanted to see how many babies became free of seizures, how many had at least 50% reduction in seizure frequency, how they tolerated the KD, whether they stayed on treatment, and whether they had made any developmental progress or had better quality of life after 12 months.
78 babies were allocated to start a KD and 58 to start another ASM. On average, the number of daily seizures was similar in both groups at 8 weeks, as was the chance of reducing the number of seizures by at least half, or becoming seizure-free. More babies in the ASM group changed the number or dose of other ASMs that they were already taking during the 8-week trial compared to babies in the KD group. Side effect score at 8 weeks was similar in both groups and the only differences in blood, urine or clinical examination results were as expected if you are following a KD. There was a suggestion that overall health may be improved further in the KD group at 8 weeks compared to the ASM group. Of 66 babies allocated to start a KD more than 12months before the study closed, 31 (47%) continued the diet to 12 months; of 47 allocated to start a further ASM, 21 (45%) continued to 12 months. Communication and socialisation improved more in the KD group compared to the ASM group at 12 months. There was no statistical difference between the two groups for all sections of the quality of life questionnaire at 12 months, except for ‘child’s temperament and mood’, and ‘child getting along with others’, which were better in the ASM group. A similar number of babies in both groups had at least one event (43% ASM; 51% KD), that caused them to go hospital or stay in hospital for longer. This was most commonly because of seizures. Three babies who started a KD died, but this was not felt to be related to the treatment.
The KD seems similar to further standard ASM in terms of how much it can reduce seizures and how well it is tolerated in babies aged under two years with drug-resistant epilepsy. Communication and socialisation may be further improved with a KD compared to ASM.REC name
London - Fulham Research Ethics Committee
REC reference
14/LO/1230
Date of REC Opinion
2 Sep 2014
REC opinion
Further Information Favourable Opinion