• Natasha E Schoeler, Louise Marston, Laura Lyons, Sally Halsall, Ruchika Jain, Siobhan Titre-Johnson, Maryam Balogun, Simon J R Heales, Simon Eaton, Michael Orford, Elizabeth Neal, Colin Reilly, Christin Eltze, Elma Stephen, Andrew A Mallick, Finbar O'Callaghan, Shakti Agrawal, Alasdair Parker, Martin Kirkpatrick, Andreas Brunklaus, Ailsa McLellan, Helen McCullagh, Rajib Samanta, Rachel Kneen, Hui Jeen Tan, Anita Devlin, Manish Prasad, Rohini Rattihalli, Helen Basu, Archana Desurkar, Ruth Williams, Penny Fallon, Irwin Nazareth, Nick Freemantle, J Helen Cross, and KIWE study group.
• Developmental Neurosciences Research and Teaching Department, University College London Great Ormond Street Institute of Child Health, London, UK; Dietetics, Great Ormond Street Hospital for Children, London, UK.
• Lancet Neurol. 2023 Dec 1; 22 (12): 111311241113-1124.

BackgroundMany infancy-onset epilepsies have poor prognosis for seizure control and neurodevelopmental outcome. Ketogenic diets can improve seizures in children older than 2 years and adults who are unresponsive to antiseizure medicines. We aimed to establish the efficacy of a classic ketogenic diet at reducing seizure frequency compared with further antiseizure medicine in infants with drug-resistant epilepsy.MethodsIn this phase 4, open-label, multicentre, randomised clinical trial, infants aged 1-24 months with drug-resistant epilepsy (defined as four or more seizures per week and two or more previous antiseizure medications) were recruited from 19 hospitals in the UK. Following a 1-week or 2-week observation period, participants were randomly assigned using a computer-generated schedule, without stratification, to either a classic ketogenic diet or a further antiseizure medication for 8 weeks. Treatment allocation was masked from research nurses involved in patient care, but not from participants. The primary outcome was the median number of seizures per day, recorded during weeks 6-8. All analyses were by modified intention to treat, which included all participants with available data. Participants were followed for up to 12 months. All serious adverse events were recorded. The trial is registered with the European Union Drug Regulating Authorities Clinical Trials Database (2013-002195-40). The trial was terminated early before all participants had reached 12 months of follow-up because of slow recruitment and end of funding.FindingsBetween Jan 1, 2015, and Sept 30, 2021, 155 infants were assessed for eligibility, of whom 136 met inclusion criteria and were randomly assigned; 75 (55%) were male and 61 (45%) were female. 78 infants were assigned to a ketogenic diet and 58 to antiseizure medication, of whom 61 and 47, respectively, had available data and were included in the modifified intention-to-treat analysis at week 8. The median number of seizures per day during weeks 6-8, accounting for baseline rate and randomised group, was similar between the ketogenic diet group (5 [IQR 1-16]) and antiseizure medication group (3 [IQR 2-11]; IRR 1·33, 95% CI 0·84-2·11). A similar number of infants with at least one serious adverse event was reported in both groups (40 [51%] of 78 participants in the ketogenic diet group and 26 [45%] of 58 participants in the antiseizure medication group). The most common serious adverse events were seizures in both groups. Three infants died during the trial, all of whom were randomly assigned a ketogenic diet: one child (who also had dystonic cerebral palsy) was found not breathing at home; one child died suddenly and unexpectedly at home; and one child went into cardiac arrest during routine surgery under anaesthetic. The deaths were judged unrelated to treatment by local principal investigators and confirmed by the data safety monitoring committee.InterpretationIn this phase 4 trial, a ketogenic diet did not differ in efficacy and tolerability to a further antiseizure medication, and it appears to be safe to use in infants with drug-resistant epilepsy. A ketogenic diet could be a treatment option in infants whose seizures continue despite previously trying two antiseizure medications.FundingNational Institute for Health and Care Research.Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.

17 keywords...

hide…