Exogenous Ketone Esters for Refractory Status Epileptics

Официальное название

Efficacy of Exogenous Ketone Esters for Children With Refractory Convulsive Status Epileptics

Обзор

This study aims to investigate the efficacy of add-on exogenous ketone esters for the treatment of children with refractory generalized convulsive status epilepticus

Подробное описание

Generalized convulsive status epilepticus (GCSE) is a common neurological emergency in children with significant morbidity and mortality. Benzodiazepines (Bzs) are the initial anti-seizure medications (ASMs) for children with GCSE, but nearly a third of cases are not controlled by (Bzs). Moreover, about 40% of cases not responding to BZs are not controlled by second-line ASMs.

Ketogenic diet (KD) has been classically used for treating children with drug resistant epilepsy. Recently, KD has been used for refractory and super refractory status epilepticus. However, KD takes time to achieve ketosis and may be practically challenging in emergency situations and critically ill patients. Exogenous ketone esters (EKE) could be a more convenient and rapid way to achieve ketosis in acute settings.

Вмешательства

• Препарат Exogenous ketone ester
  500 mg/kg over 5 min administered by nasogastric tube, followed after 1 hr by repeated hourly doses of 125 mg/kg for 8 hrs.

Первичные конечные точки

• Proportion of patients achieving electroclinical cessation of seizures [Срок оценки: 60 minutes]

Вторичные конечные точки (8)

• Proportion of patients achieving electroclinical cessation of seizures [Срок оценки: 12 hours]
• Time to electroclinical cessation of seizures [Срок оценки: 24 hours]
• Proportion of patients achieving electroclinical seizure freedom [Срок оценки: 24 hours]
• Proportion of patients with super-refractory status epilepticus [Срок оценки: 24 hours]
• Proportion of patients with adverse gastrointestinal effects [Срок оценки: 24 hours]
• Change in blood beta-hydroxybutyrate level [Срок оценки: From baseline to 30 minutes, 1 hour, 2 hours, 5 hours, 9 hours, and 12 hours study timepoints]
• Change in blood glucose level [Срок оценки: From baseline to 30 minutes, 1 hour, 2 hours, 5 hours, 9 hours, and 12 hours study timepoints]
• Change in blood pH [Срок оценки: From baseline to 30 minutes, 1 hour, 2 hours, 5 hours, 9 hours, and 12 hours study timepoints]

Критерии участия

Критерии включения

• Refractory Generalized convulsive status epilepticus.

Критерии исключения

• Failure to obtain informed consent.
• Recent intake of exogenous ketones, ketogenic diet, or any dietary restrictions/modifications.
• Hemodynamic or cardio-respiratory instability.
• Traumatic brain injury.
• Hypo-/hyperglycemia.
• Metabolic acidosis.
• Ketosis (βHB > 2 mmol/L).
• Associated severe disease condition, including hepatic, renal, respiratory, cardiac, gastrointestinal, endocrinal, and immune systems.
• Malnutrition/obesity.
• Limitations to nasogastric tube feeding.
• Inborn errors of metabolism.
• Allergies or any other contraindication to exogenous ketone esters.
• Current or recent (within the last 24 hours) propofol therapy.
• Intake of carbonic-anhydrase inhibitors.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Египет · 1 центр

• Department of Pediatrics at Sohag University Hospital — Sohag

Публикации

• Arya R, Peariso K, Gainza-Lein M, Harvey J, Bergin A, Brenton JN, Burrows BT, Glauser T, Goodkin HP, Lai YC, Mikati MA, Fernandez IS, Tchapyjnikov D, Wilfong AA, Williams K, Loddenkemper T; pediatric Status Epilepticus Research Group (pSERG). Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus. Epilepsy Res. 2018 Aug;144:1-6. doi: 10.1016/j.epl PMID 29727818
• Chomtho S, Uaariyapanichkul J, Chomtho K. Outcomes of parenteral vs enteral ketogenic diet in pediatric super-refractory status epilepticus. Seizure. 2022 Mar;96:79-85. doi: 10.1016/j.seizure.2022.01.019. Epub 2022 Feb 5. PMID 35158320
• Clarke K, Tchabanenko K, Pawlosky R, Carter E, Todd King M, Musa-Veloso K, Ho M, Roberts A, Robertson J, Vanitallie TB, Veech RL. Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. Regul Toxicol Pharmacol. 2012 Aug;63(3):401-8. doi: 10.1016/j.yrtph.2012.04.008. Epub 2012 May 3. PMID 22561291
• Gilbert DL, Pyzik PL, Freeman JM. The ketogenic diet: seizure control correlates better with serum beta-hydroxybutyrate than with urine ketones. J Child Neurol. 2000 Dec;15(12):787-90. doi: 10.1177/088307380001501203. PMID 11198492
• Schoeler NE, Simpson Z, Zhou R, Pujar S, Eltze C, Cross JH. Dietary Management of Children With Super-Refractory Status Epilepticus: A Systematic Review and Experience in a Single UK Tertiary Centre. Front Neurol. 2021 Mar 12;12:643105. doi: 10.3389/fneur.2021.643105. eCollection 2021. PMID 33776895
• Si J, Wang Y, Xu J, Wang J. Antiepileptic effects of exogenous beta-hydroxybutyrate on kainic acid-induced epilepsy. Exp Ther Med. 2020 Dec;20(6):177. doi: 10.3892/etm.2020.9307. Epub 2020 Oct 9. PMID 33101467
• Stubbs BJ, Cox PJ, Evans RD, Santer P, Miller JJ, Faull OK, Magor-Elliott S, Hiyama S, Stirling M, Clarke K. On the Metabolism of Exogenous Ketones in Humans. Front Physiol. 2017 Oct 30;8:848. doi: 10.3389/fphys.2017.00848. eCollection 2017. PMID 29163194
• Carson RP, Herber DL, Pan Z, Phibbs F, Key AP, Gouelle A, Ergish P, Armour EA, Patel S, Duis J. Nutritional Formulation for Patients with Angelman Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study of Exogenous Ketones. J Nutr. 2021 Dec 3;151(12):3628-3636. doi: 10.1093/jn/nxab284. PMID 34510212

Идентификаторы

NCT: NCT05674552 · Soh-Med-22-12-46

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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