Exogenous Ketone Esters for Refractory Status Epileptics

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

Detailed Description
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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.

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

Conditions
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Status Epilepticus

Intervention / Treatment
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* Drug: Exogenous ketone ester


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Refractory Generalized convulsive status epilepticus. Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 1 Year
Maximum Age: 10 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Eligible children will be randomized into two equal-sized groups. Study group: will receive exogenous ketone esters plus standard of care. Control group: will receive only standard of care.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study group<br>Children receiving exogenous ketone esters + standard of care | Drug: Exogenous ketone ester<br>* 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.<br>|
| No Intervention: Control group<br>Children receiving only standard of care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving electroclinical cessation of seizures | Proportions of patients who achieve cessation of BOTH clinical seizures (as observed clinically) AND electrical seizures (evaluated by electroencephalography [EEG]) | 60 minutes | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients achieving electroclinical cessation of seizures | Proportions of patients who achieve cessation of BOTH clinical seizures (as observed clinically) AND electrical seizures (evaluated by electroencephalography [EEG]) | 12 hours | 
| Time to electroclinical cessation of seizures | Time to cessation of BOTH clinical seizures (as observed clinically) AND electrical seizures (evaluated by electroencephalography [EEG]) | 24 hours | 
| Proportion of patients achieving electroclinical seizure freedom | Proportion of patients achieving freedom from BOTH clinical seizures (as observed clinically) AND electrical seizures (evaluated by electroencephalography [EEG]) | 24 hours | 
| Proportion of patients with super-refractory status epilepticus | Proportion of patients with persistent seizures for 24 hours or more after initiation of 3rd line medications (anesthetics) or recurrence of seizure during withdrawal of the anesthetics | 24 hours | 
| Proportion of patients with adverse gastrointestinal effects | Proportion of patients with adverse gastrointestinal effects (vomiting, diarrhea, abdominal pain) evaluated by direct observation and patient-reporting | 24 hours | 
| Change in blood beta-hydroxybutyrate level | Change in blood level of beta-hydroxybutyrate | From baseline to 30 minutes, 1 hour, 2 hours, 5 hours, 9 hours, and 12 hours study timepoints | 
| Change in blood glucose level | Change in blood level of glucose | From baseline to 30 minutes, 1 hour, 2 hours, 5 hours, 9 hours, and 12 hours study timepoints | 
| Change in blood pH | Change in blood pH | From baseline to 30 minutes, 1 hour, 2 hours, 5 hours, 9 hours, and 12 hours study timepoints | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Status epilepticus, Refractory status epilepticus, Generalized convulsive status epilepticus, Exogenous ketone esters, Children, Seizures