Exogenous Ketone Esters for Refractory Status Epileptics

Phase 2

Recruiting

• Conditions: Status Epilepticus
• Interventions: Drug: Exogenous ketone ester

• Registration Number: NCT05674552
• Lead Sponsor: Sohag University

Brief Summary

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

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2022-12-18
• Study First Submitted QC: 2022-12-31
• Study First Posted: 2023-01-06
• Study Start: 2023-01-10
• Status Verified: 2024-11
• Last Update Submitted: 2024-11-26
• Last Update Posted: 2024-11-27
• Primary Completion: 2025-06-30
• Study Completion: 2025-07-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Refractory Generalized convulsive status epilepticus.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Study group	Exogenous ketone ester	Children receiving exogenous ketone esters + standard of care

Primary Outcome Measures

Name	Time	Method
Proportion of patients achieving electroclinical cessation of seizures	60 minutes	Proportions of patients who achieve cessation of BOTH clinical seizures (as observed clinically) AND electrical seizures (evaluated by electroencephalography \[EEG\])

Secondary Outcome Measures

Name	Time	Method
Proportion of patients achieving electroclinical cessation of seizures	12 hours	Proportions of patients who achieve cessation of BOTH clinical seizures (as observed clinically) AND electrical seizures (evaluated by electroencephalography \[EEG\])
Time to electroclinical cessation of seizures	24 hours	Time to cessation of BOTH clinical seizures (as observed clinically) AND electrical seizures (evaluated by electroencephalography \[EEG\])
Proportion of patients achieving electroclinical seizure freedom	24 hours	Proportion of patients achieving freedom from BOTH clinical seizures (as observed clinically) AND electrical seizures (evaluated by electroencephalography \[EEG\])
Proportion of patients with super-refractory status epilepticus	24 hours	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
Proportion of patients with adverse gastrointestinal effects	24 hours	Proportion of patients with adverse gastrointestinal effects (vomiting, diarrhea, abdominal pain) evaluated by direct observation and patient-reporting
Change in blood beta-hydroxybutyrate level	From baseline to 30 minutes, 1 hour, 2 hours, 5 hours, 9 hours, and 12 hours study timepoints	Change in blood level of beta-hydroxybutyrate
Change in blood glucose level	From baseline to 30 minutes, 1 hour, 2 hours, 5 hours, 9 hours, and 12 hours study timepoints	Change in blood level of glucose
Change in blood pH	From baseline to 30 minutes, 1 hour, 2 hours, 5 hours, 9 hours, and 12 hours study timepoints	Change in blood pH

Trial Locations

Locations (1)

Department of Pediatrics at Sohag University Hospital; 🇪🇬 Sohag, Egypt