Exogenous Ketone Esters for Drug Resistant Epilepsy

Phase 2

Recruiting

• Conditions: Drug Resistant Epilepsy
• Interventions: Drug: Exogenous ketone ester

• Registration Number: NCT05670847
• Lead Sponsor: Sohag University

Brief Summary

This study aims to investigate the efficacy of add-on exogenous ketone esters for treating children with drug-resistant epilepsy

Detailed Description

Epilepsy is a common neurological disorder among children with significant neurobiological, cognitive, psychological, and social consequences. Seizures can usually be controlled by anti-seizure medications (ASMs) in up to two-thirds of children with epilepsy. However, this leaves a significant part of epileptic children whose seizures are not controlled by pharmacotherapy. Currently, available alternatives for drug-resistant epilepsy (DRE) include surgery, vagus nerve stimulation, and ketogenic diet (KD).

KD has been classically used for treating children with DRE. However, KD requires strict dietary restriction, which may not be applicable or acceptable for many patients, and is associated with several adverse effects, commonly including gastrointestinal (e.g., constipation, nausea, vomiting), cardiovascular (e.g., dyslipidemia), renal/genitourinary (e.g., renal calculi), and growth problems. Exogenous ketone esters (EKE) could be a more convenient and superior alternative to KD for children with DRE.

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: 2023-01-04
• 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: 60

Inclusion Criteria

• Drug-resistant epilepsy
• Seizure frequency ≥ 7 per week

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Exclusion Criteria

• Failure to obtain informed consent
• Recent intake of exogenous ketones, ketogenic diet, or any dietary restrictions/modifications
• Severe disease conditions, including hepatic, renal, respiratory, cardiac, gastrointestinal, endocrinal, and immune systems
• Hypo-/hyperglycemia
• Metabolic acidosis
• Ketosis (βHB > 2 mmol/L)
• GIT disorders, including gastritis/peptic ulcer, diarrhea/constipation, and irritable bowel disease
• Malnutrition/obesity
• Limitations to oral feeding (e.g., severe gastroesophageal reflux)
• Inborn errors of metabolism
• Chromosomal disorders
• Surgically-remediable epilepsy
• Allergies or any other contraindication to ketone supplements
• Inapplicable recording of seizures
• Incompliance to anti-seizure medications and/or irregular follow-up
• Recent 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
≥ 50% reduction in seizure frequency	From 28-days observation (baseline) phase to 28-days intervention phase	Proportion of patients achieving ≥ 50% reduction in seizure frequency

Secondary Outcome Measures

Name	Time	Method
Proportion of incompliance to exogenous ketone ester therapy	28-days intervention phase	Proportion of doses of exogenous ketone esters which were not administered by patients (as recorded by parents of included children)
Proportion of incompliance to anti-seizure medications (ASMs)	From 28-days observation (baseline) phase to 28-days intervention phase	Proportion of doses of anti-seizure medications (ASMs) which were not administered by children (as recorded by parents of included children)
Change in seizure severity assessed by National Hospital Seizure Severity Scale (NHS3)	From 28-days observation (baseline) phase to 28-days intervention phase	Change in seizure severity assessed by National Hospital Seizure Severity Scale (NHS3)
Change in cognitive domains	From 28-days observation (baseline) phase to 28-days intervention phase	Change in attention, alertness, and memmory, each rated by parents of included children at the end of 28-days intervention phase as no change, improvement, or regression in comparison with the preceding 28-days observation phase
Change in frequency of status epilepticus	From 28-days observation (baseline) phase to 28-days intervention phase	Change in the number of episodes of status epilepticus (evaluated from patient's medical records)
Change in seizure frequency	From 28-days observation (baseline) phase to 28-days intervention phase	Change in the number of seizures (as recorded by parents of included children)
Change in blood βHB	From baseline to 30 minutes, 1 hour, 2 hours, 4 hours, 2 days, 4 days, 7 days, 14 days, and 28 days study timepoints	Change in blood level of beta-hydroxybutyrate
Change in occurrence of possible adverse effects	From 28-days observation (baseline) phase to 28-days intervention phase	Change in occurrence of possible adverse effects
Change in blood glucose	From baseline to 30 minutes, 1 hour, 2 hours, 4 hours, 2 days, 4 days, 7 days, 14 days, and 28 days study timepoints	Change in blood level of glucose
Change in blood pH	From baseline to 30 minutes, 1 hour, 2 hours, 4 hours, 2 days, 4 days, 7 days, 14 days, and 28 days study timepoints	Change in blood level of pH
Change in EEG score	From baseline to 28 days study timepoint	Change in EEG score according to the scale developed by Walker \& Said (2014), which includes items related to encephalopathy, interictal epileptic discharge, and seizure presence

Trial Locations

Locations (1)

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