Clinical trial NCT05670847: Exogenous Ketone Esters for Drug Resistant Epilepsy
Official title: Efficacy of Ketone Esters for Children With Drug Resistant Epilepsy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Drug Resistant Epilepsy
Keywords: Drug resistant epilepsy
Exogenous ketone esters
Children
Lead sponsor: Sohag University
Sponsor class: OTHER
First posted: 2023-01-04
Enrollment: 60
Sex: ALL
Minimum age (years): 1
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

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

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

Primary outcomes:
measure: ≥ 50% reduction in seizure frequency
timeFrame: From 28-days observation (baseline) phase to 28-days intervention phase
Secondary outcomes:
measure: Proportion of incompliance to exogenous ketone ester therapy
timeFrame: 28-days intervention phase
measure: Proportion of incompliance to anti-seizure medications (ASMs)
timeFrame: From 28-days observation (baseline) phase to 28-days intervention phase
measure: Change in seizure severity assessed by National Hospital Seizure Severity Scale (NHS3)
timeFrame: From 28-days observation (baseline) phase to 28-days intervention phase
measure: Change in seizure frequency
timeFrame: From 28-days observation (baseline) phase to 28-days intervention phase
measure: Change in frequency of status epilepticus
timeFrame: From 28-days observation (baseline) phase to 28-days intervention phase
measure: Change in occurrence of possible adverse effects
timeFrame: From 28-days observation (baseline) phase to 28-days intervention phase
measure: Change in cognitive domains
timeFrame: From 28-days observation (baseline) phase to 28-days intervention phase
measure: Change in blood βHB
timeFrame: From baseline to 30 minutes, 1 hour, 2 hours, 4 hours, 2 days, 4 days, 7 days, 14 days, and 28 days study timepoints
measure: Change in blood glucose
timeFrame: From baseline to 30 minutes, 1 hour, 2 hours, 4 hours, 2 days, 4 days, 7 days, 14 days, and 28 days study timepoints
measure: Change in blood pH
timeFrame: From baseline to 30 minutes, 1 hour, 2 hours, 4 hours, 2 days, 4 days, 7 days, 14 days, and 28 days study timepoints
measure: Change in EEG score
timeFrame: From baseline to 28 days study timepoint
Other outcomes:
measure: Change in blood lactate level
timeFrame: From baseline to 30 minutes, 1 hour, 2 hours, 4 hours, 2 days, 4 days, 7 days, 14 days, and 28 days study timepoints
measure: Change in blood bicarbonate level
timeFrame: From baseline to 30 minutes, 1 hour, 2 hours, 4 hours, 2 days, 4 days, 7 days, 14 days, and 28 days study timepoints
measure: Change in serum sodium level
timeFrame: From baseline to 30 minutes, 1 hour, 2 hours, 4 hours, 2 days, 4 days, 7 days, 14 days, and 28 days study timepoints
measure: Change in serum potassium level
timeFrame: From baseline to 30 minutes, 1 hour, 2 hours, 4 hours, 2 days, 4 days, 7 days, 14 days, and 28 days study timepoints
measure: Change in hematological counts
timeFrame: From baseline to 28 days study timepoint
measure: Change in blood triglycerides level
timeFrame: From baseline to 28 days study timepoint
measure: Change in blood free fatty acids level
timeFrame: From baseline to 28 days study timepoint
measure: Change in blood cholesterol level
timeFrame: From baseline to 28 days study timepoint
measure: Change in HbA1c
timeFrame: From baseline to 28 days study timepoint
measure: Change in blood alanine transaminase level
timeFrame: From baseline to 28 days study timepoint
measure: Change in serum creatinine level
timeFrame: From baseline to 28 days study timepoint
Locations:
city: Sohag
country: Egypt
facility: Department of Pediatrics at Sohag University Hospital
Study officials:
affiliation: Sohag University
name: Abdelrahim A Sadek, MD, PhD
role: STUDY_CHAIR
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