Drug Resistant Epilepsy
Conditions
Keywords
Drug resistant epilepsy, Exogenous ketone esters, Children
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.
Interventions
500 mg/kg orally three times daily (with at least 4 hours between each dose) for 28 days
Sponsors
Sohag University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
1 Years to 16 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ≥ 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 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 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 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 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in blood bicarbonate level | 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 bicarbonate |
| Change in serum sodium level | 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 serum sodium level |
| Change in serum potassium level | 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 serum potassium level |
| Change in hematological counts | From baseline to 28 days study timepoint | Change in hematological counts |
| Change in blood triglycerides level | From baseline to 28 days study timepoint | Change in blood triglycerides level |
| Change in blood free fatty acids level | From baseline to 28 days study timepoint | Change in blood free fatty acids level |
| Change in blood cholesterol level | From baseline to 28 days study timepoint | Change in blood cholesterol level |
| Change in HbA1c | From baseline to 28 days study timepoint | Change in hbA1c |
| Change in blood alanine transaminase level | From baseline to 28 days study timepoint | Change in blood level of alanine transaminase enzyme (ALT) |
| Change in serum creatinine level | From baseline to 28 days study timepoint | Change in serum level of creatinine |
| Change in blood lactate level | 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 lactate |
Countries
Egypt
Contacts
Primary ContactElsayed M Abdelkreem, MD, PhD
Outcome results
None listed