Exogenous Ketone Esters for Drug Resistant Epilepsy

NCT05670847 | Recruiting Phase 2

• 1 other identifier: Soh-Med-22-12-45
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Drug Resistant Epilepsy

Keywords

Drug resistant epilepsy; Exogenous ketone esters; Children

Outcome Measures

Primary Outcomes (1)

• ≥ 50% reduction in seizure frequency

  Proportion of patients achieving ≥ 50% reduction in seizure frequency

  From 28-days observation (baseline) phase to 28-days intervention phase

Secondary Outcomes (11)

• Proportion of incompliance to exogenous ketone ester therapy

  28-days intervention phase

• Proportion of incompliance to anti-seizure medications (ASMs)

  From 28-days observation (baseline) phase to 28-days intervention phase

• 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 frequency

  From 28-days observation (baseline) phase to 28-days intervention phase

• Change in frequency of status epilepticus

  From 28-days observation (baseline) phase to 28-days intervention phase

Other Outcomes (11)

• 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 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 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

Study Arms (2)

Study group

EXPERIMENTAL

Children receiving exogenous ketone esters + standard of care

Drug: Exogenous ketone ester

Control group

NO INTERVENTION

Children receiving only standard of care

Interventions

Exogenous ketone ester DRUG

500 mg/kg orally three times daily (with at least 4 hours between each dose) for 28 days

Study group

Eligibility Criteria

• Age: 1 Year - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sohag University: lead

Study Sites (1)

Department of Pediatrics at Sohag University Hospital

Sohag, 82524, Egypt

RECRUITING

Related Publications (8)

• Carson RP, Herber DL, Pan Z, Phibbs F, Key AP, Gouelle A, Ergish P, Armour EA, Patel S, Duis J. Nutritional Formulation for Patients with Angelman Syndrome: A Randomized, Double-Blind, Placebo-Controlled Study of Exogenous Ketones. J Nutr. 2021 Dec 3;151(12):3628-3636. doi: 10.1093/jn/nxab284.

  PMID: 34510212 BACKGROUND

• Clarke K, Tchabanenko K, Pawlosky R, Carter E, Todd King M, Musa-Veloso K, Ho M, Roberts A, Robertson J, Vanitallie TB, Veech RL. Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. Regul Toxicol Pharmacol. 2012 Aug;63(3):401-8. doi: 10.1016/j.yrtph.2012.04.008. Epub 2012 May 3.

  PMID: 22561291 BACKGROUND

• Stubbs BJ, Cox PJ, Evans RD, Santer P, Miller JJ, Faull OK, Magor-Elliott S, Hiyama S, Stirling M, Clarke K. On the Metabolism of Exogenous Ketones in Humans. Front Physiol. 2017 Oct 30;8:848. doi: 10.3389/fphys.2017.00848. eCollection 2017.

  PMID: 29163194 BACKGROUND

• Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab. 2016 Aug 9;24(2):256-68. doi: 10.1016/j.cmet.2016.07.010. Epub 2016 Jul 27.

  PMID: 27475046 BACKGROUND

• Gilbert DL, Pyzik PL, Freeman JM. The ketogenic diet: seizure control correlates better with serum beta-hydroxybutyrate than with urine ketones. J Child Neurol. 2000 Dec;15(12):787-90. doi: 10.1177/088307380001501203.

  PMID: 11198492 BACKGROUND

• Kwan P, Arzimanoglou A, Berg AT, Brodie MJ, Allen Hauser W, Mathern G, Moshe SL, Perucca E, Wiebe S, French J. Definition of drug resistant epilepsy: consensus proposal by the ad hoc Task Force of the ILAE Commission on Therapeutic Strategies. Epilepsia. 2010 Jun;51(6):1069-77. doi: 10.1111/j.1528-1167.2009.02397.x. Epub 2009 Nov 3.

  PMID: 19889013 BACKGROUND

• Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, Hirsch E, Jain S, Mathern GW, Moshe SL, Nordli DR, Perucca E, Tomson T, Wiebe S, Zhang YH, Zuberi SM. ILAE classification of the epilepsies: Position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017 Apr;58(4):512-521. doi: 10.1111/epi.13709. Epub 2017 Mar 8.

  PMID: 28276062 BACKGROUND

• Walker I, Said RR. Predictors of Ketogenic Diet Efficacy in Children Based on the Electroencephalogram (EEG). J Child Neurol. 2015 Sep;30(10):1270-4. doi: 10.1177/0883073814556888. Epub 2014 Nov 20.

  PMID: 25414234 BACKGROUND

MeSH Terms

Conditions

Drug Resistant Epilepsy

Condition Hierarchy (Ancestors)

Epilepsy; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Abdelrahim A Sadek, MD, PhD

  Sohag University

  STUDY CHAIR

Central Study Contacts

Elsayed M Abdelkreem, MD, PhD

CONTACT

01114232126; d.elsayedmohammed@med.sohag.edu.eg

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Pediatrics

Model Details: 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.

Study Record Dates

• First Submitted: December 18, 2022
• First Posted: January 4, 2023
• Study Start: January 10, 2023
• Primary Completion: June 30, 2025
• Study Completion: July 1, 2025
• Last Updated: November 27, 2024

Record last verified: 2024-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Unidentified individual participant data (IPD) underlying study results will be available upon reasonable request 6-months after publication

Locations

EG (1)