Exogenous Ketone Esters for Drug Resistant Epilepsy

NCT ID: NCT05670847

Last Updated: 2024-11-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-01-10

Study Completion Date

2025-07-01

Brief Summary

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

Detailed Description

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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.

Conditions

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Drug Resistant Epilepsy

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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 Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Study group

Children receiving exogenous ketone esters + standard of care

Group Type EXPERIMENTAL

Exogenous ketone ester

Intervention Type DRUG

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

Control group

Children receiving only standard of care

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Exogenous ketone ester

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

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

1 Year

Maximum Eligible Age

16 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Sohag University

OTHER

Sponsor Role lead

Responsible Party

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Elsayed Abdelkreem

Lecturer of Pediatrics

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Abdelrahim A Sadek, MD, PhD

Role: STUDY_CHAIR

Sohag University

Locations

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Department of Pediatrics at Sohag University Hospital

Sohag, , Egypt

Site Status RECRUITING

Countries

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Egypt

Central Contacts

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Elsayed M Abdelkreem, MD, PhD

Role: CONTACT

01114232126

Facility Contacts

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Abdelrahim A Sadek, MD, PhD

Role: primary

References

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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.

Reference Type BACKGROUND
PMID: 34510212 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22561291 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 29163194 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27475046 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11198492 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19889013 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 28276062 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25414234 (View on PubMed)

Other Identifiers

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Soh-Med-22-12-45

Identifier Type: -

Identifier Source: org_study_id