Exogenous Ketone Esters for Refractory Status Epileptics

NCT05674552 | Recruiting Phase 2

• 1 other identifier: Soh-Med-22-12-46
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to investigate the efficacy of add-on exogenous ketone esters for the treatment of children with refractory generalized convulsive status epilepticus

Conditions

Status Epilepticus

Keywords

Status epilepticus; Refractory status epilepticus; Generalized convulsive status epilepticus; Exogenous ketone esters; Children; Seizures

Outcome Measures

Primary Outcomes (1)

• Proportion of patients achieving electroclinical cessation of seizures

  Proportions of patients who achieve cessation of BOTH clinical seizures (as observed clinically) AND electrical seizures (evaluated by electroencephalography \[EEG\])

  60 minutes

Secondary Outcomes (8)

• Proportion of patients achieving electroclinical cessation of seizures

  12 hours

• Time to electroclinical cessation of seizures

  24 hours

• Proportion of patients achieving electroclinical seizure freedom

  24 hours

• Proportion of patients with super-refractory status epilepticus

  24 hours

• Proportion of patients with adverse gastrointestinal effects

  24 hours

Other Outcomes (11)

• Change in blood bicarbonates level

  From baseline to 30 minutes, 1 hour, 2 hours, 5 hours, 9 hours, and 12 hours study timepoints

• Change in blood lactate level

  From baseline to 30 minutes, 1 hour, 2 hours, 5 hours, 9 hours, and 12 hours study timepoints

• Change in hemoglobin level

  From baseline to 1 hour and 12 hours 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 over 5 min administered by nasogastric tube, followed after 1 hr by repeated hourly doses of 125 mg/kg for 8 hrs.

Study group

Eligibility Criteria

• Age: 1 Year - 10 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Refractory Generalized convulsive status epilepticus.

You may not qualify if:

• Failure to obtain informed consent.
• Recent intake of exogenous ketones, ketogenic diet, or any dietary restrictions/modifications.
• Hemodynamic or cardio-respiratory instability.
• Traumatic brain injury.
• Hypo-/hyperglycemia.
• Metabolic acidosis.
• Ketosis (βHB \> 2 mmol/L).
• Associated severe disease condition, including hepatic, renal, respiratory, cardiac, gastrointestinal, endocrinal, and immune systems.
• Malnutrition/obesity.
• Limitations to nasogastric tube feeding.
• Inborn errors of metabolism.
• Allergies or any other contraindication to exogenous ketone esters.
• Current or recent (within the last 24 hours) propofol therapy.
• Intake of carbonic-anhydrase inhibitors.

Sponsors & Collaborators

• Sohag University: lead

Study Sites (1)

Department of Pediatrics at Sohag University Hospital

Sohag, 82524, Egypt

RECRUITING

Related Publications (10)

• Arya R, Peariso K, Gainza-Lein M, Harvey J, Bergin A, Brenton JN, Burrows BT, Glauser T, Goodkin HP, Lai YC, Mikati MA, Fernandez IS, Tchapyjnikov D, Wilfong AA, Williams K, Loddenkemper T; pediatric Status Epilepticus Research Group (pSERG). Efficacy and safety of ketogenic diet for treatment of pediatric convulsive refractory status epilepticus. Epilepsy Res. 2018 Aug;144:1-6. doi: 10.1016/j.eplepsyres.2018.04.012. Epub 2018 Apr 27.

  PMID: 29727818 BACKGROUND

• Chomtho S, Uaariyapanichkul J, Chomtho K. Outcomes of parenteral vs enteral ketogenic diet in pediatric super-refractory status epilepticus. Seizure. 2022 Mar;96:79-85. doi: 10.1016/j.seizure.2022.01.019. Epub 2022 Feb 5.

  PMID: 35158320 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

• 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

• Schoeler NE, Simpson Z, Zhou R, Pujar S, Eltze C, Cross JH. Dietary Management of Children With Super-Refractory Status Epilepticus: A Systematic Review and Experience in a Single UK Tertiary Centre. Front Neurol. 2021 Mar 12;12:643105. doi: 10.3389/fneur.2021.643105. eCollection 2021.

  PMID: 33776895 BACKGROUND

• Si J, Wang Y, Xu J, Wang J. Antiepileptic effects of exogenous beta-hydroxybutyrate on kainic acid-induced epilepsy. Exp Ther Med. 2020 Dec;20(6):177. doi: 10.3892/etm.2020.9307. Epub 2020 Oct 9.

  PMID: 33101467 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

• 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

• 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

• Trinka E, Cock H, Hesdorffer D, Rossetti AO, Scheffer IE, Shinnar S, Shorvon S, Lowenstein DH. A definition and classification of status epilepticus--Report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015 Oct;56(10):1515-23. doi: 10.1111/epi.13121. Epub 2015 Sep 4.

  PMID: 26336950 BACKGROUND

MeSH Terms

Conditions

Status Epilepticus; Seizures

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

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 6, 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)