KD Treatment for Super-refractory Status Epilepticus

NCT07496749 | Recruiting

• 1 other identifier: KS2025230-001
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 14

Brief Summary

The purpose of the study is to investigate to evaluate the efficacy and safety of ketogenic diet (KD) as an adjunctive therapy in patients with Super Refractory Status Epilepticus (SRSE) in the intensive care unit (ICU).

Conditions

Super-refractory Status Epilepticus

Keywords

ketogenic diet; status epilepticus; refractory status epilepticus; encephalitis; intensive care unit

Outcome Measures

Primary Outcomes (1)

• Time to cessation of SRSE

  Calculation Method: Based on electroencephalogram (EEG) and clinical seizure activity, the therapeutic efficacy is categorized into three levels: Grade I (Seizure-free): Electrographic and clinical status epilepticus is completely controlled, and follow-up EEG shows resolution of electrographic status epilepticus; record the number of days required to achieve this. Grade II (Partially effective): Epileptiform discharges are reduced by more than 50%; record the number of days required to achieve this. Grade III (Ineffective): Epileptiform discharges are reduced by less than 50%; the recorded number of days required is 14 days.

  2 weeks

Study Arms (2)

standard medical therapy for SRSE and KD therapy

EXPERIMENTAL

the experimental arm is defined by the addition of the Ketogenic Diet to standard medical therapy

Other: the ketogenic diet; Drug: Standard Medical Therapy

standard care group

ACTIVE COMPARATOR

active comparator arm receives standard medical therapy alone.

Drug: Standard Medical Therapy

Interventions

the ketogenic diet OTHER

First, ketogenic formulation was initiated continuously via naso-enteric tube at 50% of goal and increase to goal (25-30 kcal/kg/day) within 72h. The KD regimen was continued according to seizure control and tolerance before discharge. If the patient was receiving oral nutrition, the modified MAD-KD regimen (carbohydrate 10-20 g/d) was initiated. In addition, if weaning off the diet after discharge, the reduction was 0.5:1 per week.

standard medical therapy for SRSE and KD therapy

Standard Medical Therapy DRUG

Standard Medical Therapy include continuous intravenous infusion of an anesthetic agent, such as midazolam (starting regimen: 0.2 mg/kg IV bolus followed by continuous infusion of 0.1-0.6 mg/kg/h), titrated to seizure termination

standard care group; standard medical therapy for SRSE and KD therapy

Eligibility Criteria

• Age: 14 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients diagnosed with super-refractory status epilepticus (SRSE), in whom status epilepticus (SE) persists or recurs after the initial treatment for SE-including intravenous benzodiazepines, an anti-seizure medication (ASM, such as valproate, levetiracetam, or phenobarbital), and an anesthetic (e.g., propofol) administered continuously for 24 hours-fails to terminate the episode, or when SE recurs upon reduction of the anesthetic.
• Age between 14 and 80 years, regardless of gender.
• The patient's legal guardian has provided signed informed consent.

You may not qualify if:

• Patients with lipid metabolism disorders, including defects in fatty acid transport and beta-oxidation, such as carnitine deficiency (primary) and carnitine-related enzyme deficiencies (including carnitine palmitoyltransferase \[CPT\] I and II deficiency, carnitine translocase deficiency), fatty acid oxidation disorders (including beta-oxidation defects), short-chain acyl-CoA dehydrogenase deficiency (SCAD), medium-chain acyl-CoA dehydrogenase deficiency (MCAD), long-chain acyl-CoA dehydrogenase deficiency (LCAD), long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, medium-chain 3-hydroxyacyl-CoA dehydrogenase deficiency, pyruvate carboxylase deficiency, and porphyria.
• Intolerance to enteral feeding (e.g., intestinal obstruction).
• Receipt of propofol infusion within 24 hours.
• Hemodynamic instability (systolic blood pressure \<90 mmHg or diastolic blood pressure \<60 mmHg, requiring high-dose vasopressors for maintenance).
• Liver failure (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], blood ammonia \>5 times the upper limit of normal; total bilirubin \>10 mg/dL \[171 μmol/L\]).
• Pancreatitis.
• Pregnancy.
• Metabolic instability (blood glucose \<3.1 mmol/L, arterial blood pH \<7.2, serum sodium \<120 or \>160 mmol/L).
• Septic shock.
• Complicated by diabetes insipidus.
• Status epilepticus caused by hypoxic-ischemic brain injury.

Sponsors & Collaborators

• Xuanwu Hospital, Beijing: lead

Study Sites (14)

The First Affiliated Hospital of Anhui Medical University

Hefei, Anhui, 230022, China

RECRUITING

Department of Neurology, Xuanwu Hospital Capital Medical University

Beijing, Beijing Municipality, 100053, China

RECRUITING

Fujian Medical University Union Hospital

Fuzhou, Fujian, 350001, China

RECRUITING

The First Affiliated Hospital of Guangxi Medical University

Nanning, Guangxi, 530021, China

RECRUITING

Guizhou Provincial People's Hospital

Guiyang, Guizhou, 550002, China

RECRUITING

The Second Affiliated Hospital of Hainan Medical University

Haikou, Hainan, 570311, China

NOT YET RECRUITING

The First Hospital of Hebei Medical University

Shijiazhuang, Hebei, 050031, China

RECRUITING

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

RECRUITING

Chifeng Municipal Hospital

Chifeng, Neimenggu, 024000, China

RECRUITING

Qilu Hospital，Shandong University

Jinan, Shandong, 2500012, China

NOT YET RECRUITING

The Second Affiliated Hospital of Zhejiang University School of Medicine

Hanzhou, Zhejiang, 310009, China

RECRUITING

Beijing Tongren Hospital, Capital Medical University

Beijing, 100730, China

NOT YET RECRUITING

The First Hospital of Jilin University

Jilin, 130021, China

RECRUITING

Liaocheng People's Hospital

Liaocheng, 252000, China

RECRUITING

Related Publications (35)

• Singh RK, Joshi SM, Potter DM, Leber SM, Carlson MD, Shellhaas RA. Cognitive outcomes in febrile infection-related epilepsy syndrome treated with the ketogenic diet. Pediatrics. 2014 Nov;134(5):e1431-5. doi: 10.1542/peds.2013-3106.

  PMID: 25332495 BACKGROUND

• Li Y, Yang X, Zhang J, Jiang T, Zhang Z, Wang Z, Gong M, Zhao L, Zhang C. Ketogenic Diets Induced Glucose Intolerance and Lipid Accumulation in Mice with Alterations in Gut Microbiota and Metabolites. mBio. 2021 Mar 30;12(2):e03601-20. doi: 10.1128/mBio.03601-20.

  PMID: 33785628 BACKGROUND

• Nabbout R, Mazzuca M, Hubert P, Peudennier S, Allaire C, Flurin V, Aberastury M, Silva W, Dulac O. Efficacy of ketogenic diet in severe refractory status epilepticus initiating fever induced refractory epileptic encephalopathy in school age children (FIRES). Epilepsia. 2010 Oct;51(10):2033-7. doi: 10.1111/j.1528-1167.2010.02703.x. Epub 2010 Aug 31.

  PMID: 20813015 BACKGROUND

• Wusthoff CJ, Kranick SM, Morley JF, Christina Bergqvist AG. The ketogenic diet in treatment of two adults with prolonged nonconvulsive status epilepticus. Epilepsia. 2010 Jun;51(6):1083-5. doi: 10.1111/j.1528-1167.2009.02388.x. Epub 2009 Oct 20.

  PMID: 19845731 BACKGROUND

• Mahmoud SH, Ho-Huang E, Buhler J. Systematic review of ketogenic diet use in adult patients with status epilepticus. Epilepsia Open. 2019 Nov 24;5(1):10-21. doi: 10.1002/epi4.12370. eCollection 2020 Mar.

  PMID: 32140640 BACKGROUND

• Yudkoff M, Daikhin Y, Horyn O, Nissim I, Nissim I. Ketosis and brain handling of glutamate, glutamine, and GABA. Epilepsia. 2008 Nov;49 Suppl 8(Suppl 8):73-5. doi: 10.1111/j.1528-1167.2008.01841.x.

  PMID: 19049594 BACKGROUND

• Lowe H, Keller AE, Tanzini E, Aimola S, Liu YMC, Zak M, Chan V, Kobayashi J, Donner EJ. Ketonuria and Seizure Control in the Medium Chain Triglyceride and Classic Ketogenic Diets. Can J Neurol Sci. 2022 May;49(3):433-436. doi: 10.1017/cjn.2021.122. Epub 2021 Jun 2.

  PMID: 34075859 BACKGROUND

• Kaul N, Nation J, Laing J, Nicolo JP, Deane AM, Udy AA, Kwan P, O'Brien TJ. Modified low ratio ketogenic therapy in the treatment of adults with super-refractory status epilepticus. JPEN J Parenter Enteral Nutr. 2022 Nov;46(8):1819-1827. doi: 10.1002/jpen.2373. Epub 2022 Apr 7.

  PMID: 35285036 BACKGROUND

• van der Louw E, Aldaz V, Harvey J, Roan M, van den Hurk D, Cross JH, Auvin S; Review Group. Optimal clinical management of children receiving ketogenic parenteral nutrition: a clinical practice guide. Dev Med Child Neurol. 2020 Jan;62(1):48-56. doi: 10.1111/dmcn.14306. Epub 2019 Jul 16.

  PMID: 31313290 BACKGROUND

• Kaul N, Laing J, Nicolo JP, Nation J, Kwan P, O'Brien TJ. Practical Considerations for Ketogenic Diet in Adults With Super-Refractory Status Epilepticus. Neurol Clin Pract. 2021 Oct;11(5):438-444. doi: 10.1212/CPJ.0000000000001009.

  PMID: 34840870 BACKGROUND

• Martin-McGill KJ, Bresnahan R, Levy RG, Cooper PN. Ketogenic diets for drug-resistant epilepsy. Cochrane Database Syst Rev. 2020 Jun 24;6(6):CD001903. doi: 10.1002/14651858.CD001903.pub5.

  PMID: 32588435 BACKGROUND

• Buchhalter JR, D'Alfonso S, Connolly M, Fung E, Michoulas A, Sinasac D, Singer R, Smith J, Singh N, Rho JM. The relationship between d-beta-hydroxybutyrate blood concentrations and seizure control in children treated with the ketogenic diet for medically intractable epilepsy. Epilepsia Open. 2017 May 19;2(3):317-321. doi: 10.1002/epi4.12058. eCollection 2017 Sep.

  PMID: 29588960 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

• van Delft R, Lambrechts D, Verschuure P, Hulsman J, Majoie M. Blood beta-hydroxybutyrate correlates better with seizure reduction due to ketogenic diet than do ketones in the urine. Seizure. 2010 Jan;19(1):36-9. doi: 10.1016/j.seizure.2009.10.009. Epub 2009 Dec 3.

  PMID: 19962324 BACKGROUND

• Breu M, Hafele C, Glatter S, Trimmel-Schwahofer P, Golej J, Male C, Feucht M, Dressler A. Ketogenic Diet in the Treatment of Super-Refractory Status Epilepticus at a Pediatric Intensive Care Unit: A Single-Center Experience. Front Neurol. 2021 Jun 3;12:669296. doi: 10.3389/fneur.2021.669296. eCollection 2021.

  PMID: 34149600 BACKGROUND

• Cervenka MC, Hocker S, Koenig M, Bar B, Henry-Barron B, Kossoff EH, Hartman AL, Probasco JC, Benavides DR, Venkatesan A, Hagen EC, Dittrich D, Stern T, Radzik B, Depew M, Caserta FM, Nyquist P, Kaplan PW, Geocadin RG. Phase I/II multicenter ketogenic diet study for adult superrefractory status epilepticus. Neurology. 2017 Mar 7;88(10):938-943. doi: 10.1212/WNL.0000000000003690. Epub 2017 Feb 8.

  PMID: 28179470 BACKGROUND

• Francis BA, Fillenworth J, Gorelick P, Karanec K, Tanner A. The Feasibility, Safety and Effectiveness of a Ketogenic Diet for Refractory Status Epilepticus in Adults in the Intensive Care Unit. Neurocrit Care. 2019 Jun;30(3):652-657. doi: 10.1007/s12028-018-0653-2.

  PMID: 30484010 BACKGROUND

• Park EG, Lee J, Lee J. The ketogenic diet for super-refractory status epilepticus patients in intensive care units. Brain Dev. 2019 May;41(5):420-427. doi: 10.1016/j.braindev.2018.12.007. Epub 2019 Jan 9.

  PMID: 30638692 BACKGROUND

• Caraballo RH, Flesler S, Armeno M, Fortini S, Agustinho A, Mestre G, Cresta A, Buompadre MC, Escobal N. Ketogenic diet in pediatric patients with refractory focal status epilepticus. Epilepsy Res. 2014 Dec;108(10):1912-6. doi: 10.1016/j.eplepsyres.2014.09.033. Epub 2014 Oct 13.

  PMID: 25454503 BACKGROUND

• Appavu B, Vanatta L, Condie J, Kerrigan JF, Jarrar R. Ketogenic diet treatment for pediatric super-refractory status epilepticus. Seizure. 2016 Oct;41:62-5. doi: 10.1016/j.seizure.2016.07.006. Epub 2016 Jul 21.

  PMID: 27475280 BACKGROUND

• 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

• Thakur KT, Probasco JC, Hocker SE, Roehl K, Henry B, Kossoff EH, Kaplan PW, Geocadin RG, Hartman AL, Venkatesan A, Cervenka MC. Ketogenic diet for adults in super-refractory status epilepticus. Neurology. 2014 Feb 25;82(8):665-70. doi: 10.1212/WNL.0000000000000151. Epub 2014 Jan 22.

  PMID: 24453083 BACKGROUND

• Levy RG, Cooper PN, Giri P. Ketogenic diet and other dietary treatments for epilepsy. Cochrane Database Syst Rev. 2012 Mar 14;(3):CD001903. doi: 10.1002/14651858.CD001903.pub2.

  PMID: 22419282 BACKGROUND

• Neal EG, Chaffe H, Schwartz RH, Lawson MS, Edwards N, Fitzsimmons G, Whitney A, Cross JH. The ketogenic diet for the treatment of childhood epilepsy: a randomised controlled trial. Lancet Neurol. 2008 Jun;7(6):500-6. doi: 10.1016/S1474-4422(08)70092-9. Epub 2008 May 2.

  PMID: 18456557 BACKGROUND

• Goswami JN, Sharma S. Current Perspectives On The Role Of The Ketogenic Diet In Epilepsy Management. Neuropsychiatr Dis Treat. 2019 Nov 25;15:3273-3285. doi: 10.2147/NDT.S201862. eCollection 2019.

  PMID: 31819454 BACKGROUND

• Dahlin M, Hjelte L, Nilsson S, Amark P. Plasma phospholipid fatty acids are influenced by a ketogenic diet enriched with n-3 fatty acids in children with epilepsy. Epilepsy Res. 2007 Feb;73(2):199-207. doi: 10.1016/j.eplepsyres.2006.10.005. Epub 2006 Dec 5.

  PMID: 17150333 BACKGROUND

• Lindefeldt M, Eng A, Darban H, Bjerkner A, Zetterstrom CK, Allander T, Andersson B, Borenstein E, Dahlin M, Prast-Nielsen S. The ketogenic diet influences taxonomic and functional composition of the gut microbiota in children with severe epilepsy. NPJ Biofilms Microbiomes. 2019 Jan 23;5(1):5. doi: 10.1038/s41522-018-0073-2. eCollection 2019.

  PMID: 30701077 BACKGROUND

• Masino SA, Rho JM. Mechanisms of Ketogenic Diet Action. In: Noebels JL, Avoli M, Rogawski MA, Olsen RW, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012. Available from http://www.ncbi.nlm.nih.gov/books/NBK98219/

  PMID: 22787591 BACKGROUND

• Tagliabue A, Ferraris C, Uggeri F, Trentani C, Bertoli S, de Giorgis V, Veggiotti P, Elli M. Short-term impact of a classical ketogenic diet on gut microbiota in GLUT1 Deficiency Syndrome: A 3-month prospective observational study. Clin Nutr ESPEN. 2017 Feb;17:33-37. doi: 10.1016/j.clnesp.2016.11.003. Epub 2016 Dec 18.

  PMID: 28361745 BACKGROUND

• Zhang Y, Zhou S, Zhou Y, Yu L, Zhang L, Wang Y. Altered gut microbiome composition in children with refractory epilepsy after ketogenic diet. Epilepsy Res. 2018 Sep;145:163-168. doi: 10.1016/j.eplepsyres.2018.06.015. Epub 2018 Jun 28.

  PMID: 30007242 BACKGROUND

• Bromfield E, Dworetzky B, Hurwitz S, Eluri Z, Lane L, Replansky S, Mostofsky D. A randomized trial of polyunsaturated fatty acids for refractory epilepsy. Epilepsy Behav. 2008 Jan;12(1):187-90. doi: 10.1016/j.yebeh.2007.09.011.

  PMID: 18086463 BACKGROUND

• Abdallah DM. Anticonvulsant potential of the peroxisome proliferator-activated receptor gamma agonist pioglitazone in pentylenetetrazole-induced acute seizures and kindling in mice. Brain Res. 2010 Sep 10;1351:246-253. doi: 10.1016/j.brainres.2010.06.034. Epub 2010 Jun 21.

  PMID: 20599832 BACKGROUND

• Trinka E, Kalviainen R. 25 years of advances in the definition, classification and treatment of status epilepticus. Seizure. 2017 Jan;44:65-73. doi: 10.1016/j.seizure.2016.11.001. Epub 2016 Nov 14.

  PMID: 27890484 BACKGROUND

• Kantanen AM, Reinikainen M, Parviainen I, Ruokonen E, Ala-Peijari M, Backlund T, Koskenkari J, Laitio R, Kalviainen R. Incidence and mortality of super-refractory status epilepticus in adults. Epilepsy Behav. 2015 Aug;49:131-4. doi: 10.1016/j.yebeh.2015.04.065. Epub 2015 Jul 2.

  PMID: 26141934 BACKGROUND

• Shorvon S, Ferlisi M. The treatment of super-refractory status epilepticus: a critical review of available therapies and a clinical treatment protocol. Brain. 2011 Oct;134(Pt 10):2802-18. doi: 10.1093/brain/awr215. Epub 2011 Sep 13.

  PMID: 21914716 BACKGROUND

Related Links

• Ketogenic diet treatment for super-refractory status epilepticus in the intensive care unit: feasibility, safety and effectiveness

MeSH Terms

Conditions

Status Epilepticus; Encephalitis

Condition Hierarchy (Ancestors)

Seizures; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Diseases; Central Nervous System Diseases; Neuroinflammatory Diseases

Central Study Contacts

Weibi Chen

CONTACT

0086-010-83198424; chenweibi@126.com

Gang Liu

CONTACT

010-83198899; liugangqingyi@sina.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief Physician and associate Professor

Study Record Dates

• First Submitted: December 23, 2024
• First Posted: March 27, 2026
• Study Start: October 20, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: May 15, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (14)