KD Treatment for Super-refractory Status Epilepticus (KD)

May 12, 2026 updated by: Weibi Chen, Xuanwu Hospital, Beijing

Ketogenic Diet Treatment for Super-refractory Status Epilepticus: a Multicenter, Prospective, Randomized, Controlled Trial

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).

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter, prospective, randomized, controlled, open-label clinical study to evaluate the efficacy and safety of ketogenic diet (KD) as an adjunctive therapy in patients with Super Refractory Status Epilepticus (SRSE).

The study plans to enroll eligible SRSE patients. Participants will be randomly assigned in a 1:1 ratio to one of two groups:

  1. Control Group: Receives standard medical therapy according to current guideline recommendations for SRSE management.
  2. Intervention Group: Receives standard medical therapy plus a ketogenic diet intervention.

The KD intervention will be administered via a nasogastric tube using a ketogenic formula. The nutritional goal is 25-30 kcal/kg, initiated at half-strength and advanced to the full caloric target within 72 hours. If no clinical improvement is observed within 2 weeks of initiating the KD, it will be discontinued. For responders, continuation is recommended. All patients in the KD group will receive concomitant daily nutritional supplements.

The primary outcome measure is the efficacy of controlling SRSE within 2 weeks after randomization. Efficacy is defined as the cessation of both clinical and electrographic status epilepticus, as confirmed by continuous EEG monitoring.

Key secondary outcomes include:

  • Safety evaluation, including all KD-related adverse events and in-hospital mortality.
  • Feasibility of KD (time to achieve ketosis, defined as blood beta-hydroxybutyrate level ≥1.2 mmol/L or urine ketones 1+).
  • Neurological and functional outcomes assessed by the modified Rankin Scale (mRS), Glasgow Outcome Scale-Extended (GOS-E), and quality of life (QOLIE-31) at discharge, 3 months, and 6 months.
  • Cognitive function (MMSE, MoCA) at 3 and 6 months. Statistical analysis will be performed on both the Full Analysis Set (FAS) and the Per-Protocol Set (PPS).

Study Type

Interventional

Enrollment (Estimated)

84

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • China
      • Beijing, China, 100730
        • Not yet recruiting
        • Beijing Tongren Hospital, Capital Medical University
        • Contact:
      • Jilin, China, 130021
        • Recruiting
        • The First Hospital of Jilin University
        • Contact:
      • Liaocheng, China, 252000
        • Recruiting
        • Liaocheng People's Hospital
        • Contact:
    • Anhui
      • Hefei, Anhui, China, 230022
        • Recruiting
        • The First Affiliated Hospital of Anhui Medical University
        • Contact:
    • Beijing Municipality
      • Beijing, Beijing Municipality, China, 100053
        • Recruiting
        • Department of Neurology, Xuanwu Hospital Capital Medical University
        • Contact:
    • Fujian
      • Fuzhou, Fujian, China, 350001
        • Recruiting
        • Fujian Medical University Union Hospital
        • Contact:
    • Guangxi
      • Nanning, Guangxi, China, 530021
        • Recruiting
        • The First Affiliated Hospital of Guangxi Medical University
        • Contact:
    • Guizhou
      • Guiyang, Guizhou, China, 550002
        • Recruiting
        • Guizhou Provincial People's Hospital
        • Contact:
    • Hainan
      • Haikou, Hainan, China, 570311
        • Not yet recruiting
        • The Second Affiliated Hospital of Hainan Medical University
        • Contact:
    • Hebei
      • Shijiazhuang, Hebei, China, 050031
        • Recruiting
        • The First Hospital of Hebei Medical University
        • Contact:
    • Heilongjiang
      • Harbin, Heilongjiang, China, 150001
        • Recruiting
        • The First Affiliated Hospital of Harbin Medical University
        • Contact:
    • Neimenggu
      • Chifeng, Neimenggu, China, 024000
        • Recruiting
        • Chifeng Municipal Hospital
        • Contact:
    • Shandong
      • Jinan, Shandong, China, 2500012
        • Not yet recruiting
        • Qilu Hospital，Shandong University
        • Contact:
    • Zhejiang
      • Hanzhou, Zhejiang, China, 310009
        • Recruiting
        • The Second Affiliated Hospital of Zhejiang University School of Medicine
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: standard medical therapy for SRSE and KD therapy
the experimental arm is defined by the addition of the Ketogenic Diet to standard medical therapy
Other: the ketogenic diet
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.
Drug: Standard Medical Therapy
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
Active Comparator: standard care group
active comparator arm receives standard medical therapy alone.
Drug: Standard Medical Therapy
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Time to cessation of SRSE
Time Frame: 2 weeks

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Xuanwu Hospital, Beijing

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 20, 2025

Primary Completion (Estimated)

February 1, 2027

Study Completion (Estimated)

March 1, 2027

Study Registration Dates

First Submitted

December 23, 2024

First Submitted That Met QC Criteria

March 22, 2026

First Posted (Actual)

March 27, 2026

Study Record Updates

Last Update Posted (Actual)

May 15, 2026

Last Update Submitted That Met QC Criteria

May 12, 2026

Last Verified

March 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KS2025230-001

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

The individual participant data (IPD) generated in this study contains sensitive clinical information. To ensure the confidentiality and privacy of our participants as mandated by Chinese regulations and our institutional ethics committee, the raw data cannot be made publicly available. The datasets are also subject to ongoing analyses by the research team for secondary endpoints and future studies. However, anonymized data supporting the main findings can be made available from the corresponding author upon reasonable request, subject to review and approval by the study's steering committee and a signed data access agreement.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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