Ketogenic diet for super-refractory status epilepticus

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

This trial will try adding a ketogenic diet given by feeding tube to standard ICU care to stop super-refractory status epilepticus in people aged 14–80.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 84 (estimated)
• Ages: 14 Years to 80 Years
• Sex: All
• Sponsor: Xuanwu Hospital, Beijing (other)
• Locations: 15 sites (Hefei, Anhui and 14 other locations)
• Trial ID: NCT07496749 on ClinicalTrials.gov

What this trial studies

This is a multicenter, randomized, open-label study that assigns eligible ICU patients with super-refractory status epilepticus 1:1 to standard therapy or standard therapy plus a ketogenic diet. The ketogenic diet is delivered by nasogastric tube with a target of 25–30 kcal/kg, started at half strength and advanced to full calories within 72 hours, and non-responders stop the diet after 2 weeks while responders are recommended to continue. The primary outcome is cessation of both clinical and electrographic status epilepticus within 2 weeks as confirmed by continuous EEG, and key secondary outcomes include safety, in-hospital mortality, and feasibility measures such as time to ketosis (blood beta-hydroxybutyrate ≥1.2 mmol/L). All patients in the ketogenic arm receive daily nutritional supplements and the protocol is carried out while patients are hospitalized at the participating centers.

Who should consider this trial

Good fit: Ideal candidates are ICU patients aged 14–80 with super-refractory status epilepticus that persists or recurs after standard antiseizure medications and a continuous anesthetic, whose legal guardian can provide informed consent.

Not a fit: Patients with known disorders of lipid or fatty acid metabolism (for example carnitine or beta-oxidation defects), those unable to receive enteral feeding, or those outside the 14–80 age range are unlikely to qualify or may not receive benefit.

Why it matters

Potential benefit: If successful, adding a ketogenic diet could help stop super-refractory status epilepticus sooner, potentially reducing ICU time, complications, and death.

How similar studies have performed: Prior case series and small uncontrolled studies have reported that ketogenic diets can terminate refractory status epilepticus in some patients, but randomized controlled evidence remains limited.

Eligibility criteria

Inclusion Criteria:

(1) 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;(2) Age between 14 and 80 years, regardless of gender;(3) The patient's legal guardian has provided signed informed consent

Exclusion Criteria:

（1）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.（2）Intolerance to enteral feeding (e.g., intestinal obstruction);（3）Receipt of propofol infusion within 24 hours;（4）Hemodynamic instability (systolic blood pressure \<90 mmHg or diastolic blood pressure \<60 mmHg, requiring high-dose vasopressors for maintenance);（5）Liver failure (aspartate aminotransferase \[AST\], alanine aminotransferase \[ALT\], blood ammonia \>5 times the upper limit of normal; total bilirubin \>10 g/dL \[171 μmol/L\]);（6）Pancreatitis;（7）Pregnancy;（8）Metabolic instability (blood glucose \<3.1 mmol/L, arterial blood pH \<7.2, serum sodium \<120 or \>160 mmol/L);（9）Complicated by sepsis; （10）Complicated by diabetes insipidus;（11）Status epilepticus caused by hypoxic-ischemic brain injury.

Where this trial is running

Hefei, Anhui and 14 other locations

• The First Affiliated Hospital of Anhui Medical University — Hefei, Anhui, China (RECRUITING)
• Department of Neurology, Xuanwu Hospital Capital Medical University — Beijing, Beijing Municipality, China (RECRUITING)
• Fujian Medical University Union Hospital — Fuzhou, Fujian, China (RECRUITING)
• The First Affiliated Hospital of Guangxi Medical University — Nanning, Guangxi, China (RECRUITING)
• Guizhou Provincial People's Hospital — Guiyang, Guizhou, China (RECRUITING)
• The Second Affiliated Hospital of Hainan Medical University — Haikou, Hainan, China (NOT_YET_RECRUITING)
• The First Hospital of Hebei Medical University — Shijiazhuang, Hebei, China (RECRUITING)
• The First Affiliated Hospital of Harbin Medical University — Harbin, Heilongjiang, China (RECRUITING)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, Henan, China (NOT_YET_RECRUITING)
• Chifeng Municipal Hospital — Chifeng, Neimenggu, China (RECRUITING)
• Qilu Hospital，Shandong University — Jinan, Shandong, China (NOT_YET_RECRUITING)
• The Second Affiliated Hospital of Zhejiang University School of Medicine — Hanzhou, Zhejiang, China (RECRUITING)
• Beijing Tongren Hospital, Capital Medical University — Beijing, China (NOT_YET_RECRUITING)
• The First Hospital of Jilin University — Jilin, China (RECRUITING)
• Liaocheng People's Hospital — Liaocheng, China (RECRUITING)

Study contacts

• Study coordinator: Weibi Chen

Conditions: Super-refractory Status Epilepticus, ketogenic diet, status epilepticus, refractory status epilepticus, encephalitis, intensive care unit