Sodium-Glucose Cotransporter-2 Inhibitors: A Potential Novel Treatment for Epilepsy

The Washington University

Status and phase: Enrolling; Early Phase 1

Conditions: Epilepsy

Treatments: Drug: Empagliflozin 25 mg; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT05512130

FBJH Grant ID 5936

Details and patient eligibility

About

About 30% of persons with epilepsy have seizures that do not respond to drugs. The ketogenic diet is an effective treatment option for them, but this high fat diet is strict and difficult to maintain. The properties of gliflozins, which often are used to treat type 2 diabetes, make them a potential replacement for the ketogenic diet. This pilot study will determine whether gliflozins induce ketosis and could be used to treat adults with epilepsy safely.

Full description

The 30% of persons with epilepsy who are drug-resistant bear most of the financial and psychosocial costs of this common neurological disorder. An effective, clinically used treatment for these individuals is the ketogenic diet, a high fat, low carbohydrate diet. Newer variants of the ketogenic diet including the modified Atkins diet (MAD) and low glycemic index treatment (LGIT) are more palatable than the older versions but are challenging to maintain because they are strict. The MAD and LGIT lower blood glucose and produce mild ketosis. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) such as empagliflozin have become important additions to the armamentarium for treating type 2 diabetes. SGLT2i decrease blood sugar by causing glucosuria, and they induce mild ketosis. These actions raise the possibility that SGLT2i can replace the MAD and LGIT as epilepsy treatments. This pilot, phase 1 study will determine the feasibility, safety, and tolerability of the SGLT2i empagliflozin in adults with epilepsy.

Enrollment: 18 estimated patients

Sex: All

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Age 18-45 years
• Focal, generalized, combined generalized and focal, or unknown epilepsy type
• Drug-responsive or drug-resistant epilepsy

Exclusion criteria

• Seizure frequency >2 seizures per day during the 6 months prior to enrollment
• Status epilepticus during the 2 years prior to enrollment
• Taking a gliflozin
• Allergy to gliflozins
• Taking a carbonic anhydrase inhibitor such as acetazolamide
• On any ketogenic diet variant
• Having an absolute contraindication to a ketogenic diet
• Type 1 or type 2 diabetes
• Pregnancy
• Moderate to severe intellectual disability,
• Significant cardiovascular disease
• Renal insufficiency
• Body mass index <18.5 or ≥30
• Hemoglobin A1c ≥5.7%

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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18 participants in 2 patient groups

Empagliflozin / Placebo

Experimental group

Description:

Participants randomized to this arm will receive 25 mg of empagliflozin daily for 2 weeks followed placebo daily for 2 weeks

Treatment:

Drug: Placebo

Drug: Empagliflozin 25 mg

Placebo / Empagliflozin

Experimental group

Description:

Participants randomized to this arm will receive placebo daily for 2 weeks followed by 25 mg of empagliflozin daily for 2 weeks

Treatment:

Drug: Placebo

Drug: Empagliflozin 25 mg