Clinical trial NCT05512130: Sodium-Glucose Cotransporter-2 Inhibitors: A Potential Novel Treatment for Epilepsy
Official title: Sodium-Glucose Cotransporter-2 Inhibitors: A Potential Novel Treatment for Epilepsy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: EARLY_PHASE1
Conditions: Epilepsy
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2022-08-23
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized, placebo-controlled, double-blinded, crossover trial
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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%

Primary outcomes:
measure: Change in blood beta-hydroxybutyrate while on empagliflozin
timeFrame: 2 weeks
measure: Change in blood glucose while on empagliflozin
timeFrame: 2 weeks
measure: Number of participants with adverse effects from empagliflozin
timeFrame: 2 weeks
Secondary outcomes:
measure: Change in seizure frequency
timeFrame: 2 weeks
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Kwee L Thio
role: PRINCIPAL_INVESTIGATOR
References:
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