Epilepsy
Conditions
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.
Interventions
DRUGEmpagliflozin 25 mg
Participants will take empagliflozin daily for 2 weeks.
DRUGPlacebo
Participants will take a placebo daily for 2 weeks. The placebo will be identical to empagliflozin in appearance.
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, placebo-controlled, double-blinded, crossover trial
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
No
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%
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in blood beta-hydroxybutyrate while on empagliflozin | 2 weeks | For each participant, calculate the difference between the blood beta-hydroxybutyrate after two weeks on empagliflozin and after two weeks on placebo. |
| Change in blood glucose while on empagliflozin | 2 weeks | For each participant, calculate the difference between the blood glucose after two weeks on empagliflozin and after two weeks on placebo. |
| Number of participants with adverse effects from empagliflozin | 2 weeks | For each participant, calculate the difference in weight, blood pressure, and pulse after two weeks on empagliflozin and after two weeks on placebo. Compare the number of participants having an abnormal complete blood count, comprehensive metabolic panel, hemoglobin A1c, magnesium, phosphorus, and urinalysis after two weeks on empagliflozin and after two weeks on placebo. Compare the number of participants who have increased urination and genital irritation after two weeks on empagliflozin and after two weeks on placebo. Will determine the number of participants with a clinically significant change in any of the listed parameters after two weeks on empagliflozin. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in seizure frequency | 2 weeks | For each participant, calculate the difference in seizure frequency as determined by seizure diaries during the two weeks on empagliflozin and the two weeks on placebo. |
Countries
United States
Contacts
Primary ContactKwee L Thio, MD, PhD
Outcome results
None listed