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

NCT ID: NCT05512130

Last Updated: 2022-08-23

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-17
• Study Completion Date: 2023-06-30

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.

Conditions

Epilepsy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Empagliflozin / Placebo

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

Group Type: EXPERIMENTAL

Empagliflozin 25 mg

Intervention Type: DRUG

Participants will take empagliflozin daily for 2 weeks.

Placebo

Intervention Type: DRUG

Participants will take a placebo daily for 2 weeks. The placebo will be identical to empagliflozin in appearance.

Placebo / Empagliflozin

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

Group Type: EXPERIMENTAL

Empagliflozin 25 mg

Intervention Type: DRUG

Participants will take empagliflozin daily for 2 weeks.

Placebo

Intervention Type: DRUG

Participants will take a placebo daily for 2 weeks. The placebo will be identical to empagliflozin in appearance.

Interventions

Empagliflozin 25 mg

Participants will take empagliflozin daily for 2 weeks.

Intervention Type: DRUG

Placebo

Participants will take a placebo daily for 2 weeks. The placebo will be identical to empagliflozin in appearance.

Intervention Type: DRUG

Other Intervention Names

Jardiance

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%

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Kwee L Thio

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University

St Louis, Missouri, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Kwee L Thio, MD, PhD

Role: CONTACT

thiol@wustl.edu

314-454-6120

Facility Contacts

Kwee L Thio, MD, PhD

Role: primary

thiol@wustl.edu

314-454-6120

References

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

PMID: 16344529 (View on PubMed)

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Reference Type: BACKGROUND

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Kim SR, Lee SG, Kim SH, Kim JH, Choi E, Cho W, Rim JH, Hwang I, Lee CJ, Lee M, Oh CM, Jeon JY, Gee HY, Kim JH, Lee BW, Kang ES, Cha BS, Lee MS, Yu JW, Cho JW, Kim JS, Lee YH. SGLT2 inhibition modulates NLRP3 inflammasome activity via ketones and insulin in diabetes with cardiovascular disease. Nat Commun. 2020 May 1;11(1):2127. doi: 10.1038/s41467-020-15983-6.

Reference Type: BACKGROUND

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Other Identifiers

FBJH Grant ID 5936

Identifier Type: -

Identifier Source: org_study_id