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

NCT05512130 | Unknown Early Phase 1 DMC FDA Drug

• 1 other identifier: FBJH Grant ID 5936
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

Epilepsy

Outcome Measures

Primary Outcomes (3)

• Change in blood beta-hydroxybutyrate while on empagliflozin

  For each participant, calculate the difference between the blood beta-hydroxybutyrate after two weeks on empagliflozin and after two weeks on placebo.

  2 weeks

• Change in blood glucose while on empagliflozin

  For each participant, calculate the difference between the blood glucose after two weeks on empagliflozin and after two weeks on placebo.

  2 weeks

• Number of participants with adverse effects from empagliflozin

  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.

  2 weeks

Secondary Outcomes (1)

• Change in seizure frequency

  2 weeks

Study Arms (2)

Empagliflozin / Placebo

EXPERIMENTAL

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

Drug: Empagliflozin 25 mg; Drug: Placebo

Placebo / Empagliflozin

EXPERIMENTAL

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

Drug: Empagliflozin 25 mg; Drug: Placebo

Interventions

Empagliflozin 25 mg DRUG

Participants will take empagliflozin daily for 2 weeks.

Also known as: Jardiance

Empagliflozin / Placebo; Placebo / Empagliflozin

Placebo DRUG

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

Empagliflozin / Placebo; Placebo / Empagliflozin

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• 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%

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Related Publications (9)

• Kossoff EH, Krauss GL, McGrogan JR, Freeman JM. Efficacy of the Atkins diet as therapy for intractable epilepsy. Neurology. 2003 Dec 23;61(12):1789-91. doi: 10.1212/01.wnl.0000098889.35155.72.

  PMID: 14694049 BACKGROUND

• Pfeifer HH, Thiele EA. Low-glycemic-index treatment: a liberalized ketogenic diet for treatment of intractable epilepsy. Neurology. 2005 Dec 13;65(11):1810-2. doi: 10.1212/01.wnl.0000187071.24292.9e.

  PMID: 16344529 BACKGROUND

• Rho JM, Sankar R. The ketogenic diet in a pill: is this possible? Epilepsia. 2008 Nov;49 Suppl 8(Suppl 8):127-33. doi: 10.1111/j.1528-1167.2008.01857.x.

  PMID: 19049610 BACKGROUND

• Stafstrom CE, Roopra A, Sutula TP. Seizure suppression via glycolysis inhibition with 2-deoxy-D-glucose (2DG). Epilepsia. 2008 Nov;49 Suppl 8:97-100. doi: 10.1111/j.1528-1167.2008.01848.x.

  PMID: 19049601 BACKGROUND

• Stafstrom CE, Ockuly JC, Murphree L, Valley MT, Roopra A, Sutula TP. Anticonvulsant and antiepileptic actions of 2-deoxy-D-glucose in epilepsy models. Ann Neurol. 2009 Apr;65(4):435-47. doi: 10.1002/ana.21603.

  PMID: 19399874 BACKGROUND

• Ferrannini E, Baldi S, Frascerra S, Astiarraga B, Heise T, Bizzotto R, Mari A, Pieber TR, Muscelli E. Shift to Fatty Substrate Utilization in Response to Sodium-Glucose Cotransporter 2 Inhibition in Subjects Without Diabetes and Patients With Type 2 Diabetes. Diabetes. 2016 May;65(5):1190-5. doi: 10.2337/db15-1356. Epub 2016 Feb 9.

  PMID: 26861783 BACKGROUND

• Kossoff EH, Zupec-Kania BA, Auvin S, Ballaban-Gil KR, Christina Bergqvist AG, Blackford R, Buchhalter JR, Caraballo RH, Cross JH, Dahlin MG, Donner EJ, Guzel O, Jehle RS, Klepper J, Kang HC, Lambrechts DA, Liu YMC, Nathan JK, Nordli DR Jr, Pfeifer HH, Rho JM, Scheffer IE, Sharma S, Stafstrom CE, Thiele EA, Turner Z, Vaccarezza MM, van der Louw EJTM, Veggiotti P, Wheless JW, Wirrell EC; Charlie Foundation; Matthew's Friends; Practice Committee of the Child Neurology Society. Optimal clinical management of children receiving dietary therapies for epilepsy: Updated recommendations of the International Ketogenic Diet Study Group. Epilepsia Open. 2018 May 21;3(2):175-192. doi: 10.1002/epi4.12225. eCollection 2018 Jun.

  PMID: 29881797 BACKGROUND

• Biester T, Kordonouri O, Danne T. Beyond type 2 diabetes: sodium glucose co-transporter-inhibition in type 1 diabetes. Diabetes Obes Metab. 2019 Apr;21 Suppl 2:53-61. doi: 10.1111/dom.13659.

  PMID: 31081591 BACKGROUND

• 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.

  PMID: 32358544 BACKGROUND

MeSH Terms

Conditions

Epilepsy

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Kwee L Thio

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kwee L Thio, MD, PhD

CONTACT

314-454-6120; thiol@wustl.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, placebo-controlled, double-blinded, crossover trial

Study Record Dates

• First Submitted: July 5, 2022
• First Posted: August 23, 2022
• Study Start: August 17, 2022
• Primary Completion: March 1, 2023
• Study Completion: June 30, 2023
• Last Updated: August 23, 2022

Record last verified: 2022-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: For 3 years beginning one year after study closure
• Access Criteria: Qualified investigators upon request.

Locations

US (1)