Sodium-Glucose Cotransporter-2 Inhibitors: A Potential Novel Treatment for Epilepsy
试验速览
- 阶段
- 早期 1 期
- 入组人数
- 18
- 试验地点
- 1
- 主要终点
- Change in blood beta-hydroxybutyrate while on empagliflozin
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-45 years
- •Focal, generalized, combined generalized and focal, or unknown epilepsy type
- •Drug-responsive or drug-resistant epilepsy
排除标准
- •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%
研究组 & 干预措施
Placebo / Empagliflozin
Participants randomized to this arm will receive placebo daily for 2 weeks followed by 25 mg of empagliflozin daily for 2 weeks
干预措施: Empagliflozin 25 mg (Drug)
Empagliflozin / Placebo
Participants randomized to this arm will receive 25 mg of empagliflozin daily for 2 weeks followed placebo daily for 2 weeks
干预措施: Empagliflozin 25 mg (Drug)
Empagliflozin / Placebo
Participants randomized to this arm will receive 25 mg of empagliflozin daily for 2 weeks followed placebo daily for 2 weeks
干预措施: Placebo (Drug)
Placebo / Empagliflozin
Participants randomized to this arm will receive placebo daily for 2 weeks followed by 25 mg of empagliflozin daily for 2 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Change in blood beta-hydroxybutyrate while on empagliflozin
时间窗: 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
时间窗: 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
时间窗: 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.
次要结局
- Change in seizure frequency(2 weeks)