Randomized, Double-blind, Placebo-controlled Crossover Trial Assessing the Impact of the SGLT2 Inhibitor Empagliflozin on Postprandial Hypoglycaemia After Gastric Bypass
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 22
- 试验地点
- 1
- 主要终点
- Amplitude of change in plasma glucose (difference between peak and nadir plasma glucose concentration in mmol/L) during the mixed meal test.
研究概览
简要总结
Bariatric surgery is an effective anti-obesity treatment providing durable weight loss and profound beneficial effects on glucose metabolism. However, bariatric surgery also comes with an increased risk for a late metabolic complication known as postbariatric hypoglycaemia (PBH). The condition presents with hypoglycaemic episodes 1-3 hours after meals and develops one to several years after bariatric surgery, mainly gastric bypass. PBH affects approximately 30% of patients without preexisting diabetes. For a subset of patients, hypoglycaemia-associated impairment of daily living and social functioning are commonly observed. The underlying mechanisms of PBH are multifactorial. It is considered that inadequately high insulin secretion caused by both accelerated glucose absorption from the gut and increased insulinotropic hormones such as GLP-1 are important pathophysiologic mechanisms. Empagliflozin, a sodium-glucose cotransporter 2 (SGLT2) inhibitor reduces glucose exposure by increasing urinary glucose excretion. In a pilot study, a single dose of 10mg of empagliflozin taken before a mixed meal reduced the risk of PBH by 74%. Both, postprandial glucose and insulin exposure were significantly lower with empagliflozin vs. placebo, which makes Empagliflozin a potential treatment for PBH. In this study, treatment naïve patients will be randomized to receive either oral empagliflozin 25 mg daily in the morning for 20 days, followed by 2-6 weeks wash out and 20 days placebo once daily in the morning, or the reverse sequence. Urine and blood analysis will be performed as detailed in the protocol.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Informed Consent as documented by signature
- •Age 18 years or older
- •Gastric bypass surgery ≥1 year ago
- •Biochemically confirmed postprandial hypoglycaemia (plasma or sensor glucose <3.0mmol/l) within the past three months
排除标准
- •Diabetes on anti-diabetic treatment (insulin and/or non-insulin agents)
- •Genito-urinary infection, if not treated successfully
- •Chronic kidney disease (defined as CKD-EPI eGFR < 60 mL/min per 1.73 m2 body surface area)
- •Pregnant and lactating women (urine pregnancy test to be performed for women of childbearing potential [defined as women who are not surgically sterilized/ hysterectomized, and/ or who are postmenopausal for less than 12 months]) or women of childbearing potential that refuse to use an effective contraceptive method [birth control pill or intrauterine device (IUD)]).
- •Inability to understand and follow the protocol
- •Known allergy to the study drug
- •Participation in another interventional clinical trial overlapping with the current trial
研究组 & 干预措施
Empagliflozin first, Placebo second
Oral empagliflozin 25 mg daily in the morning for 20 days, followed by oral placebo (daily in the morning) for 20 days after a wash-out period of 2-6 weeks
干预措施: Empagliflozin 25 MG (Drug)
Empagliflozin first, Placebo second
Oral empagliflozin 25 mg daily in the morning for 20 days, followed by oral placebo (daily in the morning) for 20 days after a wash-out period of 2-6 weeks
干预措施: Placebo (Drug)
Placebo first, Empagliflozin second
Oral placebo (daily in the morning) for 20 days, followed by oral empagliflozin 25 mg daily in the morning for 20 days after a wash-out period of 2-6 weeks
干预措施: Empagliflozin 25 MG (Drug)
Placebo first, Empagliflozin second
Oral placebo (daily in the morning) for 20 days, followed by oral empagliflozin 25 mg daily in the morning for 20 days after a wash-out period of 2-6 weeks
干预措施: Placebo (Drug)
结局指标
主要结局
Amplitude of change in plasma glucose (difference between peak and nadir plasma glucose concentration in mmol/L) during the mixed meal test.
时间窗: The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period).
On day 20 of the intake of either empagliflozin or placebo, participants undergo a mixed meal test. During the test, the amplitude of plasma glucose (difference between peak and nadir plasma glucose concentration in mmol/L) will be measured.
次要结局
- Proportion of participants experiencing hypoglycaemia (defined as plasma glucose<3.0mmol/L) during the mixed meal tolerance test(The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period).)
- Nadir plasma glucose during mixed meal test(The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period).)
- Mean amplitude of glucose excursion (MAGE) based on CGM glucose(The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded.)
- Percent time spent with CGM glucose >10.0mmol/L(The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded.)
- Percent time spent with CGM glucose <3.0mmol/L(The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded.)
- Percent time spent with CGM glucose <2.8mmol/L(The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded.)
- Peak plasma glucose during mixed meal test(The outcome will be assessed during the mixed-meal test on the day of the experimental visit at the end of each study period (day 20-24 of the respective study period).)
- Frequency of postprandial symptoms based on a modified Edinburgh Hypoglycaemia(The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo.)
- Mean coefficient of variability based on CGM glucose(The outcome will be calculated from day 1 to day 20 of intake of IMP/Placebo (i.e. aggregated measures of the outcome will be calculated for each period). The first 3 days of data of each period will be discarded.)