Reduction of Peritoneal Glucose Uptake With Use of SGLT2 in Humans Undergoing Peritoneal Dialysis Treatment. A Proof of Concept Phase 2a Clinical Trial.
试验速览
- 阶段
- 2 期
- 发起方
- 入组人数
- 10
- 试验地点
- 1
- 主要终点
- Peritoneal glucose uptake (mg/ dL)
研究概览
简要总结
End stage renal disease is annually diagnosed in about one thousand patients in Denmark, and one of the treatment modalities in renal replacement therapy is peritoneal dialysis with about 25 % of patients assigned to this treatment (Hommel2010). Peritoneal dialysis is based on the principle of filtering waste products to peritoneal fluid and by exchange of peritoneal fluid eliminate waste products from the body.
In peritoneal dialysis commonly used fluids contain glucose. Exposure to high glucose levels in peritoneal fluid during peritoneal dialysis has several side effects. Primarily, as glucose passes over and into the peritoneal membrane it causes local inflammation which leads to fibrosis over time (Zhou2016). Fibrosis limits the capacity of the exchange of water and waste products over the peritoneal membrane. The decrease of peritoneal exchange capacity is most commonly the reason for termination of peritoneal dialysis.
SGLT2-channels are identified in peritoneal mesothelial cells of rats (Debray-Carcia 2016), and most recently also in humans (Shentu2021). An in vitro model of human peritoneal mesothelial cells incubated with the SGLT2-inhibitor (empagliflozin) has shown significantly decrease in glucose uptake (Zhou2019). Exposure to intraperitoneal empagliflozin in rats, reduced the uptake of glucose over the peritoneal membrane significantly by 78 % and the ultrafiltration was increased (Zhou2019).
Currently, to our knowledge, no clinical trials have been conducted in humans attending peritoneal dialysis with the aim of investigating either the effect or safety of SGLT2i, as it is indeed the first of its kind, with the aim of including participants in peritoneal dialysis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
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
- •Written informed consent
- •Age above 18 years of age
- •In stable peritoneal dialysis for more than 14 days.
排除标准
- •In treatment with SGLT2i currently or within the last 90 days.
- •Treatment for peritoneal infection within the last 30 days.
- •Any hospitalization within the last 30 days.
- •Anaphylaxis to the IMP.
- •Impaired lever function with ALAT above normal range within the last 6 month.
- •Sever efflux problems during peritoneal dialysis for the last 14 days, judged by the investigator.
- •Non-menopausal defined as menstruation within the last 12 month without any other medical cause. Only applicable for female participants.
- •Substance abuse, judged by the investigator.
- •Incapable to follow study protocol, judged by the investigator.
- •Previously included in this clinical trial and exposed to the IMP.
- •Included in another clinical trial with exposure to any IMP within the last 30 days.
研究组 & 干预措施
On treatment
Assigned to oral treatment with dapagliflozin 10 mg for three consecutive days.
干预措施: Dapagliflozin 10 MG [Farxiga] (Drug)
结局指标
主要结局
Peritoneal glucose uptake (mg/ dL)
时间窗: Day 0 (baseline), Day 3 (max dose of treatment)
Glucose level in peritoneal fluid during a four hour standardized peritoneal dialysis. Change in total glucose uptake before and after treatment (treatment periode of three days)
次要结局
- Fluid volume (ml)(Measured at end of each peritoneal dialysis. Peritoneal dialysis done af Day 0, Day 1 (first day of treatment) and day 3 (max dose of treatment))
- Adverse events (events)(At day 1 (first day of treatment), day 3 (max dose of treatment) and day 30 (four weeks after treatment))
- Pharmacokinetics (nmol)(Samples for biobank - samples drawn at end of each peritoneal dialysis. Peritoneal dialysis done af Day 0, Day 1 (first day of treatment) and day 3 (max dose of treatment). Samples are drawn every 30 minuttes during each peritoneal dialysis.)
- Plasma glucose level (mg/ dL)(Measured at end of each peritoneal dialysis. Peritoneal dialysis done af Day 0, Day 1 (first day of treatment) and day 3 (max dose of treatment).)