Effects of the SGLT2 Inhibitor Empagliflozin on Renal Tissue Oxygenation in Non-diabetic Subjects
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Renal oxygenation
研究概览
简要总结
SGLT-2 inhibitors belong to a new class of hypoglycemic drugs with the unique property of decreasing blood glucose through an increase in glucosuria. These drugs inhibit the sodium glucose transporter 2 (SGLT2) expressed at the luminal membrane of the proximal tubule.
SGLT-2 inhibition in type 2 diabetic subjects and in healthy volunteers shifts the threshold for renal glucose excretion to lower levels. This effect is independent from insulin. The inhibition of SGLT2 decreases HbA1C, systolic blood pressure and weight in diabetic subjects. Recently, the EMPA-REG trial demonstrated a decrease in cardiovascular mortality and renal endpoints in empagliflozin treated type 2 diabetic patients with established cardio-vascular disease.
Because this novel hypoglycemic drug has unique and direct effects on renal tissue metabolism, it is important to better examine its effects on the kidney. With this study, we propose to explore the effects of empagliflozin on renal tissue oxygenation. Our hypothesis is that SGLT-2 inhibition decreases renal cortical energy requirements with consequently an increase in renal tissue oxygenation.
详细描述
This study is a double-blind, randomized, placebo-controlled study that will examine the acute and chronic renal effects of empagliflozin in healthy volunteers.
A total of 45 healthy volunteers will be included in the study: 15 normal weight, 15 overweight (BMI: 25-30kg/m2) and 15 obese (BMI>30kg/m2) non diabetic subjects (as determined after an oral glucose tolerance test).
Empagliflozin 10mg vs placebo will be administered in a blinded fashion qd. The acute and chronic renal response to empagliflozin will be assessed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Placebo and Empagliflozin pills
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Normal weight (BMI: 19-24.9kg/m2), overweight (BMI:25-30kg/m2) or obesity (BMI>30kg/m2)
- •Men and women (with a negative pregnancy test) during the follicular phase of the menstrual cycle. All groups will have a balanced number of men and women.
- •OGTT/HbA1C: normal or pre-diabetes
- •eGFR>60ml/min, albumin/creatinine ratio <3.3mg/mmol (<30 mg/g)
- •Signed consent form
- •Normal renal ultrasound
- •Normal urine dipstick
排除标准
- •Antihypertensive therapy
- •NSAID treatment
- •Former bariatric surgery
- •Age<18y or >50y
- •At risk of dehydration or hypotension
- •Past history of recurrent genital or urinary tract infections
- •Contra-indication for MR imaging (pacemaker or other implanted metallic device, claustrophobia)
- •Pregnancy
- •Sustained systolic blood pressure >150mmHg or diastolic blood pressure >95mmHg
研究组 & 干预措施
empagliflozin 10mg
Empagliflozin (Jardiance) 10mg is an SGLT-2inhibitor. The drug will be taken qd for 4 weeks.
干预措施: Empagliflozin 10 mg (Drug)
Placebo
Placebo will be taken qd for 4 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Renal oxygenation
时间窗: 18 months
The acute and chronic effect of empagliflozin on renal oxygenation will be assessed by BOLD-MRI
次要结局
- Acute and chronic effects of empagliflozin on renal resistance indexes and renal volume after 4 weeks treatment(18 months)
- Effect of body weight on the renal response to empagliflozin(18 months)
- Acute and chronic effects of empagliflozin on diurnal and nocturnal sodium, potassium, uric acid, calcium, phosphate, glucose and lithium clearances after 4 weeks treatment(18 months)
- Effects of empagliflozin on 24h blood pressure mesaurements(18 months)
研究者
Michel Burnier
Professor
Centre Hospitalier Universitaire Vaudois