Effects of Empagliflozin an SGLT2-Inhibitor on Healthy Volunteers With Induced Hypotonic Hyponatremia - the DIVE Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 15
- 试验地点
- 1
- 主要终点
- The primary outcome is the area under the curve (AUC) of the serum sodium concentration between time points 2 and 8 hours after administration of the study drug.
研究概览
简要总结
Empagliflozin (Jardiance)® is a sodium glucose co-transporter 2 (SGLT2)-Inhibitor, which is a new treatment option developed for patients with diabetes mellitus type 2. The SGLT2 is expressed in the proximal tubule and reabsorbs approximately 90 percent of the filtered glucose. The inhibition of SGLT2 results in renal excretion of glucose with subsequent osmotic diuresis. This mechanism could result in a therapeutic effect in patients with hypotonic hyponatremia as in the syndrome of inappropriate antidiuretic hormone (ADH) secretion (SIAD). Because patients with SIAD usually have several comorbidities and different medications, studies investigating the physiological effects are difficult to interpret. Therefore a model to study the possible physiological effect of SGLT2-inhibitors in hypotonic hyponatremia as in SIAD is needed.
The aim of this study is to evaluate whether empagliflozin (Jardiance)® has an effect on serum sodium levels of healthy volunteers with induced hypotonic hyponatremia.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Informed consent as documented by signature
- •Age 18 to 65 years
- •serum sodium level 135-145mmol/l
- •clinically euvolemic status
排除标准
- •Known or suspected allergy to trial product or related products
- •Pregnancy or breast feeding
- •Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
- •Participation in another study with investigational drug within the 30 days preceding and during the present study
- •Enrolment of the investigator, his/her family members, employees and other dependent persons
- •untreated hypothyroidism
- •cortisol deficiency
- •history of heart failure
- •liver cirrhosis at any stage
- •kidney disease (GFR <60ml/min)
- •epileptic seizures within the last year
- •uncontrolled hypertension (systolic blood pressure >160mmHg)
- •Diabetes mellitus type 1 or 2
- •BMI <18 or >29kg/m2
- •other severe disease
研究组 & 干预措施
Empagliflozin 25mg Tbl
Induced hypotonic hyponatremia - SIAD model: Hypotonic hyponatremia will be induced in healthy volunteers through oral overhydration and parenteral administration of desmopressin (Minirin)® 4ug. After administration of the study drug, the artificial SIAD will be sustained with infusion of hypotonic sodium-solution (NaCl 0.45%) over two hours.
干预措施: Induced hypotonic hyponatremia - SIAD model (Other)
Empagliflozin 25mg Tbl
Induced hypotonic hyponatremia - SIAD model: Hypotonic hyponatremia will be induced in healthy volunteers through oral overhydration and parenteral administration of desmopressin (Minirin)® 4ug. After administration of the study drug, the artificial SIAD will be sustained with infusion of hypotonic sodium-solution (NaCl 0.45%) over two hours.
干预措施: Empagliflozin 25mg Tbl (Drug)
Placebo P-Tablet
Induced hypotonic hyponatremia - SIAD model: Hypotonic hyponatremia will be induced in healthy volunteers through oral overhydration and parenteral administration of desmopressin (Minirin)® 4ug. After administration of the study drug, the artificial SIAD will be sustained with infusion of hypotonic sodium-solution (NaCl 0.45%) over two hours.
干预措施: Induced hypotonic hyponatremia - SIAD model (Other)
Placebo P-Tablet
Induced hypotonic hyponatremia - SIAD model: Hypotonic hyponatremia will be induced in healthy volunteers through oral overhydration and parenteral administration of desmopressin (Minirin)® 4ug. After administration of the study drug, the artificial SIAD will be sustained with infusion of hypotonic sodium-solution (NaCl 0.45%) over two hours.
干预措施: Placebo P-Tablet (Drug)
结局指标
主要结局
The primary outcome is the area under the curve (AUC) of the serum sodium concentration between time points 2 and 8 hours after administration of the study drug.
时间窗: concentration measured every hour within 8 hours after drug administration on both study days
次要结局
- Urinary glucose(every 2 hours for twelve hours on each of the two study days)
- Serum osmolality at every time point of the study(every hour for twelve hours on each of the two study days)
- Plasma level of Aldosterone at time point -1, 0, 2 and 8(1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day)
- Plasma Level of atrial natriuretic peptide (ANP) at time point -1, 0, 2 and 8(1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day)
- Heart rate at every time point of the study(every hour during 12 hours on each of the two study days)
- Serum sodium concentration at every time point of the study(every hour for twelve hours on each of the two study days)
- Serum glucose at every time point of the study(every hour for twelve hours on each of the two study days)
- Symptoms of hyponatremia assessed by visual analogue scale (VAS) at every time point of the study(every hour during 12 hours on each of the two study days)
- Amount of urinary excretion(every 2 hours for twelve hours on each of the two study days)
- Urinary osmolality(every two hours for twelve hours on each of the two study days)
- Urinary electrolytes at time point -1, 0, 2 and 8(1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day)
- Blood pressure at every time point of the study(every hour during 12 hours on each of the two study days)
- Urinary sodium level(every 2 hours for twelve hours on each of the two study days)
- Serum electrolytes at time point -1, 0, 2 and 8(1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day)
- Plasma level of Copeptin at time point -1, 0, 2 and 8(1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day)
- Plasma level of Renin at time point -1, 0, 2 and 8(1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day)
- Body weight at every time point of the study(every hour during 12 hours on each of the two study days)
- Plasma levels of brain natriuretic peptide (BNP) at time point -1, 0, 2 and 8(1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day)