Clinical trial NCT02729766: Effects of Empagliflozin an SGLT2-Inhibitor on Healthy Volunteers With Induced Hypotonic Hyponatremia - the DIVE Study
Official title: Effects of Empagliflozin an SGLT2-Inhibitor on Healthy Volunteers With Induced Hypotonic Hyponatremia - the DIVE Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Inappropriate ADH Syndrome
Keywords: Hyponatremia
SGLT2 inhibitor
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2016-04-06
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Informed consent as documented by signature
* Age 18 to 65 years
* serum sodium level 135-145mmol/l
* clinically euvolemic status

Exclusion Criteria:

* 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

Primary outcomes:
measure: 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.
timeFrame: concentration measured every hour within 8 hours after drug administration on both study days
Secondary outcomes:
measure: Serum sodium concentration at every time point of the study
timeFrame: every hour for twelve hours on each of the two study days
measure: Amount of urinary excretion
timeFrame: every 2 hours for twelve hours on each of the two study days
measure: Serum osmolality at every time point of the study
timeFrame: every hour for twelve hours on each of the two study days
measure: Serum glucose at every time point of the study
timeFrame: every hour for twelve hours on each of the two study days
measure: Urinary osmolality
timeFrame: every two hours for twelve hours on each of the two study days
measure: Urinary glucose
timeFrame: every 2 hours for twelve hours on each of the two study days
measure: Serum electrolytes at time point -1, 0, 2 and 8
timeFrame: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
measure: Urinary electrolytes at time point -1, 0, 2 and 8
timeFrame: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
measure: Plasma level of Copeptin at time point -1, 0, 2 and 8
timeFrame: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
measure: Plasma level of Aldosterone at time point -1, 0, 2 and 8
timeFrame: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
measure: Plasma level of Renin at time point -1, 0, 2 and 8
timeFrame: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
measure: Plasma Level of atrial natriuretic peptide (ANP) at time point -1, 0, 2 and 8
timeFrame: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
measure: Plasma levels of brain natriuretic peptide (BNP) at time point -1, 0, 2 and 8
timeFrame: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
measure: Body weight at every time point of the study
timeFrame: every hour during 12 hours on each of the two study days
measure: Blood pressure at every time point of the study
timeFrame: every hour during 12 hours on each of the two study days
measure: Heart rate at every time point of the study
timeFrame: every hour during 12 hours on each of the two study days
measure: Symptoms of hyponatremia assessed by visual analogue scale (VAS) at every time point of the study
timeFrame: every hour during 12 hours on each of the two study days
measure: Urinary sodium level
timeFrame: every 2 hours for twelve hours on each of the two study days
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: Department Endocrinology University Hospital Basel
Study officials:
affiliation: Deputy chief division endocrinology university hospital basel
name: Mirjam Christ-Crain, Prof.
role: PRINCIPAL_INVESTIGATOR
References: