Clinical Trial: Effects of Empagliflozin an SGLT2-Inhibitor on Healthy Volunteers With Induced Hypotonic Hyponatremia - the DIVE Study

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Effects of Empagliflozin an SGLT2-Inhibitor on Healthy Volunteers With Induced Hypotonic Hyponatremia - the DIVE Study

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.


Detailed Summary:
Sponsor: University Hospital, Basel, Switzerland

Current Primary Outcome: 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. [ Time Frame: concentration measured every hour within 8 hours after drug administration on both study days ]

Original Primary Outcome: serum sodium concentration after 7 hours of study medication administration [ Time Frame: 7 hours ]

Current Secondary Outcome:

  • Serum sodium concentration at every time point of the study [ Time Frame: every hour for twelve hours on each of the two study days ]
  • Amount of urinary excretion [ Time Frame: every 2 hours for twelve hours on each of the two study days ]
  • Serum osmolality at every time point of the study [ Time Frame: every hour for twelve hours on each of the two study days ]
  • Serum glucose at every time point of the study [ Time Frame: every hour for twelve hours on each of the two study days ]
  • Urinary osmolality [ Time Frame: every two hours for twelve hours on each of the two study days ]
  • Urinary glucose [ Time Frame: every 2 hours for twelve hours on each of the two study days ]
  • Serum electrolytes at time point -1, 0, 2 and 8 [ Time Frame: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day ]
  • Urinary electrolytes at time point -1, 0, 2 and 8 [ Time Frame: 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 [ Time Frame: 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 Aldosterone at time point -1, 0, 2 and 8 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day ]
  • Plasma levels of brain natriuretic peptide (BNP) at time point -1, 0, 2 and 8 [ Time Frame: 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 [ Time Frame: every hour during 12 hours on each of the two study days ]
  • Blood pressure at every time point of the study [ Time Frame: every hour during 12 hours on each of the two study days ]
  • Heart rate at every time point of the study [ Time Frame: every hour during 12 hours on each of the two study days ]
  • Symptoms of hyponatremia assessed by visual analogue scale (VAS) at every time point of the study [ Time Frame: every hour during 12 hours on each of the two study days ]
  • Urinary sodium level [ Time Frame: every 2 hours for twelve hours on each of the two study days ]


Original Secondary Outcome:

  • Serum sodium concentration at every time point of the study [ Time Frame: every hour for twelve hours on each of the two study days ]
  • Amount of urinary excretion [ Time Frame: every hour for twelve hours on each of the two study days ]
  • Serum osmolality at every time point of the study [ Time Frame: every hour for twelve hours on each of the two study days ]
  • Serum glucose at every time point of the study [ Time Frame: every hour for twelve hours on each of the two study days ]
  • Urinary osmolality at every time point of the study [ Time Frame: every hour for twelve hours on each of the two study days ]
  • Urinary glucose at every time point of the study [ Time Frame: every hour for twelve hours on each of the two study days ]
  • Serum electrolytes before induction of siad, at baseline and time point 7 [ Time Frame: 9 hours on each of the two study days ]
  • Urinary electrolytes before induction of siad, at baseline and time point 7 [ Time Frame: 9 hours on each of the two study days ]
  • Plasma level of Copeptin before induction of siad, at baseline and time point 7 [ Time Frame: 9 hours on each of the two study days ]
  • Plasma level of Aldosterone before induction of siad, at baseline and time point 7 [ Time Frame: 9 hours on each of the two study days ]
  • Plasma level of Renin before induction of siad, at baseline and time point 7 [ Time Frame: 9 hours on each of the two study days ]
  • Plasma Level of atrial natriuretic peptide (ANP) before induction of siad, at baseline and time point 7 [ Time Frame: 9 hours on each of the two study days ]
  • Plasma levels of brain natriuretic peptide (BNP) before induction of siad, at baseline and time point 7 [ Time Frame: 9 hours on each of the two study days ]
  • Body weight at every time point of the study [ Time Frame: every hour during 12 hours on each of the two study days ]
  • Blood pressure at every time point of the study [ Time Frame: every hour during 12 hours on each of the two study days ]
  • Heart rate at every time point of the study [ Time Frame: every hour during 12 hours on each of the two study days ]
  • Symptoms of hyponatremia assessed by visual analogue scale (VAS) at every time point of the study [ Time Frame: every hour during 12 hours on each of the two study days ]


Information By: University Hospital, Basel, Switzerland

Dates:
Date Received: March 24, 2016
Date Started: March 2016
Date Completion:
Last Updated: August 9, 2016
Last Verified: August 2016