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

Inappropriate ADH Syndrome Clinical Trial

— DIVE  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02729766
• Other study ID #: 2015-00024
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: March 24, 2016
• Last updated: August 9, 2016
• Start date: March 2016
• Est. completion date: August 2016

Study information

• Verified date: August 2016
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Swissmedic
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: August 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hyponatremia
• Inappropriate ADH Syndrome

Intervention

Other:
• Induced hypotonic hyponatremia - SIAD model

Drug:
• Empagliflozin 25mg Tbl

• Placebo P-Tablet

Locations

Country	Name	City	State
Switzerland	Department Endocrinology University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.		concentration measured every hour within 8 hours after drug administration on both study days	No
Secondary	Serum sodium concentration at every time point of the study		every hour for twelve hours on each of the two study days	No
Secondary	Amount of urinary excretion		every 2 hours for twelve hours on each of the two study days	No
Secondary	Serum osmolality at every time point of the study		every hour for twelve hours on each of the two study days	No
Secondary	Serum glucose at every time point of the study		every hour for twelve hours on each of the two study days	No
Secondary	Urinary osmolality		every two hours for twelve hours on each of the two study days	No
Secondary	Urinary glucose		every 2 hours for twelve hours on each of the two study days	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Body weight at every time point of the study		every hour during 12 hours on each of the two study days	No
Secondary	Blood pressure at every time point of the study		every hour during 12 hours on each of the two study days	No
Secondary	Heart rate at every time point of the study		every hour during 12 hours on each of the two study days	No
Secondary	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	No
Secondary	Urinary sodium level		every 2 hours for twelve hours on each of the two study days	No