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

• Sponsor: University Hospital, Basel, Switzerland (Other)
• Overall Status: Completed
• CT.gov ID: NCT02729766
• Collaborator: (none)
• Enrollment: 15
• Location: 1
• Arms: 2
• Duration (Months): 5
• Patients Per Site Per Month: 3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Inappropriate ADH Syndrome	Other: Induced hypotonic hyponatremia - SIAD model; Drug: Empagliflozin 25mg Tbl; Drug: Placebo P-Tablet	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 15 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Empagliflozin an SGLT2-Inhibitor on Healthy Volunteers With Induced Hypotonic Hyponatremia - the DIVE Study
• Study Start Date: Mar 1, 2016
• Actual Primary Completion Date: Jul 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: 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.	Other: Induced hypotonic hyponatremia - SIAD model; Other Names: Induced hypotonic hyponatremia ; Drug: Empagliflozin 25mg Tbl
Placebo Comparator: 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.	Other: Induced hypotonic hyponatremia - SIAD model; Other Names: Induced hypotonic hyponatremia ; Drug: Placebo P-Tablet

Outcome Measures

Primary Outcome Measures

1. 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]

Secondary Outcome Measures

1. Serum sodium concentration at every time point of the study [every hour for twelve hours on each of the two study days]

2. Amount of urinary excretion [every 2 hours for twelve hours on each of the two study days]

3. Serum osmolality at every time point of the study [every hour for twelve hours on each of the two study days]

4. Serum glucose at every time point of the study [every hour for twelve hours on each of the two study days]

5. Urinary osmolality [every two hours for twelve hours on each of the two study days]

6. Urinary glucose [every 2 hours for twelve hours on each of the two study days]

7. 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]

8. 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]

9. 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]

10. 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]

11. 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]

12. 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]

13. 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]

14. Body weight at every time point of the study [every hour during 12 hours on each of the two study days]

15. Blood pressure at every time point of the study [every hour during 12 hours on each of the two study days]

16. Heart rate at every time point of the study [every hour during 12 hours on each of the two study days]

17. 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]

18. Urinary sodium level [every 2 hours for twelve hours on each of the two study days]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department Endocrinology University Hospital Basel	Basel		Switzerland	4031

Sponsors and Collaborators

• University Hospital, Basel, Switzerland

Investigators

• Principal Investigator: Mirjam Christ-Crain, Prof., Deputy chief division endocrinology university hospital basel

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University Hospital, Basel, Switzerland
• ClinicalTrials.gov Identifier: NCT02729766
• Other Study ID Numbers: 2015-00024
• First Posted: Apr 6, 2016
• Last Update Posted: Aug 10, 2016
• Last Verified: Aug 1, 2016

• Keywords provided by University Hospital, Basel, Switzerland: Hyponatremia; SGLT2 inhibitor
• Additional relevant MeSH terms: Inappropriate ADH Syndrome; Hyponatremia; Empagliflozin

Study Results

No Results Posted as of Aug 10, 2016