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

University Hospital Basel

Status and phase: Completed; Phase 3; Phase 2

Conditions: Inappropriate ADH Syndrome

Treatments: Drug: Empagliflozin 25mg Tbl; Drug: Placebo P-Tablet; Other: Induced hypotonic hyponatremia - SIAD model

Study type: Interventional

Funder types: Other

Identifiers

NCT02729766

2015-00024

Details and patient eligibility

About

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.

Enrollment: 15 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

---

15 participants in 2 patient groups, including a placebo group

Empagliflozin 25mg Tbl

Active Comparator group

Description:

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.

Treatment:

Other: Induced hypotonic hyponatremia - SIAD model

Drug: Empagliflozin 25mg Tbl

Placebo P-Tablet

Placebo Comparator group

Description:

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.

Treatment:

Other: Induced hypotonic hyponatremia - SIAD model

Drug: Placebo P-Tablet