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

NCT ID: NCT02729766

Last Updated: 2016-08-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2016-08-31

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.

Conditions

Inappropriate ADH Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Induced hypotonic hyponatremia - SIAD model

Intervention Type: OTHER

Empagliflozin 25mg Tbl

Intervention Type: DRUG

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.

Group Type: PLACEBO_COMPARATOR

Induced hypotonic hyponatremia - SIAD model

Intervention Type: OTHER

Placebo P-Tablet

Intervention Type: DRUG

Interventions

Induced hypotonic hyponatremia - SIAD model

Intervention Type: OTHER

Empagliflozin 25mg Tbl

Intervention Type: DRUG

Placebo P-Tablet

Intervention Type: DRUG

Other Intervention Names

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University Hospital, Basel, Switzerland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mirjam Christ-Crain, Prof.

Role: PRINCIPAL_INVESTIGATOR

Deputy chief division endocrinology university hospital basel

Locations

Department Endocrinology University Hospital Basel

Basel, Basel, Switzerland

Countries

Switzerland

Other Identifiers

2015-00024

Identifier Type: -

Identifier Source: org_study_id