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

NCT02729766 | Completed Phase 2

• 1 other identifier: 2015-00024
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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

Keywords

Hyponatremia; SGLT2 inhibitor

Outcome Measures

Primary Outcomes (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 Outcomes (18)

• Serum sodium concentration at every time point of the study

  every hour for twelve hours on each of the two study days

• Amount of urinary excretion

  every 2 hours for twelve hours on each of the two study days

• Serum osmolality at every time point of the study

  every hour for twelve hours on each of the two study days

• Serum glucose at every time point of the study

  every hour for twelve hours on each of the two study days

• Urinary osmolality

  every two hours for twelve hours on each of the two study days

Study Arms (2)

Empagliflozin 25mg Tbl

ACTIVE COMPARATOR

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; Drug: Empagliflozin 25mg Tbl

Placebo P-Tablet

PLACEBO COMPARATOR

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; Drug: Placebo P-Tablet

Interventions

Induced hypotonic hyponatremia - SIAD model OTHER

Also known as: Induced hypotonic hyponatremia

Empagliflozin 25mg Tbl; Placebo P-Tablet

Empagliflozin 25mg Tbl DRUG

Empagliflozin 25mg Tbl

Placebo P-Tablet DRUG

Placebo P-Tablet

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed consent as documented by signature
• Age 18 to 65 years
• serum sodium level 135-145mmol/l
• clinically euvolemic status

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

Study Sites (1)

Department Endocrinology University Hospital Basel

Basel, Basel, 4031, Switzerland

Location

MeSH Terms

Conditions

Inappropriate ADH Syndrome; Hyponatremia

Interventions

empagliflozin; Tablets

Condition Hierarchy (Ancestors)

Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Water-Electrolyte Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Dosage Forms; Pharmaceutical Preparations

Study Officials

• Mirjam Christ-Crain, Prof.

  Deputy chief division endocrinology university hospital basel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 24, 2016
• First Posted: April 6, 2016
• Study Start: March 1, 2016
• Primary Completion: July 1, 2016
• Study Completion: August 1, 2016
• Last Updated: August 10, 2016

Record last verified: 2016-08

Locations

CH (1)