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

Primary Purpose

Inappropriate ADH Syndrome

Status
Completed
Phase
Phase 2
Locations
Switzerland
Study Type
Interventional
Intervention
Induced hypotonic hyponatremia - SIAD model
Empagliflozin 25mg Tbl
Placebo P-Tablet
Sponsored by
University Hospital, Basel, Switzerland
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Inappropriate ADH Syndrome focused on measuring Hyponatremia, SGLT2 inhibitor

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesAccepts 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

Sites / Locations

  • Department Endocrinology University Hospital Basel

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Empagliflozin 25mg Tbl

Placebo P-Tablet

Arm 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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Serum sodium concentration at every time point of the study
Amount of urinary excretion
Serum osmolality at every time point of the study
Serum glucose at every time point of the study
Urinary osmolality
Urinary glucose
Serum electrolytes at time point -1, 0, 2 and 8
Urinary electrolytes at time point -1, 0, 2 and 8
Plasma level of Copeptin at time point -1, 0, 2 and 8
Plasma level of Aldosterone at time point -1, 0, 2 and 8
Plasma level of Renin at time point -1, 0, 2 and 8
Plasma Level of atrial natriuretic peptide (ANP) at time point -1, 0, 2 and 8
Plasma levels of brain natriuretic peptide (BNP) at time point -1, 0, 2 and 8
Body weight at every time point of the study
Blood pressure at every time point of the study
Heart rate at every time point of the study
Symptoms of hyponatremia assessed by visual analogue scale (VAS) at every time point of the study
Urinary sodium level

Full Information

First Posted
March 24, 2016
Last Updated
August 9, 2016
Sponsor
University Hospital, Basel, Switzerland
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1. Study Identification

Unique Protocol Identification Number
NCT02729766
Brief Title
Effects of Empagliflozin an SGLT2-Inhibitor on Healthy Volunteers With Induced Hypotonic Hyponatremia - the DIVE Study
Acronym
DIVE
Official Title
Effects of Empagliflozin an SGLT2-Inhibitor on Healthy Volunteers With Induced Hypotonic Hyponatremia - the DIVE Study
Study Type
Interventional

2. Study Status

Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
March 2016 (undefined)
Primary Completion Date
July 2016 (Actual)
Study Completion Date
August 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Basel, Switzerland

4. Oversight

Data Monitoring Committee
No

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inappropriate ADH Syndrome
Keywords
Hyponatremia, SGLT2 inhibitor

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Empagliflozin 25mg Tbl
Arm Type
Active Comparator
Arm 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.
Arm Title
Placebo P-Tablet
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Other
Intervention Name(s)
Induced hypotonic hyponatremia - SIAD model
Other Intervention Name(s)
Induced hypotonic hyponatremia
Intervention Type
Drug
Intervention Name(s)
Empagliflozin 25mg Tbl
Intervention Type
Drug
Intervention Name(s)
Placebo P-Tablet
Primary Outcome Measure Information:
Title
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.
Time Frame
concentration measured every hour within 8 hours after drug administration on both study days
Secondary Outcome Measure Information:
Title
Serum sodium concentration at every time point of the study
Time Frame
every hour for twelve hours on each of the two study days
Title
Amount of urinary excretion
Time Frame
every 2 hours for twelve hours on each of the two study days
Title
Serum osmolality at every time point of the study
Time Frame
every hour for twelve hours on each of the two study days
Title
Serum glucose at every time point of the study
Time Frame
every hour for twelve hours on each of the two study days
Title
Urinary osmolality
Time Frame
every two hours for twelve hours on each of the two study days
Title
Urinary glucose
Time Frame
every 2 hours for twelve hours on each of the two study days
Title
Serum electrolytes at time point -1, 0, 2 and 8
Time Frame
1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Title
Urinary electrolytes at time point -1, 0, 2 and 8
Time Frame
1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Title
Plasma level of Copeptin at time point -1, 0, 2 and 8
Time Frame
1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Title
Plasma level of Aldosterone at time point -1, 0, 2 and 8
Time Frame
1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Title
Plasma level of Renin at time point -1, 0, 2 and 8
Time Frame
1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Title
Plasma Level of atrial natriuretic peptide (ANP) at time point -1, 0, 2 and 8
Time Frame
1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Title
Plasma levels of brain natriuretic peptide (BNP) at time point -1, 0, 2 and 8
Time Frame
1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Title
Body weight at every time point of the study
Time Frame
every hour during 12 hours on each of the two study days
Title
Blood pressure at every time point of the study
Time Frame
every hour during 12 hours on each of the two study days
Title
Heart rate at every time point of the study
Time Frame
every hour during 12 hours on each of the two study days
Title
Symptoms of hyponatremia assessed by visual analogue scale (VAS) at every time point of the study
Time Frame
every hour during 12 hours on each of the two study days
Title
Urinary sodium level
Time Frame
every 2 hours for twelve hours on each of the two study days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mirjam Christ-Crain, Prof.
Organizational Affiliation
Deputy chief division endocrinology university hospital basel
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department Endocrinology University Hospital Basel
City
Basel
ZIP/Postal Code
4031
Country
Switzerland

12. IPD Sharing Statement

Learn more about this trial

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

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