COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02729766
Recruitment Status : Completed
First Posted : April 6, 2016
Last Update Posted : August 10, 2016
Sponsor:
Information provided by (Responsible Party):
University Hospital, Basel, Switzerland

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : March 2016
Actual Primary Completion Date : July 2016
Actual Study Completion Date : August 2016

Resource links provided by the National Library of Medicine


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 Name: 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 Name: Induced hypotonic hyponatremia

Drug: Placebo P-Tablet



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. [ Time Frame: 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 [ Time Frame: every hour for twelve hours on each of the two study days ]
  2. Amount of urinary excretion [ Time Frame: every 2 hours for twelve hours on each of the two study days ]
  3. Serum osmolality at every time point of the study [ Time Frame: every hour for twelve hours on each of the two study days ]
  4. Serum glucose at every time point of the study [ Time Frame: every hour for twelve hours on each of the two study days ]
  5. Urinary osmolality [ Time Frame: every two hours for twelve hours on each of the two study days ]
  6. Urinary glucose [ Time Frame: every 2 hours for twelve hours on each of the two study days ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. Body weight at every time point of the study [ Time Frame: every hour during 12 hours on each of the two study days ]
  15. Blood pressure at every time point of the study [ Time Frame: every hour during 12 hours on each of the two study days ]
  16. Heart rate at every time point of the study [ Time Frame: 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 [ Time Frame: every hour during 12 hours on each of the two study days ]
  18. Urinary sodium level [ Time Frame: every 2 hours for twelve hours on each of the two study days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02729766


Locations
Layout table for location information
Switzerland
Department Endocrinology University Hospital Basel
Basel, Switzerland, 4031
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Layout table for investigator information
Principal Investigator: Mirjam Christ-Crain, Prof. Deputy chief division endocrinology university hospital basel
Layout table for additonal information
Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT02729766    
Other Study ID Numbers: 2015-00024
First Posted: April 6, 2016    Key Record Dates
Last Update Posted: August 10, 2016
Last Verified: August 2016
Keywords provided by University Hospital, Basel, Switzerland:
Hyponatremia
SGLT2 inhibitor
Additional relevant MeSH terms:
Layout table for MeSH terms
Inappropriate ADH Syndrome
Hyponatremia
Water-Electrolyte Imbalance
Metabolic Diseases
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Empagliflozin
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs