Inappropriate ADH SyndromePhase 2/3DIVENCT02729766
Effects of Empagliflozin an SGLT2-Inhibitor on Healthy Volunteers With Induced Hypotonic Hyponatremia - the DIVE Study
A Phase 2/3 study testing Induced hypotonic hyponatremia - SIAD model and Empagliflozin 25mg Tbl in people with Inappropriate ADH Syndrome, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Inappropriate ADH Syndrome
- What is being tested?
- Induced hypotonic hyponatremia - SIAD model and Empagliflozin 25mg Tbl
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteSwitzerland
- Study dates
- Mar 2016to Aug 2016
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Informed consent as documented by signature
- Age 18 to 65 years
- serum sodium level 135-145mmol/l
- clinically euvolemic status
Who cannot join
- 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
Show all 15Show fewer
- 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 locations and contacts
1 site in 1 country.
Switzerland1 site
Department Endocrinology University Hospital Basel
Basel, Basel, 4031
About this study
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
- Being tested
- Induced hypotonic hyponatremia - SIAD model, Empagliflozin 25mg Tbl, Placebo P-Tablet
- Keywords
- Hyponatremia, SGLT2 inhibitor
- Medical subject headings
- Inappropriate ADH Syndrome, Hyponatremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Induced hypotonic hyponatremia - SIAD modelOther
Also called Induced hypotonic hyponatremia
Empagliflozin 25mg TblDrug
Placebo P-TabletDrug
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Induced hypotonic hyponatremia - SIAD model; Drug: Placebo P-Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: every hour for twelve hours on each of the two study days
Amount of urinary excretion
Measured: every 2 hours for twelve hours on each of the two study days
Serum osmolality at every time point of the study
Measured: every hour for twelve hours on each of the two study days
Serum glucose at every time point of the study
Measured: every hour for twelve hours on each of the two study days
Urinary osmolality
Measured: every two hours for twelve hours on each of the two study days
Urinary glucose
Measured: every 2 hours for twelve hours on each of the two study days
Serum electrolytes at time point -1, 0, 2 and 8
Measured: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Urinary electrolytes at time point -1, 0, 2 and 8
Measured: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Plasma level of Copeptin at time point -1, 0, 2 and 8
Measured: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Plasma level of Aldosterone at time point -1, 0, 2 and 8
Measured: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Plasma level of Renin at time point -1, 0, 2 and 8
Measured: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Plasma Level of atrial natriuretic peptide (ANP) at time point -1, 0, 2 and 8
Measured: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Plasma levels of brain natriuretic peptide (BNP) at time point -1, 0, 2 and 8
Measured: 1 hour before induction of siad, at baseline, 2 hours and 8 hours after administration of study medication on each study day
Body weight at every time point of the study
Measured: every hour during 12 hours on each of the two study days
Blood pressure at every time point of the study
Measured: every hour during 12 hours on each of the two study days
Heart rate at every time point of the study
Measured: every hour during 12 hours on each of the two study days
Symptoms of hyponatremia assessed by visual analogue scale (VAS) at every time point of the study
Measured: every hour during 12 hours on each of the two study days
Urinary sodium level
Measured: every 2 hours for twelve hours on each of the two study days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2016 (estimated)
- Study startMar 2016
- Primary completionJul 2016
- Study completionAug 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Inappropriate ADH SyndromeStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mirjam Christ-Crain, Prof., Principal investigator, Deputy chief division endocrinology university hospital basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02729766
- Sponsor's protocol ID
- 2015-00024
- Other IDs
- 2015
- Acronym
- DIVE
- Status last verified
- Aug 2016
- First submitted
- 24 Mar 2016
- Last updated
- 10 Aug 2016
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Aug 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Empagliflozin an SGLT2-Inhibitor on Healthy Volunteers With Induced Hypotonic Hyponatremia - the DIVE Study
- ClinicalTrials.gov ID
- NCT02729766
- Acronym / sponsor ID
- DIVE / 2015-00024
- Conditions
- Inappropriate ADH Syndrome
- Keywords
- Hyponatremia, SGLT2 inhibitor
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- Mar 2016
- Primary completion
- Jul 2016 (actual)
- Study completion
- Aug 2016 (actual)
- First posted
- 6 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Empagliflozin 25mg Tbl | Active comparator | Other: Induced hypotonic hyponatremia - SIAD model, Drug: Empagliflozin 25mg TblInduced 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. |
| Placebo P-Tablet | Placebo comparator | Other: Induced hypotonic hyponatremia - SIAD model, Drug: Placebo P-TabletInduced 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Informed consent as documented by signature
- Age 18 to 65 years
- serum sodium level 135-145mmol/l
- clinically euvolemic status
Key exclusion criteria (15 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Induced hypotonic hyponatremia - SIAD modelAlso: Induced hypotonic hyponatremia | Other | Empagliflozin 25mg Tbl, Placebo P-Tablet |
| Empagliflozin 25mg Tbl | Drug | Empagliflozin 25mg Tbl |
| Placebo P-Tablet | Drug | Placebo P-Tablet |
Primary outcome
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
18 secondary outcomes
Serum sodium concentration at every time point of the study
Time frame: every hour for twelve hours on each of the two study days
Amount of urinary excretion
Time frame: every 2 hours for twelve hours on each of the two study days
Serum osmolality at every time point of the study
Time frame: every hour for twelve hours on each of the two study days
Serum glucose at every time point of the study
Time frame: every hour for twelve hours on each of the two study days
Urinary osmolality
Time frame: every two hours for twelve hours on each of the two study days
Urinary glucose
Time frame: every 2 hours for twelve hours on each of the two study days
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
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
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
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
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
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
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
Body weight at every time point of the study
Time frame: every hour during 12 hours on each of the two study days
Blood pressure at every time point of the study
Time frame: every hour during 12 hours on each of the two study days
Heart rate at every time point of the study
Time frame: every hour during 12 hours on each of the two study days
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
Urinary sodium level
Time frame: every 2 hours for twelve hours on each of the two study days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Aug 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mirjam Christ-Crain, Prof. principal investigator
Deputy chief division endocrinology university hospital basel
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Induced hypotonic hyponatremia - SIAD model and Empagliflozin 25mg Tbl in people with Inappropriate ADH Syndrome, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Aug 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Aug 2016.