SIAD - Syndrome of Inappropriate AntidiuresisPhase 2/3SANDxNCT03202667
Effects of the SGLT2-inhibitor Empagliflozin on Patients With Chronic SIADH - the SANDx Study
A Phase 2/3 study testing Empagliflozin 25mg in people with SIAD - Syndrome of Inappropriate Antidiuresis and Hyponatremia, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
Syndrome of inappropriate antidiuresis (SIADH) is characterized by an imbalance of antidiuretic vasopressin (AVP) secretion. The impaired AVP regulation leads to water retention and secondary natriuresis and is a common cause for hyponatremia. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- SIAD - Syndrome of Inappropriate Antidiuresis, Hyponatremia
- What is being tested?
- Empagliflozin 25mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteSwitzerland
- Study dates
- 15 Dec 2017to 6 Dec 2021
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients (age ≥ 18 years) with hyponatremia (<133mmol/l) due to chronic (>72h) SIADH defined as
- serum osmolality <275mosm/kg
- urine osmolality >100mosm/kg
- urine sodium >30mmol/l
Who cannot join
- acute (<72h) or transient hyponatremia
- severe symptomatic hyponatremia in need of hospital treatment
- diabetes mellitus type 1
- uncontrolled hypothyroidism
- uncontrolled adrenal insufficiency
- renal impairment (GFR <45ml/min)
Show all 12Show fewer
- cardiac failure
- symptomatic liver disease / severe hepatic impairment (ALAT / aspartate transaminase (ASAT) > 3x upper limit)
- treatment with SGLT 2 inhibitors, lithium chloride, urea or glitazone
- severe immunosuppression
- pregnancy or breastfeeding
- palliative situation (end of life care)
Trial locations and contacts
1 site in 1 country.
About this study
Syndrome of inappropriate antidiuresis (SIADH) is characterized by an imbalance of antidiuretic vasopressin (AVP) secretion. The impaired AVP regulation leads to water retention and secondary natriuresis and is a common cause for hyponatremia.
Especially chronic (>72h) SIADH is difficult to treat as standard therapeutic options (water restriction, urea, salt tablets) often do not succeed in correction of hyponatremia, making additional therapy necessary.
Read more
Empagliflozin is a sodium glucose co-transporter 2 (SGLT2)-inhibitor, which is a well-tolerated treatment option for type 2 diabetes mellitus. The inhibition of SGLT2 in the proximal tubule leads to renal excretion of glucose with subsequent osmotic diuresis. This mechanism could result in a therapeutic effect in patients with chronic SIADH, as it resembles the aquaretic effect of urea.
The aim of this study is to evaluate whether empagliflozin has an effect on the serum sodium levels of patients with chronic SIADH.
- Being tested
- Empagliflozin 25mg, Placebo
- Keywords
- SGLT2-inhibitor, Treatment
- 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.
Empagliflozin 25mgDrug
Treatment with empagliflozin 25mg once daily for 28 days
PlaceboDrug
Treatment with Placebo oral tablet once daily for 28 days
| Study group | Role | What they receive |
|---|---|---|
| Empagliflozin | Active comparator | Treatment with empagliflozin 25mg tablets once daily for 28 days Receives: Drug: Empagliflozin 25mg |
| Placebo | Placebo comparator | Treatment with Placebo tablets once daily for 28 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Serum Sodium concentration
Difference in serum sodium concentration in mmol/l after 28 days of treatment
Measured: 28 days
Secondary outcomes (72)
Change in Serum sodium concentration
Serum sodium concentration 1, 2 and 3 weeks of treatment
Measured: 21 days
Change in Serum electrolytes
Serum electrolytes after 1, 2, 3 and 4 weeks of treatment
Measured: 28 days
Urinary electrolytes
Urinary electrolytes after 1 week of treatment
Measured: 7 days
Urinary electrolytes
Urinary electrolytes after 2 weeks of treatment
Measured: 14 days
Urinary electrolytes
Urinary electrolytes after 3 weeks of treatment
Measured: 21 days
Urinary electrolytes
Urinary electrolytes after 4 weeks of treatment
Measured: 28 days
Serum osmolality
Serum osmolality after 1 week of treatment
Measured: 7 days
Serum osmolality
Serum osmolality after 2 weeks of treatment
Measured: 14 days
Serum osmolality
Serum osmolality after 3 weeks of treatment
Measured: 21 days
Serum osmolality
Serum osmolality after 4 weeks of treatment
Measured: 28 days
Urinary osmolality
Urinary osmolality after 1 week of treatment
Measured: 7 days
Urinary osmolality
Urinary osmolality after 2 weeks of treatment
Measured: 14 days
Urinary osmolality
Urinary osmolality after3 weeks of treatment
Measured: 21 days
Urinary osmolality
Urinary osmolality after 4 weeks of treatment
Measured: 28 days
Serum glucose
Serum glucose after 1 week of treatment
Measured: 7 days
Serum glucose
Serum glucose after 2 weeks of treatment
Measured: 14 days
Serum glucose
Serum glucose after 3 weeks of treatment
Measured: 21 days
Serum glucose
Serum glucose after 4 weeks of treatment
Measured: 28 days
Urinary glucose
Urinary glucose after 1 week of treatment
Measured: 7 days
Urinary glucose
Urinary glucose after 2 weeks of treatment
Measured: 14 days
Urinary glucose
Urinary glucose after 3 weeks of treatment
Measured: 21 days
Urinary glucose
Urinary glucose after 4 weeks of treatment
Measured: 28 days
Copeptin
Plasma copeptin after 1 week of treatment
Measured: 7 days
Copeptin
Plasma copeptin after 2 weeks of treatment
Measured: 14 days
Copeptin
Plasma copeptin after3 weeks of treatment
Measured: 21 days
Copeptin
Plasma copeptin after 4 weeks of treatment
Measured: 28 days
Aldosterone
Plasma aldosterone after 1 week of treatment
Measured: 7 days
Aldosterone
Plasma aldosterone after 2 weeks of treatment
Measured: 14 days
Aldosterone
Plasma aldosterone after 3 weeks of treatment
Measured: 21 days
Aldosterone
Plasma aldosterone after 4 weeks of treatment
Measured: 28 days
Renin
Plasma renin after 1 week of treatment
Measured: 7 days
Renin
Plasma renin after 2 weeks of treatment
Measured: 14 days
Renin
Plasma renin after 3 weeks of treatment
Measured: 21 days
Renin
Plasma renin after 4 weeks of treatment
Measured: 28 days
MR-proANP
Plasma MR-proANP after 1 week of treatment
Measured: 7 days
MR-proANP
Plasma MR-proANP after 2 weeks of treatment
Measured: 14 days
MR-proANP
Plasma MR-proANP after 3 weeks of treatment
Measured: 21 days
MR-proANP
Plasma MR-proANP after 4 weeks of treatment
Measured: 28 days
N terminal (NT)-proBNP
Plasma NT-proBNP after 1 week of treatment
Measured: 7 days
NT-proBNP
Plasma NT-proBNP after 2 weeks of treatment
Measured: 14 days
NT-proBNP
Plasma NT-proBNP after 3 weeks of treatment
Measured: 21 days
NT-proBNP
Plasma NT-proBNP after 4 weeks of treatment
Measured: 28 days
P1NP
Plasma P1NP after 1 week of treatment
Measured: 7 days
P1NP
Plasma P1NP after 2 weeks of treatment
Measured: 14 days
P1NP
Plasma P1NP after 3 weeks of treatment
Measured: 21 days
P1NP
Plasma P1NP after 4 weeks of treatment
Measured: 28 days
CTx
Plasma CTx after 1 week of treatment
Measured: 7 days
CTx
Plasma CTx after 2 weeks of treatment
Measured: 14 days
CTx
Plasma CTx after 3 weeks of treatment
Measured: 21 days
CTx
Plasma CTx after 4 weeks of treatment
Measured: 28 days
Osteocalcin
Plasma Osteocalcin after 1 week of treatment
Measured: 7 days
Osteocalcin
Plasma Osteocalcin after 2 weeks of treatment
Measured: 14 days
Osteocalcin
Plasma Osteocalcin after 3 weeks of treatment
Measured: 21 days
Osteocalcin
Plasma Osteocalcin after 4 weeks of treatment
Measured: 28 days
General well being (assessed by VAS)
General well being after 1, 2, 3 and 4 weeks of treatment
Measured: 28 days
Headache (assessed by VAS)
Headache after 1, 2, 3 and 4 weeks of treatment
Measured: 28 days
Vertigo (assessed by VAS)
vertigo after 1, 2, 3 and 4 weeks of treatment
Measured: 28 days
Nausea (assessed by VAS)
Nausea after 1, 2, 3 and 4 weeks of treatment
Measured: 28 days
Malaise (assessed by VAS)
Malaise after 1, 2, 3 and 4 weeks of treatment
Measured: 28 days
Body weight (kg)
Body weight after 1, 2, 3 and 4 weeks of treatment
Measured: 28 days
Blood pressure (mmHg)
Blood pressure after 1, 2, 3 and 4 weeks of treatment
Measured: 28 days
Heart rate (bpm)
Heart rate after 1, 2, 3 and 4 weeks of treatment
Measured: 28 days
Neurocognitive function (assessed by MOCA)
change in Neurocognitive function (baseline versus after 4 weeks of Treatment)
Measured: 28 days
Muscle strength (measured by grip strength test)
Change in Muscle strength (baseline vs after 4 weeks of Treatment)
Measured: 28 days
Gait Dynamics (measured by gait Analysis)
Gait dynamics baseline vs after 4 weeks of treatment
Measured: 28 days
Hemodynamic Parameters (measured by thoracic electrical bioimpedance)
Hemodynamic parameters baseline vs after 4 weeks of treatment
Measured: 28 days
Body fluid volume (measured by bioimpedance spectroscopy)
Body fluid volume baseline vs after 4 weeks of treatment
Measured: 28 days
Amount of Fluid intake in ml
Fluid intake after 1, 2, 3 and 4 weeks of treatment
Measured: 28 days
Number of Falls
Rate of falls during observation phase
Measured: 30 days
number of Fractures
Rate of fractures during observation phase
Measured: 30 days
number of Hospital admissions
Rate of Hospital admissions during observation phase
Measured: 30 days
Hyponatremia recurrence
Rate of hyponatremia recurrence during 30day follow up
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jun 2017
- Study start15 Dec 2017
- Primary completion26 Aug 2021
- Study completion6 Dec 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for SIAD - Syndrome of Inappropriate AntidiuresisStudies 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
- 17 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. Dr. MD, Study director, University Hopsital Basel
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03202667
- Sponsor's protocol ID
- 2017-00701
- Other IDs
- 2017
- Acronym
- SANDx
- Status last verified
- Dec 2021
- First submitted
- 27 Jun 2017
- Last updated
- 13 Dec 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kustos-Toth E, Beck J, Seeger L, Monnerat S, Bathelt C, Refardt J, Christ-Crain M. Hyponatremia correction is associated with increased brain-derived neurotrophic factor levels: A pilot secondary analysis of a randomized, double-blind, placebo-controlled, crossover trial. J Neuroendocrinol. 2026 Aug;38(8):e70238. doi: 10.1111/jne.70238.
PubMed 42522233Monnerat S, Refardt J, Potasso L, Meier C, Christ-Crain M. An Increase in Plasma Sodium Levels Is Associated With an Increase in Osteoblast Function in Chronic SIAD. J Clin Endocrinol Metab. 2023 Sep 18;108(10):e1027-e1033. doi: 10.1210/clinem/dgad238.
PubMed 37098131Refardt J, Imber C, Nobbenhuis R, Sailer CO, Haslbauer A, Monnerat S, Bathelt C, Vogt DR, Berres M, Winzeler B, Bridenbaugh SA, Christ-Crain M. Treatment Effect of the SGLT2 Inhibitor Empagliflozin on Chronic Syndrome of Inappropriate Antidiuresis: Results of a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial. J Am Soc Nephrol. 2023 Feb 1;34(2):322-332. doi: 10.1681/ASN.2022050623. Epub 2022 Nov 17.
PubMed 36396331
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of the SGLT2-inhibitor Empagliflozin on Patients With Chronic SIADH - the SANDx Study
- ClinicalTrials.gov ID
- NCT03202667
- Acronym / sponsor ID
- SANDx / 2017-00701
- Keywords
- SGLT2-inhibitor, Treatment
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 15 Dec 2017 (actual)
- Primary completion
- 26 Aug 2021 (actual)
- Study completion
- 6 Dec 2021 (actual)
- First posted
- 28 Jun 2017 (actual)
- 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.
Syndrome of inappropriate antidiuresis (SIADH) is characterized by an imbalance of antidiuretic vasopressin (AVP) secretion. The impaired AVP regulation leads to water retention and secondary natriuresis and is a common cause for hyponatremia.
Especially chronic (>72h) SIADH is difficult to treat as standard therapeutic options (water restriction, urea, salt tablets) often do not succeed in correction of hyponatremia, making additional therapy necessary.
Empagliflozin is a sodium glucose co-transporter 2 (SGLT2)-inhibitor, which is a well-tolerated treatment option for type 2 diabetes mellitus. The inhibition of SGLT2 in the proximal tubule leads to renal excretion of glucose with subsequent osmotic diuresis. This mechanism could result in a therapeutic effect in patients with chronic SIADH, as it resembles the aquaretic effect of urea.
The aim of this study is to evaluate whether empagliflozin has an effect on the serum sodium levels of patients with chronic SIADH.
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 | Active comparator | Drug: Empagliflozin 25mgTreatment with empagliflozin 25mg tablets once daily for 28 days |
| Placebo | Placebo comparator | Drug: PlaceboTreatment with Placebo tablets once daily for 28 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult patients (age ≥ 18 years) with hyponatremia (<133mmol/l) due to chronic (>72h) SIADH defined as
- serum osmolality <275mosm/kg
- urine osmolality >100mosm/kg
- urine sodium >30mmol/l
Key exclusion criteria (12 listed)
- acute (<72h) or transient hyponatremia
- severe symptomatic hyponatremia in need of hospital treatment
- diabetes mellitus type 1
- uncontrolled hypothyroidism
- uncontrolled adrenal insufficiency
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 |
|---|---|---|
| Empagliflozin 25mgTreatment with empagliflozin 25mg once daily for 28 days | Drug | Empagliflozin |
| PlaceboTreatment with Placebo oral tablet once daily for 28 days | Drug | Placebo |
Primary outcome
Change in Serum Sodium concentration
Time frame: 28 days
Difference in serum sodium concentration in mmol/l after 28 days of treatment
72 secondary outcomes
Change in Serum sodium concentration
Time frame: 21 days
Change in Serum electrolytes
Time frame: 28 days
Urinary electrolytes
Time frame: 7 days
Urinary electrolytes
Time frame: 14 days
Urinary electrolytes
Time frame: 21 days
Urinary electrolytes
Time frame: 28 days
Serum osmolality
Time frame: 7 days
Serum osmolality
Time frame: 14 days
Serum osmolality
Time frame: 21 days
Serum osmolality
Time frame: 28 days
Urinary osmolality
Time frame: 7 days
Urinary osmolality
Time frame: 14 days
Urinary osmolality
Time frame: 21 days
Urinary osmolality
Time frame: 28 days
Serum glucose
Time frame: 7 days
Serum glucose
Time frame: 14 days
Serum glucose
Time frame: 21 days
Serum glucose
Time frame: 28 days
Urinary glucose
Time frame: 7 days
Urinary glucose
Time frame: 14 days
Urinary glucose
Time frame: 21 days
Urinary glucose
Time frame: 28 days
Copeptin
Time frame: 7 days
Copeptin
Time frame: 14 days
Copeptin
Time frame: 21 days
Copeptin
Time frame: 28 days
Aldosterone
Time frame: 7 days
Aldosterone
Time frame: 14 days
Aldosterone
Time frame: 21 days
Aldosterone
Time frame: 28 days
Renin
Time frame: 7 days
Renin
Time frame: 14 days
Renin
Time frame: 21 days
Renin
Time frame: 28 days
MR-proANP
Time frame: 7 days
MR-proANP
Time frame: 14 days
MR-proANP
Time frame: 21 days
MR-proANP
Time frame: 28 days
N terminal (NT)-proBNP
Time frame: 7 days
NT-proBNP
Time frame: 14 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 13 Dec 2021.
- Derived from this study: PubMed 42522233Kustos-Toth E, Beck J, Seeger L, Monnerat S, Bathelt C, Refardt J, Christ-Crain M. Hyponatremia correction is associated with increased brain-derived neurotrophic factor levels: A pilot secondary analysis of a randomized, double-blind, placebo-controlled, crossover trial. J Neuroendocrinol. 2026 Aug;38(8):e70238. doi: 10.1111/jne.70238.
- Derived from this study: PubMed 37098131Monnerat S, Refardt J, Potasso L, Meier C, Christ-Crain M. An Increase in Plasma Sodium Levels Is Associated With an Increase in Osteoblast Function in Chronic SIAD. J Clin Endocrinol Metab. 2023 Sep 18;108(10):e1027-e1033. doi: 10.1210/clinem/dgad238.
- Derived from this study: PubMed 36396331Refardt J, Imber C, Nobbenhuis R, Sailer CO, Haslbauer A, Monnerat S, Bathelt C, Vogt DR, Berres M, Winzeler B, Bridenbaugh SA, Christ-Crain M. Treatment Effect of the SGLT2 Inhibitor Empagliflozin on Chronic Syndrome of Inappropriate Antidiuresis: Results of a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial. J Am Soc Nephrol. 2023 Feb 1;34(2):322-332. doi: 10.1681/ASN.2022050623. Epub 2022 Nov 17.
- Individual participant dataSharing planned: No
Related trials for SIAD - Syndrome of Inappropriate Antidiuresis
Recruiting
Urea for Treatment of Hyponatremia in Patients With SIAD Unresponsive to Fluid Restriction
SIAD - Syndrome of Inappropriate Antidiuresis
Recruiting
Protein Supplementation in Hyponatremia Due to the Syndrome of Inappropriate Antidiuresis
Hyponatremia, Syndrome of Inappropriate Antidiuresis
RecruitingObservational study
National Registry of Rare Kidney Diseases
Adenine Phosphoribosyltransferase Deficiency, AH Amyloidosis
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. Dr. MD study director
University Hopsital 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 Empagliflozin 25mg in people with SIAD - Syndrome of Inappropriate Antidiuresis and Hyponatremia, 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 12 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 13 Dec 2021. 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?
Change in Serum Sodium concentration (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03202667, which also lists 3 linked publications.
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 13 Dec 2021.