Effects of the SGLT2-inhibitor Empagliflozin on Patients With Chronic SIADH - the SANDx Study

Hyponatremia Clinical Trial

— SANDx  

Official title:

Effects of the SGLT2-inhibitor Empagliflozin on Patients With Chronic SIADH - the SANDx Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03202667
• Other study ID #: 2017-00701
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: December 15, 2017
• Est. completion date: December 6, 2021

Study information

• Verified date: December 2021
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: December 6, 2021
• Est. primary completion date: August 26, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

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

Exclusion Criteria:

• 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)

• 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)

Related Conditions & MeSH terms

• Hyponatremia
• Inappropriate ADH Syndrome
• SIAD - Syndrome of Inappropriate Antidiuresis

Intervention

Drug:
• Empagliflozin 25mg
Treatment with empagliflozin 25mg once daily for 28 days
• Placebo
Treatment with Placebo oral tablet once daily for 28 days

Locations

Country	Name	City	State
Switzerland	University Hospital Basel	Basel

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Serum Sodium concentration	Difference in serum sodium concentration in mmol/l after 28 days of treatment	28 days
Secondary	Change in Serum sodium concentration	Serum sodium concentration 1, 2 and 3 weeks of treatment	21 days
Secondary	Change in Serum electrolytes	Serum electrolytes after 1, 2, 3 and 4 weeks of treatment	28 days
Secondary	Urinary electrolytes	Urinary electrolytes after 1 week of treatment	7 days
Secondary	Urinary electrolytes	Urinary electrolytes after 2 weeks of treatment	14 days
Secondary	Urinary electrolytes	Urinary electrolytes after 3 weeks of treatment	21 days
Secondary	Urinary electrolytes	Urinary electrolytes after 4 weeks of treatment	28 days
Secondary	Serum osmolality	Serum osmolality after 1 week of treatment	7 days
Secondary	Serum osmolality	Serum osmolality after 2 weeks of treatment	14 days
Secondary	Serum osmolality	Serum osmolality after 3 weeks of treatment	21 days
Secondary	Serum osmolality	Serum osmolality after 4 weeks of treatment	28 days
Secondary	Urinary osmolality	Urinary osmolality after 1 week of treatment	7 days
Secondary	Urinary osmolality	Urinary osmolality after 2 weeks of treatment	14 days
Secondary	Urinary osmolality	Urinary osmolality after3 weeks of treatment	21 days
Secondary	Urinary osmolality	Urinary osmolality after 4 weeks of treatment	28 days
Secondary	Serum glucose	Serum glucose after 1 week of treatment	7 days
Secondary	Serum glucose	Serum glucose after 2 weeks of treatment	14 days
Secondary	Serum glucose	Serum glucose after 3 weeks of treatment	21 days
Secondary	Serum glucose	Serum glucose after 4 weeks of treatment	28 days
Secondary	Urinary glucose	Urinary glucose after 1 week of treatment	7 days
Secondary	Urinary glucose	Urinary glucose after 2 weeks of treatment	14 days
Secondary	Urinary glucose	Urinary glucose after 3 weeks of treatment	21 days
Secondary	Urinary glucose	Urinary glucose after 4 weeks of treatment	28 days
Secondary	Copeptin	Plasma copeptin after 1 week of treatment	7 days
Secondary	Copeptin	Plasma copeptin after 2 weeks of treatment	14 days
Secondary	Copeptin	Plasma copeptin after3 weeks of treatment	21 days
Secondary	Copeptin	Plasma copeptin after 4 weeks of treatment	28 days
Secondary	Aldosterone	Plasma aldosterone after 1 week of treatment	7 days
Secondary	Aldosterone	Plasma aldosterone after 2 weeks of treatment	14 days
Secondary	Aldosterone	Plasma aldosterone after 3 weeks of treatment	21 days
Secondary	Aldosterone	Plasma aldosterone after 4 weeks of treatment	28 days
Secondary	Renin	Plasma renin after 1 week of treatment	7 days
Secondary	Renin	Plasma renin after 2 weeks of treatment	14 days
Secondary	Renin	Plasma renin after 3 weeks of treatment	21 days
Secondary	Renin	Plasma renin after 4 weeks of treatment	28 days
Secondary	MR-proANP	Plasma MR-proANP after 1 week of treatment	7 days
Secondary	MR-proANP	Plasma MR-proANP after 2 weeks of treatment	14 days
Secondary	MR-proANP	Plasma MR-proANP after 3 weeks of treatment	21 days
Secondary	MR-proANP	Plasma MR-proANP after 4 weeks of treatment	28 days
Secondary	N terminal (NT)-proBNP	Plasma NT-proBNP after 1 week of treatment	7 days
Secondary	NT-proBNP	Plasma NT-proBNP after 2 weeks of treatment	14 days
Secondary	NT-proBNP	Plasma NT-proBNP after 3 weeks of treatment	21 days
Secondary	NT-proBNP	Plasma NT-proBNP after 4 weeks of treatment	28 days
Secondary	P1NP	Plasma P1NP after 1 week of treatment	7 days
Secondary	P1NP	Plasma P1NP after 2 weeks of treatment	14 days
Secondary	P1NP	Plasma P1NP after 3 weeks of treatment	21 days
Secondary	P1NP	Plasma P1NP after 4 weeks of treatment	28 days
Secondary	CTx	Plasma CTx after 1 week of treatment	7 days
Secondary	CTx	Plasma CTx after 2 weeks of treatment	14 days
Secondary	CTx	Plasma CTx after 3 weeks of treatment	21 days
Secondary	CTx	Plasma CTx after 4 weeks of treatment	28 days
Secondary	Osteocalcin	Plasma Osteocalcin after 1 week of treatment	7 days
Secondary	Osteocalcin	Plasma Osteocalcin after 2 weeks of treatment	14 days
Secondary	Osteocalcin	Plasma Osteocalcin after 3 weeks of treatment	21 days
Secondary	Osteocalcin	Plasma Osteocalcin after 4 weeks of treatment	28 days
Secondary	General well being (assessed by VAS)	General well being after 1, 2, 3 and 4 weeks of treatment	28 days
Secondary	Headache (assessed by VAS)	Headache after 1, 2, 3 and 4 weeks of treatment	28 days
Secondary	Vertigo (assessed by VAS)	vertigo after 1, 2, 3 and 4 weeks of treatment	28 days
Secondary	Nausea (assessed by VAS)	Nausea after 1, 2, 3 and 4 weeks of treatment	28 days
Secondary	Malaise (assessed by VAS)	Malaise after 1, 2, 3 and 4 weeks of treatment	28 days
Secondary	Body weight (kg)	Body weight after 1, 2, 3 and 4 weeks of treatment	28 days
Secondary	Blood pressure (mmHg)	Blood pressure after 1, 2, 3 and 4 weeks of treatment	28 days
Secondary	Heart rate (bpm)	Heart rate after 1, 2, 3 and 4 weeks of treatment	28 days
Secondary	Neurocognitive function (assessed by MOCA)	change in Neurocognitive function (baseline versus after 4 weeks of Treatment)	28 days
Secondary	Muscle strength (measured by grip strength test)	Change in Muscle strength (baseline vs after 4 weeks of Treatment)	28 days
Secondary	Gait Dynamics (measured by gait Analysis)	Gait dynamics baseline vs after 4 weeks of treatment	28 days
Secondary	Hemodynamic Parameters (measured by thoracic electrical bioimpedance)	Hemodynamic parameters baseline vs after 4 weeks of treatment	28 days
Secondary	Body fluid volume (measured by bioimpedance spectroscopy)	Body fluid volume baseline vs after 4 weeks of treatment	28 days
Secondary	Amount of Fluid intake in ml	Fluid intake after 1, 2, 3 and 4 weeks of treatment	28 days
Secondary	Number of Falls	Rate of falls during observation phase	30 days
Secondary	number of Fractures	Rate of fractures during observation phase	30 days
Secondary	number of Hospital admissions	Rate of Hospital admissions during observation phase	30 days
Secondary	Hyponatremia recurrence	Rate of hyponatremia recurrence during 30day follow up	30 days