Effects of the SGLT2-inhibitor Empagliflozin on Patients With Chronic SIADH - the SANDx Study
- Conditions
- SIAD - Syndrome of Inappropriate AntidiuresisHyponatremia
- Interventions
- Drug: Placebo
- Registration Number
- NCT03202667
- Lead Sponsor
- University Hospital, Basel, Switzerland
- Brief 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 17
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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- CROSSOVER
- Arm && Interventions
Group Intervention Description Placebo Placebo Treatment with Placebo tablets once daily for 28 days Empagliflozin Empagliflozin 25mg Treatment with empagliflozin 25mg tablets once daily for 28 days
- Primary Outcome Measures
Name Time Method Change in Serum Sodium concentration 28 days Difference in serum sodium concentration in mmol/l after 28 days of treatment
- Secondary Outcome Measures
Name Time Method Change in Serum sodium concentration 21 days Serum sodium concentration 1, 2 and 3 weeks of treatment
Urinary electrolytes 28 days Urinary electrolytes after 4 weeks of treatment
Serum osmolality 28 days Serum osmolality after 4 weeks of treatment
Nausea (assessed by VAS) 28 days Nausea after 1, 2, 3 and 4 weeks of treatment
Change in Serum electrolytes 28 days Serum electrolytes after 1, 2, 3 and 4 weeks of treatment
Urinary osmolality 28 days Urinary osmolality after 4 weeks of treatment
Serum glucose 28 days Serum glucose after 4 weeks of treatment
Urinary glucose 28 days Urinary glucose after 4 weeks of treatment
Copeptin 28 days Plasma copeptin after 4 weeks of treatment
Aldosterone 28 days Plasma aldosterone after 4 weeks of treatment
Renin 28 days Plasma renin after 4 weeks of treatment
NT-proBNP 28 days Plasma NT-proBNP after 4 weeks of treatment
Neurocognitive function (assessed by MOCA) 28 days change in Neurocognitive function (baseline versus after 4 weeks of Treatment)
Muscle strength (measured by grip strength test) 28 days Change in Muscle strength (baseline vs after 4 weeks of Treatment)
Body fluid volume (measured by bioimpedance spectroscopy) 28 days Body fluid volume baseline vs after 4 weeks of treatment
Amount of Fluid intake in ml 28 days Fluid intake after 1, 2, 3 and 4 weeks of treatment
Number of Falls 30 days Rate of falls during observation phase
number of Hospital admissions 30 days Rate of Hospital admissions during observation phase
MR-proANP 28 days Plasma MR-proANP after 4 weeks of treatment
N terminal (NT)-proBNP 7 days Plasma NT-proBNP after 1 week of treatment
P1NP 28 days Plasma P1NP after 4 weeks of treatment
CTx 28 days Plasma CTx after 4 weeks of treatment
Osteocalcin 28 days Plasma Osteocalcin after 4 weeks of treatment
General well being (assessed by VAS) 28 days General well being after 1, 2, 3 and 4 weeks of treatment
Malaise (assessed by VAS) 28 days Malaise after 1, 2, 3 and 4 weeks of treatment
number of Fractures 30 days Rate of fractures during observation phase
Headache (assessed by VAS) 28 days Headache after 1, 2, 3 and 4 weeks of treatment
Vertigo (assessed by VAS) 28 days vertigo after 1, 2, 3 and 4 weeks of treatment
Body weight (kg) 28 days Body weight after 1, 2, 3 and 4 weeks of treatment
Blood pressure (mmHg) 28 days Blood pressure after 1, 2, 3 and 4 weeks of treatment
Heart rate (bpm) 28 days Heart rate after 1, 2, 3 and 4 weeks of treatment
Gait Dynamics (measured by gait Analysis) 28 days Gait dynamics baseline vs after 4 weeks of treatment
Hemodynamic Parameters (measured by thoracic electrical bioimpedance) 28 days Hemodynamic parameters baseline vs after 4 weeks of treatment
Hyponatremia recurrence 30 days Rate of hyponatremia recurrence during 30day follow up
Trial Locations
- Locations (1)
University Hospital Basel
🇨🇭Basel, Switzerland