Clinical trial NCT03202667: Effects of the SGLT2-inhibitor Empagliflozin on Patients With Chronic SIADH - the SANDx Study
Official title: Effects of the SGLT2-inhibitor Empagliflozin on Patients With Chronic SIADH - the SANDx Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: SIAD - Syndrome of Inappropriate Antidiuresis
Hyponatremia
Keywords: SGLT2-inhibitor
Treatment
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2017-06-28
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Change in Serum Sodium concentration
timeFrame: 28 days
Secondary outcomes:
measure: Change in Serum sodium concentration
timeFrame: 21 days
measure: Change in Serum electrolytes
timeFrame: 28 days
measure: Urinary electrolytes
timeFrame: 7 days
measure: Urinary electrolytes
timeFrame: 14 days
measure: Urinary electrolytes
timeFrame: 21 days
measure: Urinary electrolytes
timeFrame: 28 days
measure: Serum osmolality
timeFrame: 7 days
measure: Serum osmolality
timeFrame: 14 days
measure: Serum osmolality
timeFrame: 21 days
measure: Serum osmolality
timeFrame: 28 days
measure: Urinary osmolality
timeFrame: 7 days
measure: Urinary osmolality
timeFrame: 14 days
measure: Urinary osmolality
timeFrame: 21 days
measure: Urinary osmolality
timeFrame: 28 days
measure: Serum glucose
timeFrame: 7 days
measure: Serum glucose
timeFrame: 14 days
measure: Serum glucose
timeFrame: 21 days
measure: Serum glucose
timeFrame: 28 days
measure: Urinary glucose
timeFrame: 7 days
measure: Urinary glucose
timeFrame: 14 days
measure: Urinary glucose
timeFrame: 21 days
measure: Urinary glucose
timeFrame: 28 days
measure: Copeptin
timeFrame: 7 days
measure: Copeptin
timeFrame: 14 days
measure: Copeptin
timeFrame: 21 days
measure: Copeptin
timeFrame: 28 days
measure: Aldosterone
timeFrame: 7 days
measure: Aldosterone
timeFrame: 14 days
measure: Aldosterone
timeFrame: 21 days
measure: Aldosterone
timeFrame: 28 days
measure: Renin
timeFrame: 7 days
measure: Renin
timeFrame: 14 days
measure: Renin
timeFrame: 21 days
measure: Renin
timeFrame: 28 days
measure: MR-proANP
timeFrame: 7 days
measure: MR-proANP
timeFrame: 14 days
measure: MR-proANP
timeFrame: 21 days
measure: MR-proANP
timeFrame: 28 days
measure: N terminal (NT)-proBNP
timeFrame: 7 days
measure: NT-proBNP
timeFrame: 14 days
measure: NT-proBNP
timeFrame: 21 days
measure: NT-proBNP
timeFrame: 28 days
measure: P1NP
timeFrame: 7 days
measure: P1NP
timeFrame: 14 days
measure: P1NP
timeFrame: 21 days
measure: P1NP
timeFrame: 28 days
measure: CTx
timeFrame: 7 days
measure: CTx
timeFrame: 14 days
measure: CTx
timeFrame: 21 days
measure: CTx
timeFrame: 28 days
measure: Osteocalcin
timeFrame: 7 days
measure: Osteocalcin
timeFrame: 14 days
measure: Osteocalcin
timeFrame: 21 days
measure: Osteocalcin
timeFrame: 28 days
measure: General well being (assessed by VAS)
timeFrame: 28 days
measure: Headache (assessed by VAS)
timeFrame: 28 days
measure: Vertigo (assessed by VAS)
timeFrame: 28 days
measure: Nausea (assessed by VAS)
timeFrame: 28 days
measure: Malaise (assessed by VAS)
timeFrame: 28 days
measure: Body weight (kg)
timeFrame: 28 days
measure: Blood pressure (mmHg)
timeFrame: 28 days
measure: Heart rate (bpm)
timeFrame: 28 days
measure: Neurocognitive function (assessed by MOCA)
timeFrame: 28 days
measure: Muscle strength (measured by grip strength test)
timeFrame: 28 days
measure: Gait Dynamics (measured by gait Analysis)
timeFrame: 28 days
measure: Hemodynamic Parameters (measured by thoracic electrical bioimpedance)
timeFrame: 28 days
measure: Body fluid volume (measured by bioimpedance spectroscopy)
timeFrame: 28 days
measure: Amount of Fluid intake in ml
timeFrame: 28 days
measure: Number of Falls
timeFrame: 30 days
measure: number of Fractures
timeFrame: 30 days
measure: number of Hospital admissions
timeFrame: 30 days
measure: Hyponatremia recurrence
timeFrame: 30 days
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: University Hopsital Basel
name: Mirjam Christ-Crain, Prof. Dr. MD
role: STUDY_DIRECTOR
References:
citation: Refardt 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.