NCT03202667

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
17

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Dec 2017

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 27, 2017

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 28, 2017

Completed
6 months until next milestone

Study Start

First participant enrolled

December 15, 2017

Completed
3.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 26, 2021

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

December 6, 2021

Completed
Last Updated

December 13, 2021

Status Verified

December 1, 2021

Enrollment Period

3.7 years

First QC Date

June 27, 2017

Last Update Submit

December 10, 2021

Conditions

SIAD - Syndrome of Inappropriate AntidiuresisHyponatremia

Keywords

SGLT2-inhibitorTreatment

Outcome Measures

Primary Outcomes (1)

  • Change in Serum Sodium concentration

    Difference in serum sodium concentration in mmol/l after 28 days of treatment

    28 days

Secondary Outcomes (72)

  • Change in Serum sodium concentration

    21 days

  • Change in Serum electrolytes

    28 days

  • Urinary electrolytes

    7 days

  • Urinary electrolytes

    14 days

  • Urinary electrolytes

    21 days

  • +67 more secondary outcomes

Study Arms (2)

Empagliflozin

ACTIVE COMPARATOR

Treatment with empagliflozin 25mg tablets once daily for 28 days

Drug: Empagliflozin 25mg

Placebo

PLACEBO COMPARATOR

Treatment with Placebo tablets once daily for 28 days

Drug: Placebo

Interventions

Empagliflozin 25mgDRUG

Treatment with empagliflozin 25mg once daily for 28 days

Empagliflozin
PlaceboDRUG

Treatment with Placebo oral tablet once daily for 28 days

Placebo

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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)

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital Basel

Basel, 4031, Switzerland

Location

Related Publications (2)

  • Monnerat 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.

    PMID: 37098131DERIVED

  • 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.

    PMID: 36396331DERIVED

MeSH Terms

Conditions

Inappropriate ADH SyndromeHyponatremia

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Pituitary DiseasesHypothalamic DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesWater-Electrolyte ImbalanceMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Study Officials

  • Mirjam Christ-Crain, Prof. Dr. MD

    University Hopsital Basel

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 27, 2017

First Posted

June 28, 2017

Study Start

December 15, 2017

Primary Completion

August 26, 2021

Study Completion

December 6, 2021

Last Updated

December 13, 2021

Record last verified: 2021-12

Data Sharing

IPD Sharing
Will not share

Locations

CH(1)