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Completed

NCT Number: NCT03202667

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

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.

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Key information

Conditions

SIAD - Syndrome of Inappropriate Antidiuresis Brain Diseases Central Nervous System Diseases Endocrine System Diseases Hyponatremia Hypothalamic Diseases Inappropriate ADH Syndrome Metabolic Diseases Nervous System Diseases Nutritional and Metabolic Diseases Pituitary Diseases Water-Electrolyte Imbalance

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2 / Phase 3

Primary location

University Hospital Basel

Basel, 4031, Switzerland

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Empagliflozin 25mg

Drug

Treatment with empagliflozin 25mg once daily for 28 days

Placebo

Drug

Treatment with Placebo oral tablet once daily for 28 days

Primary outcomes

  1. Change in Serum Sodium concentration

    Time frame: 28 days

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

Secondary outcomes

  1. Change in Serum sodium concentration

    Time frame: 21 days

    Serum sodium concentration 1, 2 and 3 weeks of treatment

  2. Change in Serum electrolytes

    Time frame: 28 days

    Serum electrolytes after 1, 2, 3 and 4 weeks of treatment

  3. Urinary electrolytes

    Time frame: 7 days

    Urinary electrolytes after 1 week of treatment

  4. Urinary electrolytes

    Time frame: 14 days

    Urinary electrolytes after 2 weeks of treatment

  5. Urinary electrolytes

    Time frame: 21 days

    Urinary electrolytes after 3 weeks of treatment

  6. Urinary electrolytes

    Time frame: 28 days

    Urinary electrolytes after 4 weeks of treatment

  7. Serum osmolality

    Time frame: 7 days

    Serum osmolality after 1 week of treatment

  8. Serum osmolality

    Time frame: 14 days

    Serum osmolality after 2 weeks of treatment

  9. Serum osmolality

    Time frame: 21 days

    Serum osmolality after 3 weeks of treatment

  10. Serum osmolality

    Time frame: 28 days

    Serum osmolality after 4 weeks of treatment

  11. Urinary osmolality

    Time frame: 7 days

    Urinary osmolality after 1 week of treatment

  12. Urinary osmolality

    Time frame: 14 days

    Urinary osmolality after 2 weeks of treatment

  13. Urinary osmolality

    Time frame: 21 days

    Urinary osmolality after3 weeks of treatment

  14. Urinary osmolality

    Time frame: 28 days

    Urinary osmolality after 4 weeks of treatment

  15. Serum glucose

    Time frame: 7 days

    Serum glucose after 1 week of treatment

  16. Serum glucose

    Time frame: 14 days

    Serum glucose after 2 weeks of treatment

  17. Serum glucose

    Time frame: 21 days

    Serum glucose after 3 weeks of treatment

  18. Serum glucose

    Time frame: 28 days

    Serum glucose after 4 weeks of treatment

  19. Urinary glucose

    Time frame: 7 days

    Urinary glucose after 1 week of treatment

  20. Urinary glucose

    Time frame: 14 days

    Urinary glucose after 2 weeks of treatment

  21. Urinary glucose

    Time frame: 21 days

    Urinary glucose after 3 weeks of treatment

  22. Urinary glucose

    Time frame: 28 days

    Urinary glucose after 4 weeks of treatment

  23. Copeptin

    Time frame: 7 days

    Plasma copeptin after 1 week of treatment

  24. Copeptin

    Time frame: 14 days

    Plasma copeptin after 2 weeks of treatment

  25. Copeptin

    Time frame: 21 days

    Plasma copeptin after3 weeks of treatment

  26. Copeptin

    Time frame: 28 days

    Plasma copeptin after 4 weeks of treatment

  27. Aldosterone

    Time frame: 7 days

    Plasma aldosterone after 1 week of treatment

  28. Aldosterone

    Time frame: 14 days

    Plasma aldosterone after 2 weeks of treatment

  29. Aldosterone

    Time frame: 21 days

    Plasma aldosterone after 3 weeks of treatment

  30. Aldosterone

    Time frame: 28 days

    Plasma aldosterone after 4 weeks of treatment

  31. Renin

    Time frame: 7 days

    Plasma renin after 1 week of treatment

  32. Renin

    Time frame: 14 days

    Plasma renin after 2 weeks of treatment

  33. Renin

    Time frame: 21 days

    Plasma renin after 3 weeks of treatment

  34. Renin

    Time frame: 28 days

    Plasma renin after 4 weeks of treatment

  35. MR-proANP

    Time frame: 7 days

    Plasma MR-proANP after 1 week of treatment

  36. MR-proANP

    Time frame: 14 days

    Plasma MR-proANP after 2 weeks of treatment

  37. MR-proANP

    Time frame: 21 days

    Plasma MR-proANP after 3 weeks of treatment

  38. MR-proANP

    Time frame: 28 days

    Plasma MR-proANP after 4 weeks of treatment

  39. N terminal (NT)-proBNP

    Time frame: 7 days

    Plasma NT-proBNP after 1 week of treatment

  40. NT-proBNP

    Time frame: 14 days

    Plasma NT-proBNP after 2 weeks of treatment

  41. NT-proBNP

    Time frame: 21 days

    Plasma NT-proBNP after 3 weeks of treatment

  42. NT-proBNP

    Time frame: 28 days

    Plasma NT-proBNP after 4 weeks of treatment

  43. P1NP

    Time frame: 7 days

    Plasma P1NP after 1 week of treatment

  44. P1NP

    Time frame: 14 days

    Plasma P1NP after 2 weeks of treatment

  45. P1NP

    Time frame: 21 days

    Plasma P1NP after 3 weeks of treatment

  46. P1NP

    Time frame: 28 days

    Plasma P1NP after 4 weeks of treatment

  47. CTx

    Time frame: 7 days

    Plasma CTx after 1 week of treatment

  48. CTx

    Time frame: 14 days

    Plasma CTx after 2 weeks of treatment

  49. CTx

    Time frame: 21 days

    Plasma CTx after 3 weeks of treatment

  50. CTx

    Time frame: 28 days

    Plasma CTx after 4 weeks of treatment

  51. Osteocalcin

    Time frame: 7 days

    Plasma Osteocalcin after 1 week of treatment

  52. Osteocalcin

    Time frame: 14 days

    Plasma Osteocalcin after 2 weeks of treatment

  53. Osteocalcin

    Time frame: 21 days

    Plasma Osteocalcin after 3 weeks of treatment

  54. Osteocalcin

    Time frame: 28 days

    Plasma Osteocalcin after 4 weeks of treatment

  55. General well being (assessed by VAS)

    Time frame: 28 days

    General well being after 1, 2, 3 and 4 weeks of treatment

  56. Headache (assessed by VAS)

    Time frame: 28 days

    Headache after 1, 2, 3 and 4 weeks of treatment

  57. Vertigo (assessed by VAS)

    Time frame: 28 days

    vertigo after 1, 2, 3 and 4 weeks of treatment

  58. Nausea (assessed by VAS)

    Time frame: 28 days

    Nausea after 1, 2, 3 and 4 weeks of treatment

  59. Malaise (assessed by VAS)

    Time frame: 28 days

    Malaise after 1, 2, 3 and 4 weeks of treatment

  60. Body weight (kg)

    Time frame: 28 days

    Body weight after 1, 2, 3 and 4 weeks of treatment

  61. Blood pressure (mmHg)

    Time frame: 28 days

    Blood pressure after 1, 2, 3 and 4 weeks of treatment

  62. Heart rate (bpm)

    Time frame: 28 days

    Heart rate after 1, 2, 3 and 4 weeks of treatment

  63. Neurocognitive function (assessed by MOCA)

    Time frame: 28 days

    change in Neurocognitive function (baseline versus after 4 weeks of Treatment)

  64. Muscle strength (measured by grip strength test)

    Time frame: 28 days

    Change in Muscle strength (baseline vs after 4 weeks of Treatment)

  65. Gait Dynamics (measured by gait Analysis)

    Time frame: 28 days

    Gait dynamics baseline vs after 4 weeks of treatment

  66. Hemodynamic Parameters (measured by thoracic electrical bioimpedance)

    Time frame: 28 days

    Hemodynamic parameters baseline vs after 4 weeks of treatment

  67. Body fluid volume (measured by bioimpedance spectroscopy)

    Time frame: 28 days

    Body fluid volume baseline vs after 4 weeks of treatment

  68. Amount of Fluid intake in ml

    Time frame: 28 days

    Fluid intake after 1, 2, 3 and 4 weeks of treatment

  69. Number of Falls

    Time frame: 30 days

    Rate of falls during observation phase

  70. number of Fractures

    Time frame: 30 days

    Rate of fractures during observation phase

  71. number of Hospital admissions

    Time frame: 30 days

    Rate of Hospital admissions during observation phase

  72. Hyponatremia recurrence

    Time frame: 30 days

    Rate of hyponatremia recurrence during 30day follow up

Sponsors and collaborators

Lead sponsor

University Hospital, Basel, Switzerland

Other

Registry information

Acronym: SANDx

Important dates

Study start
2017
Primary completion
2021
Study completion
2021
First posted
Jun 28, 2017
Registry last updated
Dec 13, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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