ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03202667
Recruitment Status : Recruiting
First Posted : June 28, 2017
Last Update Posted : January 16, 2018
Sponsor:
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
SIAD - Syndrome of Inappropriate Antidiuresis Hyponatremia Drug: Empagliflozin 25mg Drug: Placebo Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 16 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of the SGLT2-inhibitor Empagliflozin on Patients With Chronic SIADH - the SANDx Study
Actual Study Start Date : December 15, 2017
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Empagliflozin
Treatment with empagliflozin 25mg tablets once daily for 28 days
Drug: Empagliflozin 25mg
Treatment with empagliflozin 25mg once daily for 28 days

Placebo Comparator: Placebo
Treatment with Placebo tablets once daily for 28 days
Drug: Placebo
Treatment with Placebo oral tablet once daily for 28 days




Primary Outcome Measures :
  1. Change in Serum Sodium concentration [ Time Frame: 28 days ]
    Difference in serum sodium concentration in mmol/l after 28 days of treatment


Secondary Outcome Measures :
  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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03202667


Contacts
Contact: Julie Refardt, Dr. MD +41(0)61 2652525 Zentrale Julie.Refardt@usb.ch

Locations
Switzerland
University Hospital Basel Recruiting
Basel, Switzerland, 4031
Contact: Julie Refardt, Dr.    +41(0)61 2652525 Zentrale    julie.refardt@usb.ch   
Contact: Mirjam Christ-Crain, Prof       mirjam.christ@usb.ch   
Sponsors and Collaborators
University Hospital, Basel, Switzerland
Investigators
Study Director: Mirjam Christ-Crain, Prof. Dr. MD University Hopsital Basel

Responsible Party: University Hospital, Basel, Switzerland
ClinicalTrials.gov Identifier: NCT03202667     History of Changes
Other Study ID Numbers: 2017-00701
First Posted: June 28, 2017    Key Record Dates
Last Update Posted: January 16, 2018
Last Verified: January 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University Hospital, Basel, Switzerland:
SGLT2-inhibitor
Treatment

Additional relevant MeSH terms:
Hyponatremia
Inappropriate ADH Syndrome
Water-Electrolyte Imbalance
Metabolic Diseases
Pituitary Diseases
Hypothalamic Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Endocrine System Diseases
Empagliflozin
Hypoglycemic Agents
Physiological Effects of Drugs