Clinical trial NCT06821802: Protein Supplementation in Hyponatremia Due to the Syndrome of Inappropriate Antidiuresis
Official title: Effect of Protein Supplementation in Hospitalized Patients With Hyponatremia Due to the Syndrome of Inappropriate Antidiuresis - a Monocentric Randomized Open-label Pragmatic Active-controlled Trial - the TREASUREx Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Hyponatremia
Syndrome of Inappropriate Antidiuresis
Keywords: dysregulated arginine vasopressin (AVP) secretion
increased renal AVP sensitivity
protein supplementation
fluid restriction
Lead sponsor: University Hospital, Basel, Switzerland
Sponsor class: OTHER
First posted: 2025-02-12
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this study is to assess the impact of protein supplementation on hyponatremia caused by the syndrome of inappropriate antidiuresis during hospitalization.

Detailed description: Hyponatremia (plasma sodium \<135 mmol/L) is the most common electrolyte disorder, affecting up to 30% of hospitalized patients. Chronic hyponatremia (\>48 hours) is linked to longer hospital stays, higher costs, increased mortality, and morbidity (e.g., falls, fractures, cognitive deficits). The most common cause of euvolemic hyponatremia is syndrome of inappropriate antidiuresis (SIAD), characterized by excessive water retention due to dysregulated vasopressin activity. Treatment options include fluid restriction or increasing water excretion with AVP antagonists, SGLT2 inhibitors, or oral urea.

A recent trial showed that protein supplementation can induce osmotic diuresis and raise sodium levels similarly to oral urea, with better tolerability. Since protein supplementation is often used in hospitalized patients with malnutrition, this study aims to compare its acceptability to fluid restriction in hospitalized SIAD patients. This head-to-head superiority trial will randomize patients to receive either 80 g of dietary protein daily or fluid restriction (1000 mL/day) for up to 5 days. The hypothesis is that protein supplementation is significantly more acceptable to patients than fluid restriction, ultimately improving treatment outcomes.

Eligibility criteria: Inclusion Criteria:

* Adult patients with confirmed SIAD during the hospital stay or at screening, defined by:
* Plasma sodium concentration \<135 mmol/L
* Plasma osmolality \<300 mOsm/kg
* Urine osmolality \>100 mOsm/kg
* Urine sodium concentration \>30 mmol/L
* Clinical euvolemia (no signs of hypovolemia or hypervolemia)

Exclusion Criteria:

* Lactose intolerance, celiac disease, milk protein allergy, soy allergy, nuts allergy, or hypersensitivity to components of the protein supplement.
* Inborn metabolic disorders affecting carbohydrate, lipid, or protein metabolism.
* Severe symptomatic hyponatremia requiring 3% NaCl or intensive care.
* Type 1 diabetes or uncontrolled type 2 diabetes (HbA1c \>8.0%).
* Uncontrolled severe hypothyroidism or adrenal insufficiency.
* eGFR \<60 mL/min/1.73 m² (KDIGO G3-5) or end-stage renal disease.
* Severe hepatic impairment or advanced symptomatic liver disease.
* New (within the last five days) treatment with diuretics, SGLT2 inhibitors, lithium, urea, vaptans
* Pregnancy, breastfeeding, or plans to become pregnant during the study.
* End-of-life care, current participation in another intervention study, or inability to give informed consent or follow study procedures.

Primary outcomes:
measure: Acceptability of Intervention Measure (AIM) questionnaire
timeFrame: On day 5 (or discharge)
Secondary outcomes:
measure: Plasma sodium levels
timeFrame: Daily measurements from the day of inclusion to day 5
measure: Estimated glomerular filtration rate (eGFR)
timeFrame: On the day of inclusion and on day 5
measure: Changes in blood electrolytes
timeFrame: On the day of inclusion and on day 5
measure: Changes in urine electrolytes
timeFrame: On the day of inclusion and on day 5
measure: Changes in glucose levels
timeFrame: On the day of inclusion and on day 5
measure: Changes kidney parameters
timeFrame: On the day of inclusion and on day 5
measure: Plasma sodium levels one day after treatment start
timeFrame: On the day of inclusion and 12-36 hours after treatment initiation
measure: Endocrine parameters
timeFrame: On the day of inclusion and on day 5
measure: General well-being
timeFrame: On the day of inclusion and on day 5
measure: Symptoms of hyponatremia
timeFrame: On the day of inclusion and on day 5
measure: Fluid intake
timeFrame: Daily measurements from the day of inclusion to day 5
measure: Changes in body weight
timeFrame: On the day of inclusion and on day 5
measure: Changes in blood pressure
timeFrame: On the day of inclusion and on day 5
measure: Changes in heart rate
timeFrame: On the day of inclusion and on day 5
measure: Differences in clinical outcomes - length of hospital stays
timeFrame: Daily from the day of inclusion to day 5
measure: Need for additional hyponatremia treatment and treatment escalation
timeFrame: Daily from the day of inclusion to day 5
measure: Treatment compliance
timeFrame: Daily from the day of inclusion to day 5
measure: Quality of life (EQ-5D-5L) questionnaire
timeFrame: On the day of inclusion and on day 5
Other outcomes:
Locations:
city: Basel
country: Switzerland
facility: University Hospital Basel
Study officials:
affiliation: Universitätsspital Basel
name: Mirjam Christ-Crain, Prof. MD
role: PRINCIPAL_INVESTIGATOR
References: