Syndrome of Inappropriate Antidiuresis (SIAD)TREASURENCT04987385
Effect of Protein Supplementation on Plasma Sodium Levels and Urinary Urea Excretion in Patients With SIAD
A study testing Protein supplementation and Oral urea in people with Syndrome of Inappropriate Antidiuresis (SIAD), run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
This study aims to investigate whether a 7-day dietary high protein supplementation of 90 grams per day increases plasma sodium levels in hyponatremic patients with chronic SIAD. Enrolled patients will receive first dietary high protein supplementation for one week. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Syndrome of Inappropriate Antidiuresis (SIAD)
- What is being tested?
- Protein supplementation and Oral urea
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteSwitzerland
- Study dates
- 8 Oct 2021to 20 Feb 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- previous documented diagnosis of chronic SIAD
- confirmed diagnosis of SIAD at screening visit defined as:
- plasma sodium concentration <135 mmol/L, measured in lithium heparin plasma
- Plasma osmolality <300 mOsm/kg
- Urine osmolality >100 mOsm/kg
- Urine sodium concentration >30mmol/l
- Clinical euvolemia, defined as an absence of signs of hypovolemia (orthostasis, tachycardia, decreased skin turgor, dry mucous membranes) or hypervolemia (edema, ascites)
Who cannot join
- lactose intolerance, celiac disease, milk protein allergy, soja allergy, nuts allergy or known hypersensitivity or allergy to one of the components of the protein supplementation (Whey Protein®, foodspring GmbH, Germany or Clear Whey Isolate®, MyProtein THG Company, United Kingdom)
- inborn metabolic disorders implying carbohydrate, lipid or protein metabolism - severe symptomatic hyponatremia in need of treatment with 3% NaCl-solution or in need of intensive/intermediate care treatment at time of inclusion
- Risk factors for osmotic demyelination syndrome: hypokalaemia (K <3,4 mmol/L), malnutrition, advanced liver disease, alcoholism.
- contraindication for lowering blood pressure
- type 1 diabetes mellitus
- uncontrolled type 2 diabetes mellitus (defined as HbA1c >8.0%)
Show all 17Show fewer
- uncontrolled hypothyroidism
- uncontrolled adrenal insufficiency
- reduction of eGFR <60 mL/min/1,73 m2 (KDIGO G3, G4 and G5) or end stage renal disease (dialysis)
- severe hepatic impairment (ALAT/ASAT >3x upper limit) or advanced symptomatic liver disease defined as past or current hepatic encephalopathy, liver cirrhosis Child C or decompensated (bleeding, jaundice, hepatorenal syndrome).
- treatment with a diuretic, a SGLT2 inhibitor or a corresponding combined preparation, lithium chloride, urea, vaptans, demeclocycline in the two weeks before screening.
- severe immunosuppression defined as leucocytes <2G
- pregnancy, wish to become pregnant during study period or breastfeeding
- end of life care
- Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc.
- Current participation in another intervention study
- lack of capacity or other reason preventing from giving informed consent or following study procedures.
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Basel, Department of Endocrinology
Basel, 4031
About this study
Official title: Effect of Protein Supplementation on Plasma Sodium Levels and Urinary Urea Excretion in Patients With SIAD - a Monocentric Open- Label Proof-of-concept Study -The TREASURE Study
This study aims to investigate whether a 7-day dietary high protein supplementation of 90 grams per day increases plasma sodium levels in hyponatremic patients with chronic SIAD.
Enrolled patients will receive first dietary high protein supplementation for one week. After a wash-out phase of at least one week, the patients will receive oral urea for another week.
Read the detailed description
Hyponatremia (blood sodium <135 mmol/l) is the most frequent electrolyte and fluid disturbance with a prevalence up to 30% in hospitalized patients. The most common etiology of euvolemic hyponatremia is the syndrome of inappropriate antidiuresis (SIAD) which is also the main etiology of hyponatremia overall. Urea osmotic diuresis has been reported to cause hypernatremia in critically ill patients in intensive care unit (ICU), showing that urea can influence sodium levels. Increasing solute intake with oral urea represents a valid treatment approach to increase urine volume and solute free water clearance through osmotic diuresis and reduction of urinary sodium excretion in SIAD. In Switzerland, urea is a medical food prepared as a compounding agent by pharmacies. Endogenous proteins and dietary protein are metabolized into nitrogen which is metabolized to soluble excretable urea by the liver. Protein intake could represent an osmotic relevant source of urea. The Jone's factor of 6,25 is commonly used to convert nitrogen to protein equivalent, assuming an average nitrogen content of 16% in protein (100g protein / 6,5 = 16g nitrogen).
Urea (CH₄N₂O) contains 46,6% nitrogen (atomic weight of nitrogen = 14 g/mol, atomic weight of urea = 60,1 g/mol). Using these ratios, 30g urea would correspond to 14g nitrogen and 87,5g protein. In this study, a 90g protein supplementation will be used, which corresponds roughly to 30g urea, in form of a daily intake of protein powder (Whey Protein®, foodspring GmbH, Germany or Clear Whey Isolate®, MyProtein THG Company, United Kingdom), which is freely marketed as food in Switzerland. Both interventional products are not considered as drugs.
Patients with a plasma sodium concentration <125 mmol/L are at increased risk for overcorrection, i.e., an increase in plasma sodium levels >10 mmol/L in the first 24 hours of treatment. An additional visit will be planned on the second day of treatment in order to recognize rise over this limit and initiate relowering counteractions, which will include the skip of the second powder intake and oral fluid intake.
This study is to analyze whether protein supplementation can increase plasma sodium levels in patients with SIAD by increasing urinary urea excretion.
- Being tested
- Protein supplementation, Oral urea
- Keywords
- protein supplementation, plasma sodium level, hyponatremia, urea
- Medical subject headings
- Inappropriate ADH Syndrome, Hyponatremia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Protein supplementationDietary supplement
Patients will receive a box with 7 sealable of 90-gram protein containers that will be dissolved in maximal 1L liquid (i.e., water or milk) that should be integrated in the usual daily hydration volume documented at baseline and taken daily for the following 7 days, while keeping their usual meal composition and usual fluid intake. A wash-out period of minimum 7 days between Protein supplementation and Oral urea will be performed.
Oral ureaDietary supplement
Patients will receive a box with 7 30-grams urea sealable containers. The total daily oral urea dosage of 30 grams that will be dissolved in maximal 1L of a liquid of choice (water, milk, juice, …) that should be integrated in the usual daily hydration volume documented at baseline and taken daily for the following 7 days, while keeping their usual meal composition and usual fluid intake.
| Study group | Role | What they receive |
|---|---|---|
| single arm: Phase 1: protein supplementation, Phase 2: Urea | Other | Not described Receives: Dietary Supplement: Protein supplementation; Dietary Supplement: Oral urea |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in plasma sodium concentration, (mmol/l)
The change of blood sodium during protein supplementation regimen will be visualized by means of line plots and boxplots for patients with chronic SIAD.
Measured: from baseline to 7 days after protein supplementation (7 days)
Secondary outcomes (19)
Change in estimated glomerular filtration rate (eGFR), (ml/min/1,73m2)
Change in estimated glomerular filtration rate (eGFR)
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in blood and urine osmolality, (mOsm/kg)
Change in blood and urine osmolality
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in blood and urine potassium, (mmol/L)
Change in blood and urine potassium
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in blood and urine creatinine, (umol/L)
Change in blood and urine creatinine
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in blood and urine urea, (mmol/L)
Change in blood and urine urea,
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in blood and urine uric acid, (umol/L)
Change in blood and urine uric acid
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in blood and urine glucose, (mmol/L)
Change in blood and urine glucose
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in copeptin, (pmol/l)
Change in copeptin
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in aldosterone, (pmol/l)
Change in aldosterone
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in renin, (mIU/L)
Change in renin
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in MR-proANP, (pmol/l)
Change in MR-proANP
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in NT-proBNP, (pmol/L)
Change in NT-proBNP
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in oral daily fluid intake, (ml)
Change in oral daily fluid intake assessed by a self-completed drinking protocol
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in body weight, (kg)
Change in body weight (kg)
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in both systolic and diastolic blood pressure, (mmHg)
Change in both systolic and diastolic blood pressure (mmHg)
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in heart rate, (beats/minute)
Change in heart rate (beats/minute)
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Change in general well-being measured by visual analogue scale (VAS, 0-10)
Change in general well-being measured by visual analogue scale (VAS, 0-10), with a range from 0 "worst well-being" to 10 "excellent well-being".
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Number of signs of hyponatremia (vertigo, headache, nausea, attention deficit, mental slowness, forgetfulness, gait instability) assessed by a questionnaire (yes/no)
number of signs of hyponatremia (vertigo, headache, nausea, attention deficit, mental slowness, forgetfulness, gait instability) assessed by a questionnaire (yes/no)
Measured: from baseline to 7 days after urea supplementation (up to 21 days)
Short-term change in plasma sodium level (mmol/L)
Short-term change in plasma sodium levels in patients with a plasma sodium concentration <125 mmol/L at baseline.
Measured: at day 1 (after treatment start)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2021
- Study start8 Oct 2021
- Primary completion20 Feb 2023
- Study completion20 Feb 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Syndrome of Inappropriate Antidiuresis (SIAD)Studies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- proof-of-concept study, no control group needed since patients serve as their own control in the second treatment phase
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Mirjam Christ-Crain, Prof. Dr. med., Principal investigator, Universitätsspital Basel, Endokrinologie, Diabetologie und Metabolismus
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04987385
- Sponsor's protocol ID
- 2021-01116; kt21ChristCrain2
- Acronym
- TREASURE
- Status last verified
- Feb 2023
- First submitted
- 21 Jul 2021
- Last updated
- 21 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Protein Supplementation on Plasma Sodium Levels and Urinary Urea Excretion in Patients With SIAD - a Monocentric Open- Label Proof-of-concept Study -The TREASURE Study
- ClinicalTrials.gov ID
- NCT04987385
- Acronym / sponsor ID
- TREASURE / 2021-01116; kt21ChristCrain2
- Keywords
- protein supplementation, plasma sodium level, hyponatremia, urea
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 8 Oct 2021 (actual)
- Primary completion
- 20 Feb 2023 (actual)
- Study completion
- 20 Feb 2023 (actual)
- First posted
- 3 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study aims to investigate whether a 7-day dietary high protein supplementation of 90 grams per day increases plasma sodium levels in hyponatremic patients with chronic SIAD.
Enrolled patients will receive first dietary high protein supplementation for one week. After a wash-out phase of at least one week, the patients will receive oral urea for another week.
Detailed description
Hyponatremia (blood sodium <135 mmol/l) is the most frequent electrolyte and fluid disturbance with a prevalence up to 30% in hospitalized patients. The most common etiology of euvolemic hyponatremia is the syndrome of inappropriate antidiuresis (SIAD) which is also the main etiology of hyponatremia overall. Urea osmotic diuresis has been reported to cause hypernatremia in critically ill patients in intensive care unit (ICU), showing that urea can influence sodium levels. Increasing solute intake with oral urea represents a valid treatment approach to increase urine volume and solute free water clearance through osmotic diuresis and reduction of urinary sodium excretion in SIAD. In Switzerland, urea is a medical food prepared as a compounding agent by pharmacies. Endogenous proteins and dietary protein are metabolized into nitrogen which is metabolized to soluble excretable urea by the liver. Protein intake could represent an osmotic relevant source of urea. The Jone's factor of 6,25 is commonly used to convert nitrogen to protein equivalent, assuming an average nitrogen content of 16% in protein (100g protein / 6,5 = 16g nitrogen).
Urea (CH₄N₂O) contains 46,6% nitrogen (atomic weight of nitrogen = 14 g/mol, atomic weight of urea = 60,1 g/mol). Using these ratios, 30g urea would correspond to 14g nitrogen and 87,5g protein. In this study, a 90g protein supplementation will be used, which corresponds roughly to 30g urea, in form of a daily intake of protein powder (Whey Protein®, foodspring GmbH, Germany or Clear Whey Isolate®, MyProtein THG Company, United Kingdom), which is freely marketed as food in Switzerland. Both interventional products are not considered as drugs.
Patients with a plasma sodium concentration <125 mmol/L are at increased risk for overcorrection, i.e., an increase in plasma sodium levels >10 mmol/L in the first 24 hours of treatment. An additional visit will be planned on the second day of treatment in order to recognize rise over this limit and initiate relowering counteractions, which will include the skip of the second powder intake and oral fluid intake.
This study is to analyze whether protein supplementation can increase plasma sodium levels in patients with SIAD by increasing urinary urea excretion.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- proof-of-concept study, no control group needed since patients serve as their own control in the second treatment phase
| Arm | Type | Receives |
|---|---|---|
| single arm: Phase 1: protein supplementation, Phase 2: Urea | Other | Dietary Supplement: Protein supplementation, Dietary Supplement: Oral urea |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- previous documented diagnosis of chronic SIAD
- confirmed diagnosis of SIAD at screening visit defined as:
Key exclusion criteria (17 listed)
- lactose intolerance, celiac disease, milk protein allergy, soja allergy, nuts allergy or known hypersensitivity or allergy to one of the components of the protein supplementation (Whey Protein®, foodspring GmbH, Germany or Clear Whey Isolate®, MyProtein THG Company, United Kingdom)
- inborn metabolic disorders implying carbohydrate, lipid or protein metabolism - severe symptomatic hyponatremia in need of treatment with 3% NaCl-solution or in need of intensive/intermediate care treatment at time of inclusion
- Risk factors for osmotic demyelination syndrome: hypokalaemia (K <3,4 mmol/L), malnutrition, advanced liver disease, alcoholism.
- contraindication for lowering blood pressure
- type 1 diabetes mellitus
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Protein supplementationPatients will receive a box with 7 sealable of 90-gram protein containers that will be dissolved in maximal 1L liquid (i.e., water or milk) that should be integrated in the usual daily hydration volume documented at baseline and taken daily for the following 7 days, while keeping their usual meal composition and usual fluid intake. A wash-out period of minimum 7 days between Protein supplementation and Oral urea will be performed. | Dietary supplement | single arm: Phase 1: protein supplementation, Phase 2: Urea |
| Oral ureaPatients will receive a box with 7 30-grams urea sealable containers. The total daily oral urea dosage of 30 grams that will be dissolved in maximal 1L of a liquid of choice (water, milk, juice, …) that should be integrated in the usual daily hydration volume documented at baseline and taken daily for the following 7 days, while keeping their usual meal composition and usual fluid intake. | Dietary supplement | single arm: Phase 1: protein supplementation, Phase 2: Urea |
Primary outcome
Change in plasma sodium concentration, (mmol/l)
Time frame: from baseline to 7 days after protein supplementation (7 days)
The change of blood sodium during protein supplementation regimen will be visualized by means of line plots and boxplots for patients with chronic SIAD.
19 secondary outcomes
Change in estimated glomerular filtration rate (eGFR), (ml/min/1,73m2)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in blood and urine osmolality, (mOsm/kg)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in blood and urine potassium, (mmol/L)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in blood and urine creatinine, (umol/L)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in blood and urine urea, (mmol/L)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in blood and urine uric acid, (umol/L)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in blood and urine glucose, (mmol/L)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in copeptin, (pmol/l)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in aldosterone, (pmol/l)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in renin, (mIU/L)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in MR-proANP, (pmol/l)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in NT-proBNP, (pmol/L)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in oral daily fluid intake, (ml)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in body weight, (kg)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in both systolic and diastolic blood pressure, (mmHg)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in heart rate, (beats/minute)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Change in general well-being measured by visual analogue scale (VAS, 0-10)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Number of signs of hyponatremia (vertigo, headache, nausea, attention deficit, mental slowness, forgetfulness, gait instability) assessed by a questionnaire (yes/no)
Time frame: from baseline to 7 days after urea supplementation (up to 21 days)
Short-term change in plasma sodium level (mmol/L)
Time frame: at day 1 (after treatment start)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Feb 2023.
Related trials for Syndrome of Inappropriate Antidiuresis (SIAD)
Recruiting
Urea for Treatment of Hyponatremia in Patients With SIAD Unresponsive to Fluid Restriction
SIAD - Syndrome of Inappropriate Antidiuresis
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mirjam Christ-Crain, Prof. Dr. med. principal investigator
Universitätsspital Basel, Endokrinologie, Diabetologie und Metabolismus
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Protein supplementation and Oral urea in people with Syndrome of Inappropriate Antidiuresis (SIAD), run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in plasma sodium concentration, (mmol/l) (time frame: from baseline to 7 days after protein supplementation (7 days)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Feb 2023.