SIAD - Syndrome of Inappropriate AntidiuresisESCAPENCT06277336
Effects of Intravenous [Pyr1]Apelin-13 on Healthy Volunteers With Artificially Induced SIAD
A study testing Apelin Low Dose, Apelin High Dose and Selected Apelin Dose in people with SIAD - Syndrome of Inappropriate Antidiuresis and Hyponatremia, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
Hyponatremia is a common electrolyte imbalance which often results from hormonal disregulation. The study aims to investigate whether the apelin hormone, which plays a role in regulating salt and water balance in the body, can be used to treat hyponatremia. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- SIAD - Syndrome of Inappropriate Antidiuresis, Hyponatremia
- What is being tested?
- Apelin Low Dose, Apelin High Dose and Selected Apelin Dose
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Mar 2024to 18 Mar 2025
- 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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Informed consent as documented by signature
- Age 18 to 65 years
- Serum sodium level 135-145mmol/l
- Clinically euvolemic status
- For female only: Due to the influence of estrogen on apelin levels, only females with combined (=containing estrogen) oral contraceptive pill will be included in order to guarantee a similar estrogen levels at each visit.
- Age ≥ 18 years
Show all 13Show fewer
- Previous documented diagnosis of chronic SIAD
- Confirmed diagnosis of SIAD at screening visit defined as:
- Plasma sodium concentration < 135 mmol/L (indirect measurement 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
- Known or suspected allergy to trial product or related products or history of multiple and/or severe allergic reaction to drugs (including study drugs) or food
- Pregnancy, wish to become pregnant during study period or breastfeeding
- Overt cardiovascular disease or abnormality in screening ECG
- Family history of sudden cardiac death or unexplained sudden death < 50 years
- Known genetic predisposition to cancer (e.g., BRCA, MEN, Lynch syndrome) or personal history/active malignant disease
- Hepatic impairment (ALAT/ASAT >3x upper limit) or liver cirrhosis
Show all 37Show fewer
- Kidney disease (GFR < 60ml/min)
- History of epileptic seizures
- Diabetes mellitus type 1 or 2
- Other severe disease requiring regular medication intake or regular medical care
- Any daily medication (including vitamin supplements).
- Uncontrolled hypertension (systolic blood pressure >160mmHg or diastolic blood pressure >100 mmHg)
- BMI <18 or >29kg/m2
- Inability to follow the procedures of the study (e.g. due to language problems, psychological disorders, dementia).
- Participation in another study with an investigational drug within the 30 days preceding and during the present study.
- Chronic SIAD patients:
- Known or suspected allergy to trial product or related products or history of multiple and/or severe allergic reaction to drugs (including study drugs) or food.
- Pregnancy, wish to become pregnant during study period or breastfeeding
- Overt cardiovascular disease or abnormality in screening ECG
- Other potential endocrine cause of hyponatraemia:
- Untreated glucocorticoid deficiency (Defined as morning serum cortisol levels < 300 nmol/l or serum cortisol levels < 450 nmol/l after synacthen test, in context of compatible clinical examination and medical history)
- Untreated severe hypothyroidism (TSH > 20 mIU/L and/or free T4 < 6 pmol/L)
- Family history of sudden cardiac death or unexplained sudden death < 50 years
- Known genetic predisposition to cancer (e.g., BRCA, MEN, Lynch syndrome, …) or personal history/active malignant disease
- Hepatic impairment (ALAT/ASAT > 3x upper limit) or liver cirrhosis
- Kidney disease (GFR < 60ml/min)
- History of epileptic seizures
- Diabetes mellitus type 1 or 2
- Severe immunosuppression defined as leukocytes < 2G
- End of life care
- 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: hypokalemia (K < 3,4 mmol/L), malnutrition, advanced liver disease, alcoholism.
- Treatment with a diuretic, a SGLT2 inhibitor or a corresponding combined preparation, lithium chloride, urea, vaptans, demeclocycline or NSAIDS in the 7 days before screening (aspirin may be continued).
- Uncontrolled hypertension (systolic blood pressure > 160mmHg or diastolic blood pressure > 100 mmHg)
- BMI < 18 or > 29kg/m2
- Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant
- Participation in another study with investigational drug within the 30 days preceding and during the present study
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effects of Intravenous [Pyr1]Apelin-13 on Healthy Volunteers With Artificially Induced SIAD- the ESCAPE Study
Hyponatremia is a common electrolyte imbalance which often results from hormonal disregulation. The study aims to investigate whether the apelin hormone, which plays a role in regulating salt and water balance in the body, can be used to treat hyponatremia.
The study will involve healthy volunteers who will be given a medication that causes their bodies to retain water, thus inducing a temporary hyponatremia state. The researchers will measure the volunteers' blood and urine electrolyte levels to see how these are influenced by apelin administration. As comparison, the same measurements will be done in volunteers dosed with placebo instead of apelin.
Read more
The researchers believe that apelin may be able to help to correct hyponatremia by increasing urine output. If the study focused in the healthy volunteers population is successful, the investigators will assess the effect of apelin administration in patients with chronic hyponatremia.
The study's hypothesis is that intravenous apelin will increase urinary excretion and sodium levels in healthy participants with artificially induced hyponatremia.
Read the detailed description
Hyponatremia (defined as plasma sodium levels <135 mmol/l) is the most frequent electrolyte and fluid disturbance with a prevalence up to 30% in hospitalized patients. It is usually classified according to its duration, its biochemical findings (hypotonic/isotonic/hypertonic, mild/moderate/profound), its symptoms severity (mild/moderate/severe) and volume status (hypovolemic/euvolemic/hypervolemic). Chronic hyponatremia (defined as a duration > 48 hours) is associated with longer hospital stays and higher hospital costs, increased mortality and morbidity, such as gait instability, falls, osteoporosis, fractures and attention deficit. Hyponatremia is recognized as a marker of poor prognosis in multiple diseases, but the extent of its causative role has not been quantified to date. There is increasing evidence that correcting hyponatremia could improve clinical outcome.
The most common etiology of euvolemic hyponatremia is the syndrome of inappropriate antidiuresis (SIAD) which is also the main etiology of hyponatremia overall. SIAD is characterized by an imbalanced arginine vasopressin (AVP) secretion or an increased renal AVP sensitivity. This leads to free water retention, thereupon to extracellular volume expansion and a subsequent renal sodium loss resulting in hypotonic hyponatremia. Patients with SIAD are usually older adults with many comorbidities and polypharmacy making physiological studies difficult to interpret due to many possible confounders. To overcome this limitation, the investigators designed a protocol of artificial SIAD induction in healthy volunteers through administration of desmopressin and water loading.This model allowed us to develop the use of the SGLT2 inhibitors empagliflozin as a promising treatment option for SIAD.
The apelin receptor is a g-protein coupled receptor whose structure resembles the angiotensin 2 type 1 receptor. It has two endogenous ligands apelin and elabela, whose different isoforms are present in different organs and are thought to work in an autocrine/paracrine manner. Apelin is, inter alia, expressed in the magnocellular neurons of the hypothalamic supraoptic and paraventricular nuclei together with AVP and oxytocin.
Apelin has a broad spectrum of beneficial physiological effects and thus represents an attractive new target in many medical fields. For instance, it naturally displays vasodilatatory and inotropic effects and promotes glucose uptake and lipolysis. In salt and water homeostasis, apelin counteracts the effects of AVP by inhibiting central AVP release and AVP renal effect, as well as by antagonizing the vasoconstrictive effects of angiotensin II on renal afferent arterioles and increasing renal blood flow.
AVP and apelin have been shown to change in opposite directions upon hypo- and hyperosmotic challenges in healthy humans. A cross-sectional study in hyponatremic patients with SIAD or heart failure suggests that not only an increased copeptin (surrogate stoichiometric marker of AVP) but also relative insufficient apelin levels contribute to renal water reabsorption in hyponatremia. Re-establishing a physiological copeptin apelin ratio by administering exogenous apelin could therefore restore a normal salt and water balance. This concept was tested in hyponatremic rats in which an apelin-17 analog increased urine output, decreased urine osmolality and increased sodium levels to a similar extent as tolvaptan. These results suggest that apelin could become an effective treatment for SIAD, once a long-acting analog will be developed for human use. However, whether a similar effect could be induced in humans is still not known and needs to be investigated in order to characterize apelin physiology in disorders of salt and water balance.
The investigators therefore hypothesize, that the administration of intravenous [Pyr1]apelin-13, the most common apelin isoform in the blood, increases urinary excretion and thus sodium levels in healthy participants with artificially induced SIAD. In case the hypothesis is confirmed, the investigators aim to investigate the physiological effect of intravenous [Pyr1]apelin-13 administration in hyponatremic patients with chronic SIAD.
- Being tested
- Placebo, Apelin Low Dose, Apelin High Dose, Selected Apelin Dose
- Keywords
- Apelin
- 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.
PlaceboDrug
Artificial SIAD induction:
- Oral water intake of 30ml/kg body weight in one hour (timepoint -2 to timepoint -1)
- Intravenous bolus of desmopressin 4 μg i.v. (Minirin®, Ferring AG) (timepoint -1)
- 300ml NaCl 0.45% (B. Braun Medical AG) over 1 hour (timepoint -1 to 0)
Study infusion (timepoint 0 to timepoint +3):
- 180-ml NaCl 0.45% infusion (placebo) over 3 hours (60ml per h)
Apelin Low DoseDrug
Artificial SIAD induction:
- Oral water intake of 30ml/kg body weight in one hour (timepoint -2 to timepoint -1)
- Intravenous bolus of desmopressin 4 μg i.v. (Minirin®, Ferring AG) (timepoint -1)
- 300ml NaCl 0.45% (B. Braun Medical AG) over 1 hour (timepoint -1 to 0)
Study infusion (timepoint 0 to timepoint +3):
- 180-ml infusion of [Pyr1]apelin-13 in NaCl 0.45% over 3 hours at an infusion rate of 1 nmol/min (60ml per h)
Apelin High DoseDrug
Artificial SIAD induction:
- Oral water intake of 30ml/kg body weight in one hour (timepoint -2 to timepoint -1)
- Intravenous bolus of desmopressin 4 μg i.v. (Minirin®, Ferring AG) (timepoint -1)
- 300ml NaCl 0.45% (B. Braun Medical AG) over 1 hour (timepoint -1 to 0)
Study infusion (timepoint 0 to timepoint +3):
- 180-ml infusion of [Pyr1]apelin-13 in NaCl 0.45% over 3 hours at an infusion rate of 10 nmol/min (60ml per h)
Selected Apelin DoseDrug
Study infusions (timepoint 0 to timepoint +3):
- 180-ml NaCl 0.45% infusion (placebo) over 3 hours (60ml per h)
- 180-ml infusion of [Pyr1]apelin-13 in NaCl 0.45% over 3 hours based on the best performing apelin dose (from Low Dose or High Dose) in healthy volunteers corresponding to one of the following options:
- at an infusion rate of 1 nmol/min (60ml per h) OR
- at an infusion rate of 10 nmol/min (60ml per h)
In case both apelin dosis performed equally well in the healthy volunteers population the lower dose will be selected.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Volunteers Intervention Order: Placebo, Apelin Low Dose, Apelin High Dose | Experimental | The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions.
Artificial SIAD induction (water loading and desmopressin administration) is performed. Receives: Drug: Placebo; Drug: Apelin Low Dose; Drug: Apelin High Dose |
| Healthy Volunteers Healthy Patients Intervention Order: Apelin Low Dose, Apelin High Dose, Placebo | Experimental | The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions.
Artificial SIAD induction (water loading and desmopressin administration) is performed. Receives: Drug: Placebo; Drug: Apelin Low Dose; Drug: Apelin High Dose |
| Healthy Volunteers Intervention Order: Apelin High Dose, Placebo, Apelin Low Dose | Experimental | The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions.
Artificial SIAD induction (water loading and desmopressin administration) is performed. Receives: Drug: Placebo; Drug: Apelin Low Dose; Drug: Apelin High Dose |
| Healthy Volunteers Intervention Order: Placebo, Apelin High Dose, Apelin Low Dose | Experimental | The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions.
Artificial SIAD induction (water loading and desmopressin administration) is performed. Receives: Drug: Placebo; Drug: Apelin Low Dose; Drug: Apelin High Dose |
| Healthy Volunteers Intervention Order: Apelin Low Dose, Placebo, Apelin High Dose | Experimental | The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions.
Artificial SIAD induction (water loading and desmopressin administration) is performed. Receives: Drug: Placebo; Drug: Apelin Low Dose; Drug: Apelin High Dose |
| Healthy Volunteers Intervention Order: Apelin High Dose, Apelin Low Dose, Placebo | Experimental | The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions.
Artificial SIAD induction (water loading and desmopressin administration) is performed. Receives: Drug: Placebo; Drug: Apelin Low Dose; Drug: Apelin High Dose |
| Chronic SIAD Patients Intervention Order: Placebo, Selected Apelin Dose | Experimental | The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Receives: Drug: Placebo; Drug: Selected Apelin Dose |
| Chronic SIAD Patients Intervention Order: Selected Apelin Dose, Placebo | Experimental | The intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Receives: Drug: Placebo; Drug: Selected Apelin Dose |
What is being measured
The primary outcome is the main question the study is designed to answer.
Total urinary excretion (ml)
Urinary excretion, in ml, between end of water loading and one hour past study infusion completion
Measured: assessment between timepoint 0 hours and timepoint +4 hours
Secondary outcomes (6)
Hourly and total urinary excretion (ml)
Change in urine volume, in ml
Measured: assessment between timepoint -2 hours and timepoint +9 hours
Change in electrolyte free water clearance (ml/min)
Change in electrolyte free water clearance, in ml/min
Measured: assessment between timepoint -2 hours and timepoint +9 hours
Change in free water clearance (ml/min)
Change in free water clearance, in ml/min
Measured: assessment between timepoint -2 hours and timepoint +9 hours
Change in plasma osmolality (mOsm/kg)
Change in plasma osmolality, in mOsm/kg
Measured: assessment between baseline and timepoint +9 hours
Change in plasma sodium (mmol/l)
Change in plasma sodium, in mmol/l
Measured: assessment between baseline and timepoint +9 hours
Change in body weight (kg)
Change in body weight, in kg
Measured: assessment between baseline and timepoint +9 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Feb 2024
- Study start1 Mar 2024
- Primary completion18 Mar 2025
- Study completion18 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SIAD - Syndrome of Inappropriate AntidiuresisStudies 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
- Non-randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 15 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., Principal investigator, University Hospital Basel; Endocrinology, Diabetes and Metabolism
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06277336
- Sponsor's protocol ID
- 2023-01716; kt23ChristCrain3
- Other IDs
- 2023
- Acronym
- ESCAPE
- Status last verified
- Mar 2025
- First submitted
- 30 Jan 2024
- Last updated
- 30 Mar 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Intravenous [Pyr1]Apelin-13 on Healthy Volunteers With Artificially Induced SIAD- the ESCAPE Study
- ClinicalTrials.gov ID
- NCT06277336
- Acronym / sponsor ID
- ESCAPE / 2023-01716; kt23ChristCrain3
- Keywords
- Apelin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Study start
- 1 Mar 2024 (actual)
- Primary completion
- 18 Mar 2025 (actual)
- Study completion
- 18 Mar 2025 (actual)
- First posted
- 26 Feb 2024 (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.
Hyponatremia is a common electrolyte imbalance which often results from hormonal disregulation. The study aims to investigate whether the apelin hormone, which plays a role in regulating salt and water balance in the body, can be used to treat hyponatremia.
The study will involve healthy volunteers who will be given a medication that causes their bodies to retain water, thus inducing a temporary hyponatremia state. The researchers will measure the volunteers' blood and urine electrolyte levels to see how these are influenced by apelin administration. As comparison, the same measurements will be done in volunteers dosed with placebo instead of apelin.
The researchers believe that apelin may be able to help to correct hyponatremia by increasing urine output. If the study focused in the healthy volunteers population is successful, the investigators will assess the effect of apelin administration in patients with chronic hyponatremia.
The study's hypothesis is that intravenous apelin will increase urinary excretion and sodium levels in healthy participants with artificially induced hyponatremia.
Detailed description
Hyponatremia (defined as plasma sodium levels <135 mmol/l) is the most frequent electrolyte and fluid disturbance with a prevalence up to 30% in hospitalized patients. It is usually classified according to its duration, its biochemical findings (hypotonic/isotonic/hypertonic, mild/moderate/profound), its symptoms severity (mild/moderate/severe) and volume status (hypovolemic/euvolemic/hypervolemic). Chronic hyponatremia (defined as a duration > 48 hours) is associated with longer hospital stays and higher hospital costs, increased mortality and morbidity, such as gait instability, falls, osteoporosis, fractures and attention deficit. Hyponatremia is recognized as a marker of poor prognosis in multiple diseases, but the extent of its causative role has not been quantified to date. There is increasing evidence that correcting hyponatremia could improve clinical outcome.
The most common etiology of euvolemic hyponatremia is the syndrome of inappropriate antidiuresis (SIAD) which is also the main etiology of hyponatremia overall. SIAD is characterized by an imbalanced arginine vasopressin (AVP) secretion or an increased renal AVP sensitivity. This leads to free water retention, thereupon to extracellular volume expansion and a subsequent renal sodium loss resulting in hypotonic hyponatremia. Patients with SIAD are usually older adults with many comorbidities and polypharmacy making physiological studies difficult to interpret due to many possible confounders. To overcome this limitation, the investigators designed a protocol of artificial SIAD induction in healthy volunteers through administration of desmopressin and water loading.This model allowed us to develop the use of the SGLT2 inhibitors empagliflozin as a promising treatment option for SIAD.
The apelin receptor is a g-protein coupled receptor whose structure resembles the angiotensin 2 type 1 receptor. It has two endogenous ligands apelin and elabela, whose different isoforms are present in different organs and are thought to work in an autocrine/paracrine manner. Apelin is, inter alia, expressed in the magnocellular neurons of the hypothalamic supraoptic and paraventricular nuclei together with AVP and oxytocin.
Apelin has a broad spectrum of beneficial physiological effects and thus represents an attractive new target in many medical fields. For instance, it naturally displays vasodilatatory and inotropic effects and promotes glucose uptake and lipolysis. In salt and water homeostasis, apelin counteracts the effects of AVP by inhibiting central AVP release and AVP renal effect, as well as by antagonizing the vasoconstrictive effects of angiotensin II on renal afferent arterioles and increasing renal blood flow.
AVP and apelin have been shown to change in opposite directions upon hypo- and hyperosmotic challenges in healthy humans. A cross-sectional study in hyponatremic patients with SIAD or heart failure suggests that not only an increased copeptin (surrogate stoichiometric marker of AVP) but also relative insufficient apelin levels contribute to renal water reabsorption in hyponatremia. Re-establishing a physiological copeptin apelin ratio by administering exogenous apelin could therefore restore a normal salt and water balance. This concept was tested in hyponatremic rats in which an apelin-17 analog increased urine output, decreased urine osmolality and increased sodium levels to a similar extent as tolvaptan. These results suggest that apelin could become an effective treatment for SIAD, once a long-acting analog will be developed for human use. However, whether a similar effect could be induced in humans is still not known and needs to be investigated in order to characterize apelin physiology in disorders of salt and water balance.
The investigators therefore hypothesize, that the administration of intravenous [Pyr1]apelin-13, the most common apelin isoform in the blood, increases urinary excretion and thus sodium levels in healthy participants with artificially induced SIAD. In case the hypothesis is confirmed, the investigators aim to investigate the physiological effect of intravenous [Pyr1]apelin-13 administration in hyponatremic patients with chronic SIAD.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Healthy Volunteers Intervention Order: Placebo, Apelin Low Dose, Apelin High Dose | Experimental | Drug: Placebo, Drug: Apelin Low Dose, Drug: Apelin High DoseThe intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Artificial SIAD induction (water loading and desmopressin administration) is performed. |
| Healthy Volunteers Healthy Patients Intervention Order: Apelin Low Dose, Apelin High Dose, Placebo | Experimental | Drug: Placebo, Drug: Apelin Low Dose, Drug: Apelin High DoseThe intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Artificial SIAD induction (water loading and desmopressin administration) is performed. |
| Healthy Volunteers Intervention Order: Apelin High Dose, Placebo, Apelin Low Dose | Experimental | Drug: Placebo, Drug: Apelin Low Dose, Drug: Apelin High DoseThe intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Artificial SIAD induction (water loading and desmopressin administration) is performed. |
| Healthy Volunteers Intervention Order: Placebo, Apelin High Dose, Apelin Low Dose | Experimental | Drug: Placebo, Drug: Apelin Low Dose, Drug: Apelin High DoseThe intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Artificial SIAD induction (water loading and desmopressin administration) is performed. |
| Healthy Volunteers Intervention Order: Apelin Low Dose, Placebo, Apelin High Dose | Experimental | Drug: Placebo, Drug: Apelin Low Dose, Drug: Apelin High DoseThe intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Artificial SIAD induction (water loading and desmopressin administration) is performed. |
| Healthy Volunteers Intervention Order: Apelin High Dose, Apelin Low Dose, Placebo | Experimental | Drug: Placebo, Drug: Apelin Low Dose, Drug: Apelin High DoseThe intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. Artificial SIAD induction (water loading and desmopressin administration) is performed. |
| Chronic SIAD Patients Intervention Order: Placebo, Selected Apelin Dose | Experimental | Drug: Placebo, Drug: Selected Apelin DoseThe intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. |
| Chronic SIAD Patients Intervention Order: Selected Apelin Dose, Placebo | Experimental | Drug: Placebo, Drug: Selected Apelin DoseThe intervention sequence is assigned in random order. Each intervention corresponds to a visit of 11h. A wash-out period of 2 to 8 weeks is planned between interventions. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Informed consent as documented by signature
- Age 18 to 65 years
- Serum sodium level 135-145mmol/l
- Clinically euvolemic status
- For female only: Due to the influence of estrogen on apelin levels, only females with combined (=containing estrogen) oral contraceptive pill will be included in order to guarantee a similar estrogen levels at each visit.
Key exclusion criteria (37 listed)
- Known or suspected allergy to trial product or related products or history of multiple and/or severe allergic reaction to drugs (including study drugs) or food
- Pregnancy, wish to become pregnant during study period or breastfeeding
- Overt cardiovascular disease or abnormality in screening ECG
- Family history of sudden cardiac death or unexplained sudden death < 50 years
- Known genetic predisposition to cancer (e.g., BRCA, MEN, Lynch syndrome) or personal history/active malignant disease
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 |
|---|---|---|
| PlaceboArtificial SIAD induction: * Oral water intake of 30ml/kg body weight in one hour (timepoint -2 to timepoint -1) * Intravenous bolus of desmopressin 4 μg i.v. (Minirin®, Ferring AG) (timepoint -1) * 300ml NaCl 0.45% (B. Braun Medical AG) over 1 hour (timepoint -1 to 0) Study infusion (timepoint 0 to timepoint +3): * 180-ml NaCl 0.45% infusion (placebo) over 3 hours (60ml per h) | Drug | Chronic SIAD Patients Intervention Order: Placebo, Selected Apelin Dose, Chronic SIAD Patients Intervention Order: Selected Apelin Dose, Placebo, Healthy Volunteers Healthy Patients Intervention Order: Apelin Low Dose, Apelin High Dose, Placebo, Healthy Volunteers Intervention Order: Apelin High Dose, Apelin Low Dose, Placebo, Healthy Volunteers Intervention Order: Apelin High Dose, Placebo, Apelin Low Dose, Healthy Volunteers Intervention Order: Apelin Low Dose, Placebo, Apelin High Dose, Healthy Volunteers Intervention Order: Placebo, Apelin High Dose, Apelin Low Dose, Healthy Volunteers Intervention Order: Placebo, Apelin Low Dose, Apelin High Dose |
| Apelin Low DoseArtificial SIAD induction: * Oral water intake of 30ml/kg body weight in one hour (timepoint -2 to timepoint -1) * Intravenous bolus of desmopressin 4 μg i.v. (Minirin®, Ferring AG) (timepoint -1) * 300ml NaCl 0.45% (B. Braun Medical AG) over 1 hour (timepoint -1 to 0) Study infusion (timepoint 0 to timepoint +3): * 180-ml infusion of [Pyr1]apelin-13 in NaCl 0.45% over 3 hours at an infusion rate of 1 nmol/min (60ml per h) | Drug | Healthy Volunteers Healthy Patients Intervention Order: Apelin Low Dose, Apelin High Dose, Placebo, Healthy Volunteers Intervention Order: Apelin High Dose, Apelin Low Dose, Placebo, Healthy Volunteers Intervention Order: Apelin High Dose, Placebo, Apelin Low Dose, Healthy Volunteers Intervention Order: Apelin Low Dose, Placebo, Apelin High Dose, Healthy Volunteers Intervention Order: Placebo, Apelin High Dose, Apelin Low Dose, Healthy Volunteers Intervention Order: Placebo, Apelin Low Dose, Apelin High Dose |
| Apelin High DoseArtificial SIAD induction: * Oral water intake of 30ml/kg body weight in one hour (timepoint -2 to timepoint -1) * Intravenous bolus of desmopressin 4 μg i.v. (Minirin®, Ferring AG) (timepoint -1) * 300ml NaCl 0.45% (B. Braun Medical AG) over 1 hour (timepoint -1 to 0) Study infusion (timepoint 0 to timepoint +3): * 180-ml infusion of [Pyr1]apelin-13 in NaCl 0.45% over 3 hours at an infusion rate of 10 nmol/min (60ml per h) | Drug | Healthy Volunteers Healthy Patients Intervention Order: Apelin Low Dose, Apelin High Dose, Placebo, Healthy Volunteers Intervention Order: Apelin High Dose, Apelin Low Dose, Placebo, Healthy Volunteers Intervention Order: Apelin High Dose, Placebo, Apelin Low Dose, Healthy Volunteers Intervention Order: Apelin Low Dose, Placebo, Apelin High Dose, Healthy Volunteers Intervention Order: Placebo, Apelin High Dose, Apelin Low Dose, Healthy Volunteers Intervention Order: Placebo, Apelin Low Dose, Apelin High Dose |
| Selected Apelin DoseStudy infusions (timepoint 0 to timepoint +3): * 180-ml NaCl 0.45% infusion (placebo) over 3 hours (60ml per h) * 180-ml infusion of [Pyr1]apelin-13 in NaCl 0.45% over 3 hours based on the best performing apelin dose (from Low Dose or High Dose) in healthy volunteers corresponding to one of the following options: 1. at an infusion rate of 1 nmol/min (60ml per h) OR 2. at an infusion rate of 10 nmol/min (60ml per h) In case both apelin dosis performed equally well in the healthy volunteers population the lower dose will be selected. | Drug | Chronic SIAD Patients Intervention Order: Placebo, Selected Apelin Dose, Chronic SIAD Patients Intervention Order: Selected Apelin Dose, Placebo |
Primary outcome
Total urinary excretion (ml)
Time frame: assessment between timepoint 0 hours and timepoint +4 hours
Urinary excretion, in ml, between end of water loading and one hour past study infusion completion
6 secondary outcomes
Hourly and total urinary excretion (ml)
Time frame: assessment between timepoint -2 hours and timepoint +9 hours
Change in electrolyte free water clearance (ml/min)
Time frame: assessment between timepoint -2 hours and timepoint +9 hours
Change in free water clearance (ml/min)
Time frame: assessment between timepoint -2 hours and timepoint +9 hours
Change in plasma osmolality (mOsm/kg)
Time frame: assessment between baseline and timepoint +9 hours
Change in plasma sodium (mmol/l)
Time frame: assessment between baseline and timepoint +9 hours
Change in body weight (kg)
Time frame: assessment between baseline and timepoint +9 hours
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 30 Mar 2025.
- Individual participant dataSharing planned: No
Related trials for SIAD - Syndrome of Inappropriate Antidiuresis
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. principal investigator
University Hospital Basel; Endocrinology, Diabetes and Metabolism
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Apelin Low Dose, Apelin High Dose and Selected Apelin Dose in people with SIAD - Syndrome of Inappropriate Antidiuresis and Hyponatremia, 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 13 inclusion and 37 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 30 Mar 2025. 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?
Total urinary excretion (ml) (time frame: assessment between timepoint 0 hours and timepoint +4 hours). 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 30 Mar 2025; AzTrials last refreshed its copy on 8 Nov 2026.