Effects of Intravenous [Pyr1]Apelin-13 on Healthy Volunteers With Artificially Induced SIAD
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.
- EligibilityCriteria: Healthy Volunteers:  Inclusion Criteria:  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.  Exclusion Criteria:  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 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:  Inclusion Criteria:  Age ≥ 18 years 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)  Exclusion Criteria:  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 - HealthyVolunteers: Accepts Healthy Volunteers - Gender: All - MinimumAge: 18 Years - MaximumAge: 65 Years - StdAgeList: Adult, Older Adult