escAPe study

Switzerland (ICTRP)

ID di studio ICTRP
NCT06277336 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
Effects of Intravenous [Pyr1]apelin-13 in Healthy Volunteers with Artificially Induced SIAD and Patients with SIAD – a monocentric randomized double-blind placebo-controlled cross-over study - the escAPe Study (BASEC)

Titolo accademico
Effects of Intravenous [Pyr1]Apelin-13 on Healthy Volunteers With Artificially Induced SIAD- the ESCAPE Study (ICTRP)

Titolo pubblico
Effects of Intravenous [Pyr1]Apelin-13 on Healthy Volunteers With Artificially Induced SIAD (ICTRP)

Malattie studiate
SIAD - Syndrome of Inappropriate AntidiuresisHyponatremia (ICTRP)

Intervento studiato
Drug: PlaceboDrug: Apelin Low DoseDrug: Apelin High DoseDrug: Selected Apelin Dose (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: Non-Randomized. Intervention model: Crossover Assignment. Primary purpose: Treatment. Masking: Double (Participant, Care Provider). (ICTRP)

Criteri di inclusione/esclusione
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 (ICTRP)

non disponibile

Endpoint primari e secondari
Total urinary excretion (ml) (ICTRP)

Hourly and total urinary excretion (ml);Change in electrolyte free water clearance (ml/min);Change in free water clearance (ml/min);Change in plasma osmolality (mOsm/kg);Change in plasma sodium (mmol/l);Change in body weight (kg) (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
non disponibile

Contatti aggiuntivi
Mirjam Christ-Crain, Prof. Dr.;Sven Lustenberger, MD.;Mirjam Christ-Crain, Prof. Dr., sven.lustenberger@usb.ch; Mirjam.Christ-Crain@usb.ch, +41 61 328 62 64;+41 61 328 70 80, University Hospital Basel, Endocrinology, Diabetes and Metabolism, (ICTRP)

ID secondari
2023-01716, kt23ChristCrain3 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT06277336 (ICTRP)