Intravenous [Pyr¹]apelin-13 in Healthy Volunteers with Artificially-Induced Syndrome of Inappropriate Antidiuresis - a double-blind, randomised, placebo-controlled crossover study

Apelin, a hormone secreted by the posterior pituitary, antagonises arginine vasopressin in salt and water homoeostasis. Administration of apelin analogues increased urine output in hyponatremic rodent models, but corresponding human data are lacking. We therefore investigated intravenous [Pyr¹]apelin-13 in healthy participants with artificially induced syndrome of inappropriate antidiuresis. In this double-blind, randomised, placebo-controlled crossover study, 15 healthy adults (7 female; mean age, 28 years [SD, 8]) attended three study visits. Hyponatremia was induced using desmopressin, water loading, and hypotonic saline. Participants subsequently received high-dose [Pyr¹]apelin-13 (1800 nmol), low-dose [Pyr¹]apelin-13 (180 nmol), or placebo as a 3-hour infusion. The primary endpoint was cumulative urine output from infusion initiation until 1 hour after its completion. Neither apelin dose produced a clinically relevant difference in urine output compared with placebo. ClinicalTrials.gov: NCT06277336. Funded by the Swiss National Science Foundation. Registration number: NCT06277336 .