Intravenous [Pyr¹]apelin-13 in Healthy Volunteers with Artificially-Induced Syndrome of Inappropriate Antidiuresis - a double-blind, randomised, placebo-controlled crossover study
Abstract
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 .
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BibTeX
@article{monnerat2026intravenous,
title = {{Intravenous [Pyr¹]apelin-13 in Healthy Volunteers with Artificially-Induced Syndrome of Inappropriate Antidiuresis - a double-blind, randomised, placebo-controlled crossover study}},
author = {Sophie Monnerat and Sven Lustenberger and Chiara A. Bizzozero and Fiona A. Chapman and Joyce Santos de Jesus and Eszter Kustos-Toth and Deborah R. Vogt and Lorraine Bruce and Robert Little and Anthony P. Davenport and Janet J. Maguire and Julie Refardt and Martin Bidlingmaier and Neeraj Dhaun and Mirjam Christ-Crain},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78333-y},
url = {https://www.nature.com/articles/s41467-026-78333-y},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Intravenous [Pyr¹]apelin-13 in Healthy Volunteers with Artificially-Induced Syndrome of Inappropriate Antidiuresis - a double-blind, randomised, placebo-controlled crossover study
AU - Sophie Monnerat
AU - Sven Lustenberger
AU - Chiara A. Bizzozero
AU - Fiona A. Chapman
AU - Joyce Santos de Jesus
AU - Eszter Kustos-Toth
AU - Deborah R. Vogt
AU - Lorraine Bruce
AU - Robert Little
AU - Anthony P. Davenport
AU - Janet J. Maguire
AU - Julie Refardt
AU - Martin Bidlingmaier
AU - Neeraj Dhaun
AU - Mirjam Christ-Crain
PY - 2026
DA - 2026/10/16
JO - Nature Communications
DO - 10.1038/s41467-026-78333-y
UR - https://www.nature.com/articles/s41467-026-78333-y
AB - 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 .
SN - 2041-1723
ER -