Apelin study misses urine-output endpoint in 15 healthy volunteers with induced antidiuresis

An October 16 Nature Communications article-in-press reports a double-blind, randomized, placebo-controlled crossover study of intravenous [Pyr1]apelin-13 in 15 healthy adults. Researchers temporarily induced a syndrome of inappropriate antidiuresis, or SIAD, to test water regulation. Neither apelin arm produced a clinically relevant improvement in the primary urine-output endpoint compared with placebo.

The study took place at University Hospital Basel and included seven women and eight men, with a mean age of 28. Each participant attended three visits and received both apelin regimens and placebo in randomized order, separated by washout periods. This was a closely monitored experimental model in generally young, healthy volunteers, not a treatment trial in people with naturally occurring SIAD or complex medical conditions.

The primary endpoint was total urine output during the four hours from infusion start. Mean output was 173 milliliters with placebo, 156 with one apelin regimen and 158 with the other. Estimated differences from placebo were about minus 11 milliliters for each regimen, with confidence intervals spanning no difference. Because the primary null hypothesis was not rejected at the planned interim analysis, a proposed second part enrolling five patients with true SIAD was not pursued.

The higher-exposure apelin arm showed a rise in plasma sodium, but this does not turn the primary result into a positive urine-output finding. Sodium was a secondary outcome; analyses extending across the full nine-hour observation period and comparisons by sex were post hoc. Secondary confidence intervals and P values were not adjusted for multiple comparisons. These results can inform further research, not establish a proven treatment for SIAD.

The authors describe the interventions as generally well tolerated, with headache and thirst the most frequent and intense symptoms. They did not associate an adverse effect with apelin in this experiment. A sample of 15 and brief monitoring cannot establish long-term safety or rule out uncommon harms. The induced condition, strong desmopressin effect and measurement limitations also restrict translation to patients.

The study was registered as NCT06277336 and supported by Swiss academic institutions and the Swiss National Science Foundation; the paper declares no competing interests. Its findings concern this specific intravenously studied peptide and experimental model, not apelin products marketed elsewhere or other peptides. The report is not a marketing-approval notice or a reason to change clinician-directed care. No administration, dosing or buying instructions are provided.