Oxytocin substitution therapy in patients with AVP deficiency (central diabetes insipidus): study protocol of a double-blind, randomised placebo-controlled trial

Introduction Arginine vasopressin (AVP) and oxytocin (OXT) are both hormones released from the posterior pituitary. While AVP primarily regulates water reabsorption in the kidneys, OXT plays a key role in socioemotional functioning.

Due to the anatomical proximity, disruptions of the AVP system leading to AVP deficiency (AVP-D) may also affect the OXT system, possibly resulting in an additional OXT deficiency. This hypothesis was recently proven by using the 3,4-methylenedioxymethamphetamine stimulation tests and identifying OXT deficiency in patients with AVP-D, linked to increased anxiety and impaired emotion recognition.

Despite these findings, OXT replacement therapy is not currently established as a treatment for AVP-D and long-term replacement therapy remains unexplored. Methods and analysis This is a randomised, double-blind, placebo-controlled, parallel-group trial enrolling adults with AVP-D.

Participants are randomised 1:1 to receive intranasal OXT (Syntocinon, 24 IU twice daily) or placebo for 28 days. The primary endpoint is a composite binary outcome defined as a clinically meaningful improvement in either trait anxiety (≥5-point reduction in State-Trait Anxiety Inventory-Trait Score) or emotion recognition (≥4-point increase in EmBody/EmFace task performance).