{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T15:53:23Z","timestamp":1782489203499,"version":"3.54.5"},"reference-count":58,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T00:00:00Z","timestamp":1777852800000},"content-version":"unspecified","delay-in-days":3,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["213580"],"award-info":[{"award-number":["213580"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2026,4,13]]},"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>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\u2009IU 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 (\u22655-point reduction in State-Trait Anxiety Inventory-Trait Score) or emotion recognition (\u22654-point increase in EmBody\/EmFace task performance). Secondary outcomes include empathy, stress reactivity, neuroimaging markers of amygdala activity, additional psychological measures, metabolic parameters and safety outcomes, including hyponatraemia. Analyses will follow the intention-to-treat principle, with Fisher\u2019s exact test used for the primary outcome and mixed-effects models for secondary endpoints.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The study has been approved by the competent ethics committees and regulatory authorities in Switzerland and the European Union. The following institutions granted ethical approval: Ethikkommission Nordwest- und Zentralschweiz (EKNZ), project number EKNZ 2023\u201301010\u2009and the Erasmus MC MERC, EU-CT number 2024\u20135\u200916\u2009813-19-00. Results will be published in open-access, peer-reviewed journals and disseminated via scientific meetings, media communication and lay summaries provided to participants. De-identified individual participant data will be made available on reasonable request following publication.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06036004\">NCT06036004<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-109940","type":"journal-article","created":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T16:00:29Z","timestamp":1777910429000},"page":"e109940","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Oxytocin substitution therapy in patients with AVP deficiency (central diabetes insipidus): study protocol of a double-blind, randomised placebo-controlled trial"],"prefix":"10.1136","volume":"16","clinical-trial-number":[{"clinical-trial-number":"nct06036004","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct06036004","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Cihan","family":"Atila","sequence":"first","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, BS, Switzerland"},{"name":"Department of Clinical Research, University Hospital Basel, University of Basel, Basel, BS, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svenja","family":"Leibnitz","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, BS, Switzerland"},{"name":"Department of Clinical Research, University Hospital Basel, University of Basel, Basel, BS, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-2294-9262","authenticated-orcid":false,"given":"Andi","family":"Nikaj","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, BS, Switzerland"},{"name":"Department of Clinical Research, University Hospital Basel, University of Basel, Basel, BS, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias E","family":"Liechti","sequence":"additional","affiliation":[{"name":"Department of Clinical Research, University Hospital Basel, University of Basel, Basel, BS, Switzerland"},{"name":"Division of Clinical Pharmacology and Toxicology, Universitatsspital Basel Labormedizin, Basel, BS, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominique","family":"De Quervain","sequence":"additional","affiliation":[{"name":"Division of Cognitive Neuroscience, University of Basel, Basel, BS, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam","family":"Christ-Crain","sequence":"additional","affiliation":[{"name":"Department of Endocrinology, Diabetes and Metabolism, University Hospital Basel, Basel, BS, Switzerland"},{"name":"Department of Clinical Research, University Hospital Basel, University of Basel, Basel, BS, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2026,5,4]]},"reference":[{"key":"2026062608310916000_16.5.e109940.1","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1038\/s41574-024-00985-x","article-title":"Arginine vasopressin deficiency: diagnosis, management and the relevance of oxytocin deficiency","volume":"20","author":"Atila","year":"2024","journal-title":"Nat Rev Endocrinol"},{"key":"2026062608310916000_16.5.e109940.2","doi-asserted-by":"crossref","unstructured":"Melmed S , Polonsky KS , Larsen PR , et al . 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