Vasopressin Deficiency

This is a randomized, double-blind, placebo-controlled crossover pilot study of single-dose intranasal oxytocin (6 IU and 24 IU) vs. placebo in adult men and women (aged 18 years and above) with arginine-vasopressin deficiency to evaluate the effect of oxytocin on anxiety, depression, and socioemotional functioning (Part A), with an optional randomized, double-blind, placebo-controlled 2-week repeated dose substudy of intranasal oxytocin 6 IU or placebo (Part B). Following a screening visit to determine eligibility, participants will return for three main study visits in Part A. During the main study visits, study participants will receive either oxytocin or placebo, followed by assessments of emotional behavior. In Part A, thirty participants will be equally randomized to one of six possible groups: 1. 6 IU oxytocin - 24 IU oxytocin - placebo 2. 6 IU oxytocin - placebo - 24 IU oxytocin 3. 24 IU oxytocin - 6 IU oxytocin - placebo 4. 24 IU oxytocin - placebo - 6 IU oxytocin 5. placebo - 6 IU oxytocin - 24 IU oxytocin 6. placebo - 24 IU oxytocin - 6 IU oxytocin Following completion of the Part A crossover portion of the study, in Part B participants may also choose to continue participation in an optional, randomized, double-blind, placebo-controlled substudy of intranasal oxytocin 6 IU or placebo three times a day for two weeks, followed by assessments of emotional behavior.

Arginine-vasopressin (AVP) is a non-catecholaminergic hormone produced in the hypothalamus and released into the circulation via the neurohypophysis. It has different actions depending on the receptors through which it acts: V1 (vasoconstriction, platelet aggregation, efferent arteriole constriction of the renal glomerulus, glycogenolysis); V2 (water reabsorption, release of von Willebrand factor and factor VIII); V3 (increased cortisol and insulin). Septic shock is the most common cause of vasoplegic shock and its management includes control of the focus, early antibiotic therapy, volume resuscitation, vasopressor therapy, support of various organ dysfunctions, as well as monitoring and follow-up. The Surviving Sepsis Campaign (a global initiative to improve sepsis management) recommends noradrenaline as the first line of vasopressor therapy and early addition of AVP as a second line rather than further up-titration of noradrenaline when signs of hypoperfusion persist, through its action primarily on V1. The rationale for its use in septic shock would be: * endogenous vasopressin deficiency present in septic shock; * as a catecholamine-sparing strategy, reducing the side effects of catecholamines; * its potential nephroprotective effect; * its use should be early. The uncertainties surrounding the use of AVP in septic shock and other types of shock are many, hence the need for this registry.