Effects of Intranasal Oxytocin in Patients With Arginine-vasopressin Deficiency

• Intranasal Oxytocin (IN-OXT) 6 IU single dose (Drug): Part A: 6 IU single dose
• Intranasal Oxytocin (IN-OXT) 6 IU repeat dose (Drug): Part B: IN-OXT 6 IU three times a day for 2 weeks
• Placebo repeat dose (Drug): Part B: Intranasal placebo three times a day for 2 weeks
• Intranasal Oxytocin (IN-OXT) 24 IU single dose (Drug): Part A: 24 IU single dose
• Placebo single dose (Drug): Part A: placebo single dose

Primary outcomes

• Dot-probe task - anxious behavior between low dose oxytocin and placebo [20 minutes following intervention at each main visit]: Difference in response times (in milliseconds) to dots appearing in the location of the previously shown negative versus the neutral face between 6 IU oxytocin vs placebo in the dot-probe task.

Secondary outcomes

• Dot-probe task - anxious behavior between all three interventions [20 minutes following intervention]: Difference in response time (in milliseconds) to dots appearing in the location of the previously shown negative versus neutral face between 6 IU oxytocin, 24 IU oxytocin, and placebo in the dot-probe task.
• Depressive behavior - probabilistic reward task between all three interventions [30 minutes following intervention at each main visit]: Response bias developed toward the more frequently reinforced alternative between 6 IU oxytocin, 24 IU oxytocin, and placebo in the probabilistic reward task.
• Socioemotional functioning - Emotion recognition task between all three interventions [40 minutes following intervention at each main visit]: Accuracy in identifying correct emotion between 6 IU oxytocin, 24 IU oxytocin, and placebo in the emotion recognition task.

Sex: All, ages: 18 Years to any

Inclusion Criteria:

* Age 18 and above
* Arginine-vasopressin deficiency
* Normal FT4
* Normal serum/plasma sodium
* Stable hormone replacement

Exclusion Criteria:

* Active substance use disorder within the last 6 months
* History of psychosis
* Suicidal behavior and/or active suicidal ideation with plan and/or intent, e.g., suicidal ideation of type 4 or type 5 as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS), in the last month
* Medication changes that could interfere with study procedures or endpoints per study physician discretion
* History of chronic nasal obstruction or local pathology in nostril pathway which, in the opinion of the investigator, would prevent appropriate nasal administration of the study drug.
* History of clinically relevant ventricular arrhythmias, coronary heart disease, and hypertrophic cardiomyopathy
* History of chronic kidney disease stage III and above
* History of liver cirrhosis
* Pregnancy or breastfeeding within the last 8 weeks
* Unwilling to use a medically acceptable form of contraception throughout the study period (female of child-bearing potential only)
* Any significant illness, condition, drug or medical device that the Investigator determines could interfere with study participation, data collection, or safety

• Elizabeth A Lawson, MD, MMSc, Principal investigator, Massachusetts General Hospital