Effects of Intranasal Oxytocin in Patients With Arginine-vasopressin Deficiency

Effects of Intranasal Oxytocin in Patients With Arginine-vasopressin Deficiency - A Pilot Study

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.

Study Overview

• Status: Recruiting
• Conditions: Vasopressin Deficiency
• Intervention / Treatment: Drug: Intranasal Oxytocin (IN-OXT); Drug: Intranasal Oxytocin (IN-OXT); Drug: Placebo; Drug: Intranasal Oxytocin (IN-OXT); Drug: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Francesca Galbiati, MD; Phone Number: (617) 726-3870; Email: fgalbiati@bwh.harvard.edu
• Study Contact Backup: Name: Elisa Asanza, MSN, MPH; Phone Number: 617-726-3870; Email: easanza@mgh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital, Neuroendocrine Unit
      • Contact: Francesca Galbiati, MD; Phone Number: (617) 726-3870; Email: fgalbiati@bwh.harvard.edu
      • Contact: Elisa Asanza, MSN, MPH; Phone Number: 617-726-3870; Email: easanza@mgh.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 56 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age 18 and above
• Arginine-vasopressin deficiency
• Normal FT4 or T4
• 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 within 4 weeks of enrollment or planned medication changes during the study
• 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 cardiac disease, including arrhythmias, coronary heart disease, coronary artery spasms, valvular heart disease, hypertrophic cardiomyopathy (hypertension is not exclusionary)
• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part A Arm 1; Main visit 1: 6 IU intranasal oxytocin; Main visit 2: 24 IU intranasal oxytocin; Main visit 3: intranasal placebo	Drug: Intranasal Oxytocin (IN-OXT); 6 IU single dose; Drug: Intranasal Oxytocin (IN-OXT); IN-OXT 6 IU three times a day for 2 weeks; Drug: Placebo; Intranasal placebo three times a day for 2 weeks; Drug: Intranasal Oxytocin (IN-OXT); 24 IU single dose; Drug: Placebo; placebo single dose
Experimental: Part A Arm 2; Main visit 1: 6 IU intranasal oxytocin; Main visit 2: intranasal placebo; Main visit 3: 24 IU intranasal oxytocin	Drug: Intranasal Oxytocin (IN-OXT); 6 IU single dose; Drug: Intranasal Oxytocin (IN-OXT); IN-OXT 6 IU three times a day for 2 weeks; Drug: Placebo; Intranasal placebo three times a day for 2 weeks; Drug: Intranasal Oxytocin (IN-OXT); 24 IU single dose; Drug: Placebo; placebo single dose
Experimental: Part A Arm 3; Main visit 1: 24 IU intranasal oxytocin; Main visit 2: 6 IU intranasal oxytocin; Main visit 3: intranasal placebo	Drug: Intranasal Oxytocin (IN-OXT); 6 IU single dose; Drug: Intranasal Oxytocin (IN-OXT); IN-OXT 6 IU three times a day for 2 weeks; Drug: Placebo; Intranasal placebo three times a day for 2 weeks; Drug: Intranasal Oxytocin (IN-OXT); 24 IU single dose; Drug: Placebo; placebo single dose
Experimental: Part A Arm 4; Main visit 1: 24 IU intranasal oxytocin; Main visit 2: intranasal placebo; Main visit 3: 6 IU intranasal oxytocin	Drug: Intranasal Oxytocin (IN-OXT); 6 IU single dose; Drug: Intranasal Oxytocin (IN-OXT); IN-OXT 6 IU three times a day for 2 weeks; Drug: Placebo; Intranasal placebo three times a day for 2 weeks; Drug: Intranasal Oxytocin (IN-OXT); 24 IU single dose; Drug: Placebo; placebo single dose
Experimental: Part A Arm 5; Main visit 1: intranasal placebo; Main visit 2: 6 IU intranasal oxytocin; Main visit 3: 24 IU intranasal oxytocin	Drug: Intranasal Oxytocin (IN-OXT); 6 IU single dose; Drug: Intranasal Oxytocin (IN-OXT); IN-OXT 6 IU three times a day for 2 weeks; Drug: Placebo; Intranasal placebo three times a day for 2 weeks; Drug: Intranasal Oxytocin (IN-OXT); 24 IU single dose; Drug: Placebo; placebo single dose
Experimental: Part A Arm 6; Main visit 1: intranasal placebo; Main visit 2: 24 IU intranasal oxytocin; Main visit 3: 6 IU intranasal oxytocin	Drug: Intranasal Oxytocin (IN-OXT); 6 IU single dose; Drug: Intranasal Oxytocin (IN-OXT); IN-OXT 6 IU three times a day for 2 weeks; Drug: Placebo; Intranasal placebo three times a day for 2 weeks; Drug: Intranasal Oxytocin (IN-OXT); 24 IU single dose; Drug: Placebo; placebo single dose
Active Comparator: Part B Arm 1; Intranasal oxytocin 6 IU three times a day for 14 days	Drug: Intranasal Oxytocin (IN-OXT); 6 IU single dose; Drug: Intranasal Oxytocin (IN-OXT); IN-OXT 6 IU three times a day for 2 weeks; Drug: Intranasal Oxytocin (IN-OXT); 24 IU single dose
Experimental: Part B Arm 2; Intranasal placebo three times a day for 14 days	Drug: Placebo; Intranasal placebo three times a day for 2 weeks; Drug: Placebo; placebo single dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dot-probe task - anxious behavior between low dose oxytocin and placebo	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.	20 minutes following intervention at each main visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dot-probe task - anxious behavior between all three interventions	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.	20 minutes following intervention
Depressive behavior - probabilistic reward task between all three interventions	Response bias developed toward the more frequently reinforced alternative between 6 IU oxytocin, 24 IU oxytocin, and placebo in the probabilistic reward task.	30 minutes following intervention at each main visit
Socioemotional functioning - Emotion recognition task between all three interventions	Accuracy in identifying correct emotion between 6 IU oxytocin, 24 IU oxytocin, and placebo in the emotion recognition task.	40 minutes following intervention at each main visit

Collaborators and Investigators

• Sponsor: Elizabeth Austen Lawson
• Collaborators: Tonix Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Elizabeth A Lawson, MD, MMSc, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 10, 2025
• Primary Completion (Estimated): June 1, 2026
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: March 5, 2021
• First Submitted That Met QC Criteria: March 5, 2021
• First Posted (Actual): March 9, 2021

Study Record Updates

• Last Update Posted (Estimated): September 16, 2025
• Last Update Submitted That Met QC Criteria: September 10, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: oxytocin; anxiety; psychopathology; depressive symptoms; Hypopituitarism; posterior pituitary; socioemotional functioning
• Additional Relevant MeSH Terms: Urogenital Diseases; Endocrine System Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Behavioral Symptoms; Hypothalamic Diseases; Pituitary Diseases; Diabetes Insipidus; Behavior; Anxiety Disorders; Depression; Diabetes Insipidus, Neurogenic; Hypopituitarism; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: 2020P003071

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No