Effects of Intranasal Oxytocin in Patients With Arginine-vasopressin Deficiency - A Pilot Study
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Enrollment
- 40
- Locations
- 2
- Primary Endpoint
- Dot-probe task - anxious behavior between low dose oxytocin and placebo
Study Overview
Brief Summary
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:
- 6 IU oxytocin - 24 IU oxytocin - placebo
- 6 IU oxytocin - placebo - 24 IU oxytocin
- 24 IU oxytocin - 6 IU oxytocin - placebo
- 24 IU oxytocin - placebo - 6 IU oxytocin
- placebo - 6 IU oxytocin - 24 IU oxytocin
- 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 Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Basic Science
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Part A Arm 1
Main visit 1: 6 IU intranasal oxytocin; Main visit 2: 24 IU intranasal oxytocin; Main visit 3: intranasal placebo
Intervention: Intranasal Oxytocin (IN-OXT) (Drug)
Part A Arm 2
Main visit 1: 6 IU intranasal oxytocin; Main visit 2: intranasal placebo; Main visit 3: 24 IU intranasal oxytocin
Intervention: Intranasal Oxytocin (IN-OXT) (Drug)
Part A Arm 3
Main visit 1: 24 IU intranasal oxytocin; Main visit 2: 6 IU intranasal oxytocin; Main visit 3: intranasal placebo
Intervention: Intranasal Oxytocin (IN-OXT) (Drug)
Part A Arm 4
Main visit 1: 24 IU intranasal oxytocin; Main visit 2: intranasal placebo; Main visit 3: 6 IU intranasal oxytocin
Intervention: Intranasal Oxytocin (IN-OXT) (Drug)
Part A Arm 5
Main visit 1: intranasal placebo; Main visit 2: 6 IU intranasal oxytocin; Main visit 3: 24 IU intranasal oxytocin
Intervention: Intranasal Oxytocin (IN-OXT) (Drug)
Part A Arm 6
Main visit 1: intranasal placebo; Main visit 2: 24 IU intranasal oxytocin; Main visit 3: 6 IU intranasal oxytocin
Intervention: Intranasal Oxytocin (IN-OXT) (Drug)
Part B Arm 1
Intranasal oxytocin 6 IU three times a day for 14 days
Intervention: Intranasal Oxytocin (IN-OXT) (Drug)
Part A Arm 2
Main visit 1: 6 IU intranasal oxytocin; Main visit 2: intranasal placebo; Main visit 3: 24 IU intranasal oxytocin
Intervention: Placebo (Drug)
Part A Arm 1
Main visit 1: 6 IU intranasal oxytocin; Main visit 2: 24 IU intranasal oxytocin; Main visit 3: intranasal placebo
Intervention: Placebo (Drug)
Part A Arm 3
Main visit 1: 24 IU intranasal oxytocin; Main visit 2: 6 IU intranasal oxytocin; Main visit 3: intranasal placebo
Intervention: Placebo (Drug)
Part A Arm 4
Main visit 1: 24 IU intranasal oxytocin; Main visit 2: intranasal placebo; Main visit 3: 6 IU intranasal oxytocin
Intervention: Placebo (Drug)
Part A Arm 5
Main visit 1: intranasal placebo; Main visit 2: 6 IU intranasal oxytocin; Main visit 3: 24 IU intranasal oxytocin
Intervention: Placebo (Drug)
Part A Arm 6
Main visit 1: intranasal placebo; Main visit 2: 24 IU intranasal oxytocin; Main visit 3: 6 IU intranasal oxytocin
Intervention: Placebo (Drug)
Part B Arm 2
Intranasal placebo three times a day for 14 days
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Dot-probe task - anxious behavior between low dose oxytocin and placebo
Time Frame: 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.
Dot-probe task - anxious behavior between low dose oxytocin and placebo
Time Frame: 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
- Socioemotional functioning - Emotion recognition task between all three interventions(40 minutes following intervention at each main visit)
- Dot-probe task - anxious behavior between all three interventions(20 minutes following intervention)
- Depressive behavior - probabilistic reward task between all three interventions(30 minutes following intervention at each main visit)
- Socioemotional functioning - Emotion recognition task between all three interventions(40 minutes following intervention at each main visit)
Investigators
Elizabeth Austen Lawson
Associate Professor of Medicine, Harvard Medical School; Director, Interdisciplinary Oxytocin Research Program, Neuroendocrine Unit, Massachusetts General Hospital
Massachusetts General Hospital