Dose Response Relationship of Oxytocin on Irritability in Youths

NCT03863288 | Terminated Phase 1 DMC FDA Drug

• 2 other identifiers: 0219-20-FB1U01MH120155-01A1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study is a randomized, double-blind proof of concept (PoC) study on the neural impact of intranasal oxytocin (OXT) administration for adolescents (age 14 to 18), demonstrating a clinically significant level of irritability as defined by a score of ≥4 on the Affective Reactivity Index (ARI). Planned enrollment is 80 subjects over 3 years.

Conditions

Irritable Mood

Keywords

oxytocin; neuroimaging; irritability; fMRI; pharmacokinetics

Outcome Measures

Primary Outcomes (2)

• Blood Oxygen Level Dependent (BOLD) response within rostro-medial prefrontal cortex ( rmPFC) region of interest to emotional stimuli during the Affective Stroop (AS) at approximately 50 minutes after intranasal administration of OXT.

  Neural changes observable on fMRI as BOLD responses in medial prefrontal cortex. Response data will be generated for each participant for the four OXT doses (8, 24, 48 and 80 IU) and placebo.

  50 minutes

• Plasma concentrations of OXT at 10, 20, 30, 40, and 50 minutes post intranasal OXT administration, and immediately post-fMRI scanning.

  Area under the curve (OXT dose response)

  50 minutes and 2 hours

Secondary Outcomes (4)

• BOLD responses within the amygdala region of interest (ROI) to emotional stimuli during the Affective Stroop (AS) task (at approximately 50 minutes after intranasal administration of OXT (placebo, 8, 24, 48, and 80 IU).

  50 minutes

• The degree of functional connectivity between rmPFC and amygdala during resting-state fMRI (rs-fMRI) after intranasal administration of OXT.

  60 minutes

• BOLD responses within peri-aqueductal gray (PAG) and amygdala regions of interest (ROIs) to emotional stimuli during the facial expression task (at approximately 70 minutes) after intranasal administration of OXT.

  70 minutes

• Saliva level of OXT at 10, 20, 30, 40 and 50 minutes post-administration of intranasal OXT, and immediately after fMRI scanning to calculate area under curve (AUC)

  50 minutes and 2 hours

Study Arms (5)

Intranasal Spray Placebo

PLACEBO COMPARATOR

Nasal spray of placebo liquid solution as a single dose. fMRI scan pre and post-administration.

Procedure: Functional MRI (fMRI); Drug: Placebo

Oxytocin Intranasal Spray 8 International Unit (IU)

ACTIVE COMPARATOR

Nasal spray of Oxytocin 8 International Unit (8IU) liquid solution as a single dose. fMRI scan pre and post administration.

Procedure: Functional MRI (fMRI); Drug: Oxytocin Intranasal Spray 8 International Unit (8IU)

Oxytocin Intranasal Spray 24 International Unit (IU)

ACTIVE COMPARATOR

Nasal spray of Oxytocin 24 International Unit (24IU) liquid solution as a single dose. fMRI scan pre and post administration.

Procedure: Functional MRI (fMRI); Drug: Oxytocin intranasal spray 24 International Unit (24IU)

Oxytocin Intranasal Spray 48 International Unit (IU)

ACTIVE COMPARATOR

Nasal spray of Oxytocin 48 International Unit (48IU) liquid solution as a single dose. fMRI scan pre and post administration.

Procedure: Functional MRI (fMRI); Drug: Oxytocin intranasal spray 48 International Unit (48IU)

Oxytocin Intranasal Spray 80 International Unit (IU)

ACTIVE COMPARATOR

Nasal spray of Oxytocin 80 International Unit (80IU) liquid solution as a single dose. fMRI scan pre and post-administration.

Procedure: Functional MRI (fMRI); Drug: Oxytocin intranasal spray 80 International Unit (80IU)

Interventions

Functional MRI (fMRI) PROCEDURE

Functional MRI (fMRI) scan with affective/cognitive tasks

Intranasal Spray Placebo; Oxytocin Intranasal Spray 24 International Unit (IU); Oxytocin Intranasal Spray 48 International Unit (IU); Oxytocin Intranasal Spray 8 International Unit (IU); Oxytocin Intranasal Spray 80 International Unit (IU)

Oxytocin Intranasal Spray 8 International Unit (8IU) DRUG

Oxytocin intranasal spray liquid administration

Oxytocin Intranasal Spray 8 International Unit (IU)

Oxytocin intranasal spray 24 International Unit (24IU) DRUG

Oxytocin intranasal spray liquid administration

Oxytocin Intranasal Spray 24 International Unit (IU)

Oxytocin intranasal spray 48 International Unit (48IU) DRUG

Oxytocin intranasal spray liquid administration

Oxytocin Intranasal Spray 48 International Unit (IU)

Oxytocin intranasal spray 80 International Unit (80IU) DRUG

Oxytocin intranasal spray liquid administration

Oxytocin Intranasal Spray 80 International Unit (IU)

Placebo DRUG

Placebo intranasal spray liquid administration

Intranasal Spray Placebo

Eligibility Criteria

• Age: 14 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• years of age
• current diagnosis of Attention Deficit/Hyperactivity Disorder (ADHD), Oppositional Defiant Disorder (ODD), Conduct Disorder (CD), or Disruptive Mood Dysregulation Disorder (DMDD) as determined by the Kiddie-Schedule for Affective Disorders and Schizophrenia (K-SADS), lifetime version;54
• Clinically significant level of irritability as defined by a score of ≥4 on the Affective Reactivity Index (ARI)
• If currently on medication, treatment must be stable for at least 2 weeks with stimulant medication, and at least 4 weeks with alpha 2 agonist, atomoxetine, antipsychotics, mood stabilizers, or antidepressant.

You may not qualify if:

• Comorbid psychotic, tic, autism spectrum disorder, or substance use disorders, or current diagnosis of bipolar disorder; -Major medical illness that prohibits OXT administration (e.g., severe liver disease, seizure disorder, metabolic disorder)
• Past history of allergic reaction to OXT and its intranasal product
• History of Central Nervous System (CNS) disease (including history of seizure, epilepsy, CNS tumor, CNS hemorrhage, or serious CNS infection including meningitis or encephalitis)
• A positive urine pregnancy test
• A positive urine drug screen or currently active diagnosis of substance use disorder
• Wechsler Abbreviated Scale of Intelligence (WASI-2; two subset form) scores \<70
• Metal in the body (i.e., hearing aid, cardiac pacemaker, bone plates, braces, non-removable piercing/implants, etc.), claustrophobia, or any other condition that would preclude MRI scanning.

Sponsors & Collaborators

• University of Nebraska: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of Nebraska Medical Center, Department of Psychiatry

Omaha, Nebraska, 61898-5581, United States

Location

Related Publications (24)

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Study Officials

• Soonjo Hwang, MD

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Subjects are randomly assigned to one of 4 doses of OXT or placebo. Investigators and subjects and parents/guardians are blinded to assignment.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized, double-blind, placebo-controlled

Study Record Dates

• First Submitted: September 25, 2018
• First Posted: March 5, 2019
• Study Start: February 18, 2022
• Primary Completion: February 27, 2024
• Study Completion: February 27, 2024
• Last Updated: March 14, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)