Dose Response Relationship of Oxytocin on Irritability in Youths

NCT ID: NCT03863288

Last Updated: 2025-03-14

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-02-18
• Study Completion Date: 2024-02-27

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.

Detailed Description

Endogenous oxytocin (OXT) has been a focus of prior psychiatric research due to its role in pro-social behavior, and modulation of response to social/emotional stimuli. Although many studies argue that the intranasal administration of OXT can produce behavioral as well as neural changes, there is surprisingly little comprehensive research on this issue. Most of the previous studies are limited by using a single dose of intranasal OXT in small samples, and there is no current consensus regarding appropriate dosage and very little data on neural impact as a function of dose. There has been little consideration of the relation between pharmacokinetics (peripheral level of OXT after administration) and the degree of induced neural changes. None of these issues have been studied in a pediatric population with clinically significant psychopathology. This study is proposed to determine the extent to which neural changes are induced by OXT intranasal administration, by examining the dose-response relationship (the degree of neural changes induced by various doses of OXT) and the correlation of pharmacokinetics (peripheral level of OXT after administration and the induced neural changes) in youths with clinically significant psychopathology. The form of psychopathology targeted is irritability: the increased propensity to exhibit anger relative to peers.One of the neurobiological mechanisms of irritability implicates dysfunction in the acute threat response system. OXT, with its most commonly proposed mechanism being reduction of hyperactivity in the acute threat response system, is a potentially promising agent to induce neural changes in the target brain areas of the acute threat response system for youths with high levels of irritability. The study aims to quantify the extent to which different doses of OXT will reduce the activation of the acute threat response system to emotional stimuli in youths with high levels of irritability. Both resting state and task-based functional MRI will be used , using affective-cognitive tasks (to obtain the primary aim will begin after the clinician scan) with demonstrated test-retest reliability and capability of capturing the core target areas of OXT administration in the acute threat response system. Pharmacokinetics (plasma and saliva level) after OXT administration will be examined to determine correlation with the induced neural changes in the target areas.

Conditions

Irritable Mood

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Intranasal Spray Placebo

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

Group Type: PLACEBO_COMPARATOR

Functional MRI (fMRI)

Intervention Type: PROCEDURE

Functional MRI (fMRI) scan with affective/cognitive tasks

Placebo

Intervention Type: DRUG

Placebo intranasal spray liquid administration

Oxytocin Intranasal Spray 8 International Unit (IU)

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

Group Type: ACTIVE_COMPARATOR

Functional MRI (fMRI)

Intervention Type: PROCEDURE

Functional MRI (fMRI) scan with affective/cognitive tasks

Oxytocin Intranasal Spray 8 International Unit (8IU)

Intervention Type: DRUG

Oxytocin intranasal spray liquid administration

Oxytocin Intranasal Spray 24 International Unit (IU)

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

Group Type: ACTIVE_COMPARATOR

Functional MRI (fMRI)

Intervention Type: PROCEDURE

Functional MRI (fMRI) scan with affective/cognitive tasks

Oxytocin intranasal spray 24 International Unit (24IU)

Intervention Type: DRUG

Oxytocin intranasal spray liquid administration

Oxytocin Intranasal Spray 48 International Unit (IU)

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

Group Type: ACTIVE_COMPARATOR

Functional MRI (fMRI)

Intervention Type: PROCEDURE

Functional MRI (fMRI) scan with affective/cognitive tasks

Oxytocin intranasal spray 48 International Unit (48IU)

Intervention Type: DRUG

Oxytocin intranasal spray liquid administration

Oxytocin Intranasal Spray 80 International Unit (IU)

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

Group Type: ACTIVE_COMPARATOR

Functional MRI (fMRI)

Intervention Type: PROCEDURE

Functional MRI (fMRI) scan with affective/cognitive tasks

Oxytocin intranasal spray 80 International Unit (80IU)

Intervention Type: DRUG

Oxytocin intranasal spray liquid administration

Interventions

Functional MRI (fMRI)

Functional MRI (fMRI) scan with affective/cognitive tasks

Intervention Type: PROCEDURE

Oxytocin Intranasal Spray 8 International Unit (8IU)

Oxytocin intranasal spray liquid administration

Intervention Type: DRUG

Oxytocin intranasal spray 24 International Unit (24IU)

Oxytocin intranasal spray liquid administration

Intervention Type: DRUG

Oxytocin intranasal spray 48 International Unit (48IU)

Oxytocin intranasal spray liquid administration

Intervention Type: DRUG

Oxytocin intranasal spray 80 International Unit (80IU)

Oxytocin intranasal spray liquid administration

Intervention Type: DRUG

Placebo

Placebo intranasal spray liquid administration

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 14-18 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 14 Years
• Maximum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: collaborator

University of Nebraska

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Soonjo Hwang, MD

Role: PRINCIPAL_INVESTIGATOR

University of Nebraska

Locations

University of Nebraska Medical Center, Department of Psychiatry

Omaha, Nebraska, United States

Countries

United States

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Other Identifiers

1U01MH120155-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

0219-20-FB

Identifier Type: -

Identifier Source: org_study_id