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Oxytocin on Irritability/Emotional Dysregulation of Disruptive Behavior and Mood Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02824627
Recruitment Status : Recruiting
First Posted : July 6, 2016
Last Update Posted : April 30, 2021
Information provided by (Responsible Party):
Soonjo Hwang, MD, University of Nebraska

Brief Summary:

Irritability and emotional dysregulation are recognized as serious aspects of psychopathology seen in in pediatric psychiatric patients. While various behavioral as well as psychopharmacological interventions have shown some efficacy in improving irritability and emotional dysregulation, there are no data determining the neurobiological mechanism of effect at the neural level. Previous studies have demonstrated that heightened amygdala response to negative emotional stimuli is closely related to irritability and emotional dysregulation in children and adolescents. Also, there are studies showing administration of oxytocin can decrease the heightened amygdala response to negative emotional stimuli across various psychiatric diagnoses. This study is a double-blind randomized trial of oxytocin for irritability and emotional dysregulation in the pediatric population. Neuroimaging modalities of fMRI and MEG are employed to probe the neuro-circuitry changes occurring as a result of the oxytocin intervention, specifically including heightened amygdala response to negative emotional stimuli and dysfunctional fronto-amygdala connectivity. The investigators will also investigate the genetic sequence of the oxytocin receptor in the study participants and its relationship with symptom profile and neural activity changes. Children and adolescents (age 10-18) with a diagnosis of disruptive mood and/or behavior disorders (including Attention Deficit/Hyperactivity Disorder [ADHD], Oppositional Defiant Disorder [ODD], Conduct Disorder [CD], and Disruptive Mood Dysregulation Disorder [DMDD]), and clinically significant levels of irritability and emotional dysregulation as measured by the Affective Reactivity Index Scale (score>/= 4).

2 weeks randomized, double-blind treatment with intranasal oxytocin (24 IU daily, or 12 IU daily if the weight is < 40kg) with assessment of diagnosis, symptom profiles (the Affective Reactivity Index [ARI], Inventory of Callous-Unemotional Trait [ICU], Behavior Assessment System for Children, second version [BASC-2], and Clinical Global Impression [CGI]) and pre- and post-oxytocin treatment neuroimaging (fMRI and MEG). The genetic sample will be obtained via buccal mucosa sampling.

Participants may receive outpatient clinically indicated follow-up care in the UNMC department of psychiatry or other local community agency as appropriate.

Condition or disease Intervention/treatment Phase
Mood Disorder Disruptive Behavior Disorders Drug: Oxytocin Drug: Placebo Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Investigating the Impact of Oxytocin on Irritability/Emotional Dysregulation in Children and Adolescents With Disruptive Behavior and Mood Disorders, and the Possible Mediating Role of Amygdala Activity
Actual Study Start Date : January 27, 2017
Estimated Primary Completion Date : January 2022
Estimated Study Completion Date : January 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mood Disorders
Drug Information available for: Oxytocin

Arm Intervention/treatment
Experimental: Oxytocin
Subjects weighing >40kg will receive a total of 24 IU of oxytocin delivered as 2- 6 IU puffs to each nostril once daily. Subjects weighing < 40kg will receive a total of 12 IU of oxytocin delivered as 1- 6 IU puff to each nostril daily. Subjects will receive 14 to 21 days of daily oxytocin administration.
Drug: Oxytocin
A growing body of data shows that intra-nasal administration of oxytocin has promise for treating a host of psychiatric disorders. Considerable data indicates that oxytocin reduces amygdala response to negative stimuli in patients with generalized anxiety disorder, borderline personality disorder, and post-traumatic stress disorder. Given that one of the potential underlying neurobiological mechanisms of irritability and emotional dysregulation in pediatric population with disruptive behavior and mood disorder is the hyperactivity of amygdala to negative emotional stimuli, and that oxytocin reduces this, it is critical to determine the extent to which this intervention improves irritability and emotional dysregulation in children and adolescents with disruptive behavior and mood disorders.
Other Name: Pitocin

Placebo Comparator: Placebo
Subjects weighing>40kg will 2 puffs of placebo to each nostril daily. Subjects weighing <40kg will receive 1 puff per day. Subjects will receive 14-21 days of placebo administration.
Drug: Placebo
Inactive substance administered in volume equivalent to volume administered in active treatment arm.
Other Name: Saline

Primary Outcome Measures :
  1. Affective Reactivity Index Changes [ Time Frame: baseline and 14 days ]
    ARI is a 7 item inventory (self-report and parent-report versions) specifically designed to measure irritability and emotional dysregulation (Stringaris et al., 2012).

Secondary Outcome Measures :
  1. Behavior Assessment System for Children, second version (BASC-2) Changes [ Time Frame: baseline and 14 days ]
    BASC-2 is parent-reported, well-established scale for externalizing/internalizing problem of children and adolescents (Reynolds, 2004).

  2. Inventory of Callous Unemotional Trait (ICU) Changes [ Time Frame: baseline and 14 days ]
    ICU is a 24 item inventory specifically designed to measure callous-unemotional trait in children and adolescents (Berg et al., 2013; Frick, 2004).

  3. Reactive-Proactive Aggression Questionnaire (RPAQ) Changes [ Time Frame: baseline and 14 days ]
    RPAQ is a 23 item inventory (self-report) specifically designed to measure two different types of aggressive behavior, i.e., reactive and proactive aggression (Raine et al., 2006).

  4. functional MRI (fMRI) BOLD response changes [ Time Frame: baseline and 14 days ]
  5. Magneto-encephalography (MEG) electrical activity changes [ Time Frame: baseline and 14 days ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   10 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • 10-18 years of age
  • A current diagnosis of ADHD, ODD, CD, or DMDD as determined by the Kiddie-SADS, lifetime version
  • Clinically significant level of irritability as defined by a score of >/=4 on the Affective Reactivity Index (ARI) (Stringaris et al., 2012)
  • If currently on medication, medication treatment must be stable for at least 6 weeks with a stimulant medication, alpha 2 agonist, atomoxetine or antidepressant.

Exclusion Criteria:

  • Comorbid psychotic, tic, pervasive developmental, or substance abuse disorders
  • Major medical illness that prohibits treatment by oxytocin (e.g., severe liver disease, seizure disorder, metabolic disorder)
  • Past history of significant worsening of pre-existing psychiatric symptoms after treatment with oxytocin
  • Past history of allergic reaction to oxytocin and its nasal spray product
  • History of CNS disease (including history of seizure, epilepsy, CNS tumor, CNS hemorrhage, or serious CNS infection including meningitis or encephalitis)
  • Current use of antipsychotic medications and anxiolytics (benzodiazepines and barbiturates).
  • A positive urine pregnancy test
  • A positive urine drug screen or any history of or currently active diagnosis of substance use disorder
  • Wechsler Abbreviated Scale of Intelligence (WASI) (D. Wechsler, 1999) scores < 70
  • Metal in body (i.e., hearing aid, cardiac pacemaker, bone plates, braces, non-removable piercings/implants, etc), claustrophobia, or any other condition that would preclude fMRI scanning

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02824627

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Contact: Brigette S Vaughan, MSN, APRN 402-552-6239

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United States, Nebraska
University of Nebraska Medical Center Department of Psychiatry Recruiting
Omaha, Nebraska, United States, 61898-5581
Contact: Brigette S Vaughan, APRN    402-552-6239   
Principal Investigator: Soonjo Hwang, MD         
Sponsors and Collaborators
University of Nebraska
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Principal Investigator: Soonjo Hwang, MD Assistant Professor, University of Nebraska Medical Center
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Soonjo Hwang, MD, Assistant Professor, University of Nebraska Identifier: NCT02824627    
Other Study ID Numbers: 321-16-FB
First Posted: July 6, 2016    Key Record Dates
Last Update Posted: April 30, 2021
Last Verified: April 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Mood Disorders
Mental Disorders
Problem Behavior
Attention Deficit and Disruptive Behavior Disorders
Pathologic Processes
Behavioral Symptoms
Neurodevelopmental Disorders
Reproductive Control Agents
Physiological Effects of Drugs