Oxytocin on Irritability/Emotional Dysregulation of Disruptive Behavior and Mood Disorders
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|ClinicalTrials.gov Identifier: NCT02824627|
Recruitment Status : Recruiting
First Posted : July 6, 2016
Last Update Posted : March 5, 2019
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|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||60 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|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 2017|
|Estimated Primary Completion Date :||January 2020|
|Estimated Study Completion Date :||January 2020|
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.
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.
Inactive substance administered in volume equivalent to volume administered in active treatment arm.
Other Name: Saline
- 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).
- 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).
- 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).
- 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).
- functional MRI (fMRI) BOLD response changes [ Time Frame: baseline and 14 days ]
- Magneto-encephalography (MEG) electrical activity changes [ Time Frame: baseline and 14 days ]
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 ClinicalTrials.gov identifier (NCT number): NCT02824627
|Contact: Brigette S Vaughan, MSN, APRNfirstname.lastname@example.org|
|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 email@example.com|
|Principal Investigator: Soonjo Hwang, MD|
|Principal Investigator:||Soonjo Hwang, MD||Assistant Professor, University of Nebraska Medical Center|