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

Status

Completed

Phase

Phase 2

Enrollment

58 participants (actual)

Sponsor

University of Nebraska · Other

Design

Randomized · Quadruple masking

Countries

1 country

United States

Start

27 Jan 2017

Primary completion

10 Aug 2021

Completion

10 Aug 2021

First posted

6 Jul 2016 (estimated)

Last update posted

5 Oct 2023

Conditions

Mood Disorder · Disruptive Behavior Disorders

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.

• 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.

• 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.

1. Change in Affective Reactivity Index - Youth (ARI-Y)

   Time frame · baseline and 21 days

   Registry description

   The Affective Reactivity Index-Youth (ARI-Y) is a 7 item inventory (youth self-report) specifically designed to measure irritability and emotional dysregulation as a dimensional construct across psychopathologies in children and adolescents (Stringaris et al., 2012). ARI scores range from 0 to 12. Total scores are reported. Higher scores are indicative of more (worse) irritability. We report the change in ARI-Y score as our outcome measure.

2. Clinical Global Impression: Severity

   Time frame · 21 days (study endpoint)

   Registry description

   The Clinical Global Impression: Severity scale is a single-item clinician rated measure of the clinician's impression of the degree of illness of the subject in terms of level of irritability from study start to endpoint. Ratings are 1=normal, not ill, 2= borderline ill, 3= minimally ill, 4= moderately ill, 5= markedly ill, 6= severely ill; 7= very severely ill. A single score of 1 to 7 is given at study endpoint for each subject. A higher score indicates worsening of the subject's irritability based on clinician impression.

No study cites this trial.