Phase 2
N=58
Oxytocin on Irritability/Emotional Dysregulation of Disruptive Behavior and Mood Disorders
Mood Disorder · Disruptive Behavior Disorders
Bottom Line
View on ClinicalTrials.gov: NCT02824627 ↗Enrolled (actual)
58
Serious AEs
0.0%
Results posted
Aug 2022
Primary outcome: Primary: Change in Affective Reactivity Index - Youth (ARI-Y) — -2.9; -0.8 score on a scale
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Oxytocin (Drug); Placebo (Drug)
- Age
- Pediatric, Adult · 10+ yrs
- Sex
- All
- Sponsor
- University of Nebraska
- Primary completion
- Aug 2021
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Change in Affective Reactivity Index - Youth (ARI-Y) |
-2.9; -0.8 | — |
| PRIMARY Clinical Global Impression: Severity |
2.72; 3.33 | — |
| SECONDARY Functional MRI (fMRI) BOLD Response Changes |
-0.045; 0.045 | — |
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.
Eligibility Criteria
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
Data sourced from ClinicalTrials.gov (NCT02824627). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.