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

NCT02824627 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 0321-16-FB
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

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.

Conditions

Mood Disorder; Disruptive Behavior Disorders

Outcome Measures

Primary Outcomes (2)

• Change in Affective Reactivity Index - Youth (ARI-Y)

  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.

  baseline and 21 days

• Clinical Global Impression: Severity

  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.

  21 days (study endpoint)

Secondary Outcomes (1)

• Functional MRI (fMRI) BOLD Response Changes

  baseline and 21 days

Study Arms (2)

Oxytocin

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

Oxytocin DRUG

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.

Also known as: Pitocin

Oxytocin

Placebo DRUG

Inactive substance administered in volume equivalent to volume administered in active treatment arm.

Also known as: Saline

Placebo

Eligibility Criteria

• Age: 10 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center, Department of Psychiatry

Omaha, Nebraska, 61898-5581, United States

Location

Related Publications (1)

• Seok JW, Bajaj S, Soltis-Vaughan B, Lerdahl A, Garvey W, Bohn A, Edwards R, Kratochvil CJ, Blair J, Hwang S. Structural atrophy of the right superior frontal gyrus in adolescents with severe irritability. Hum Brain Mapp. 2021 Oct 1;42(14):4611-4622. doi: 10.1002/hbm.25571. Epub 2021 Jul 20.

  PMID: 34288223 DERIVED

MeSH Terms

Conditions

Mood Disorders; Attention Deficit and Disruptive Behavior Disorders

Interventions

Oxytocin; Sodium Chloride

Condition Hierarchy (Ancestors)

Mental Disorders; Neurodevelopmental Disorders

Intervention Hierarchy (Ancestors)

Pituitary Hormones, Posterior; Pituitary Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Results Point of Contact

• Title: Soonjo Hwang
• Organization: University of Nebraska Medical Center

soonjo.hwang@unmc.edu

402-552-6351

Study Officials

• Soonjo Hwang, MD

  Assistant Professor, University of Nebraska Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 27, 2016
• First Posted: July 6, 2016
• Study Start: January 27, 2017
• Primary Completion: August 10, 2021
• Study Completion: August 10, 2021
• Last Updated: October 5, 2023
• Results First Posted: August 30, 2022

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)