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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 58
- 试验地点
- 1
- 主要终点
- Change in Affective Reactivity Index - Youth (ARI-Y)
研究概览
简要总结
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.
详细描述
- Clinical assessment
Standard clinical practice at the outpatient clinic of the department of psychiatry, at University of Nebraska Medical Center involves an initial clinical interview by either a child and adolescent psychiatrist faculty member, a child and adolescent psychiatry clinical fellow, or an advanced practice registered nurse. The clinical interview includes past and current history of psychiatric symptoms/signs, past and current medical history, and past/current social/academic history. Also the current medication (if any) and any medical condition that would have interaction with the psychiatric diagnosis will be reviewed. The child/adolescent will receive the diagnosis of psychiatric syndrome at the end of the assessment sessions. 2. Recruitment to the study
Participants diagnosed with ADHD/CD/ODD/DMDD and presence of clinically significant irritability and emotional dysregulation at the clinical assessment session will be invited to participate in this study afterwards. Participants who respond to advertisement, after a phone screening session will be also invited. 3. Initial research assessment
Participants who agreed to be enrolled into the protocol will have the initial research assessment session afterwards. This will be held at the outpatient clinic of the department of psychiatry, at University of Nebraska Medical Center. Participants will receive the Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS), to confirm the diagnosis of ADHD/CD/ODD/DMDD, and to rule out any other psychiatric diagnoses listed in the exclusion criteria. Their IQ will be measured by the Wechsler Abbreviated Scale of Intelligence (2-subtest form). Irritability and emotional dysregulation will be measured by the Affective Reactivity Index (ARI). Only the children and adolescents with diagnoses of ADHD/CD/ODD/DMDD and clinically significant level of irritability/emotional dysregulation (score >4 on the ARI) will be enrolled in the study. CBCL, ICU, RPAQ will be used to measure the symptom profiles and functional impairment of patients with ADHD/CD/ODD/DMDD at the initiation and end point of their study participation. 4. fMRI visit 1
During the MRI visit 1, participants will receive their first fMRI session immediately before initiation of oxytocin or placebo treatment. The fMRI visit 1 can happen on the same day of the initial research assessment after the initial research assessment is completed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 10 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Oxytocin (Drug)
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.
干预措施: Placebo (Drug)
结局指标
主要结局
Change in Affective Reactivity Index - Youth (ARI-Y)
时间窗: baseline and 21 days
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.
Clinical Global Impression: Severity
时间窗: 21 days (study endpoint)
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.
次要结局
- Functional MRI (fMRI) BOLD Response Changes(baseline and 21 days)