Aggressive behavior in children and adolescents with Conduct Disorder (CD) or Oppositional Defiant Disorder (ODD) MedDRA version: 21.1 Level: LLT Classification code 10037183 Term: Psychic disturbance System Organ Class: 100000004873
Conditions
Interventions
Trade Name: Risperdal
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: RISPERIDONE
CAS Number: 106266-06-2
Current Sponsor code: Janssen-Cilag SpA
Other descriptive name: RISPERIDONE
Conce
Sponsors
RADBOUD UNIVERSITY MEDICAL CENTER
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: ODD/CD GROUP: - IQ = 80 (Wechsler IQ scale, within the last two years before enrolment); - Age between 10 years and 17 years and 10 month at the screening visit - Diagnosis of ODD or CD, based on the DSM-5 including the semi-structured K-SADS-PL interview; - Aggression in the clinical range, T = 70 on the aggression or delinquency subscale of the Teacher Report Form (TRF), Youth Self Report (YSR), or Child Behaviour Checklist (CBCL); or score = 27 on the Nisonger-CBRF D-Total (composite of Disruptive Behavior Disorder subscales); - The patient is eligible to be treated with a pharmacological therapy based on previous medical and instrumental cardiological assessments (personal and family cardiological history, ECG within the last six months; see 5.2.1.1) and based on previous blood chemistry (performed within the last six months), current physical and neurological examination; - Patient is drug-naive for psychotropic medications or off any psychotropic medication (Psychostimulants, antipsychotics, SNRI, mood stabilizers or antidepressant) within the last six months. - If the patient is a girl who is sexually active and of childbearing potential (WOCBP: Women of Childbearing Potential, defined as females aged =10 years old and younger girls who, at the discretion of the investigator, are deemed to be of reproductive potential), must have a negative urine pregnancy test at the Screening visit and at Baseline visit prior to randomization for phase III. The urine pregnancy test will be repeated, each week, during the randomised single-blind, placebo controlled, single dose, cross-over, acute challenge phase. The inclusion of WOCBP will require, throughout the study period, the use of condom and one of the following highly effective contraceptive measures: intrauterine devices, hormonal contraceptives (oral, depot, patch, injectable, or vaginal ring). ¿Other acceptable contraception methods are: ¿double barrier methods (e.g., condoms and diaphragms with spermicidal gel or foam). - Subjects’ parents/legal guardians must provide and sign informed consent documents; patients must provide informed consent, and sign consent or assent documents if capable and permitted according to the legal requirements in the country; - Patients meeting criteria for comorbid ADHD, Depression, Anxiety or PTSD (as to the clinical judgment of the investigator) will not be excluded from study participation. TYPICALLY DEVELOPING (TD) CONTROLS GROUP: - IQ = 80 (Wechsler IQ scale, within the last two years before enrolment); - Age between 10 years and 17 years and 10 month at the screening visit; - Aggression below the clinical range, T < 70 on the aggression or delinquency subscale of the Teacher Report Form (TRF), Youth Self Report (YSR), Child Behaviour Checklist (CBCL); and score < 27 on the Nisonger-CBRF D-Total (composite of Disruptive Behavior Disorder subscales); - Subjects have to be drug-naive for psychotropic medications; - Subjects’ parents/legal guardians must provide and sign informed consent documents; TD control must provide informed consent, and sign consent or assent documents if capable and permitted according to the legal requirements in each country; - Subjects meeting criteria for any psychiatric condition will be excluded from study participation. - If the patient is a girl who is sexually active and WOCBP, must have a negative urine pregnancy test at the Screening visit and at Baseline visit. Are the trial subjects under 18? yes Number of
Exclusion criteria
Exclusion criteria: ODD/CD GROUP: - IQ < 80 (Wechsler IQ scale, within the last two years before enrolment); - The subject has a primary DSM-5 diagnosis of schizophrenia-related disorders, schizophrenia, bipolar disorder, Autistic Spectrum Disorder, depression or anxiety; - The subject had any psychotropic medications (Psychostimulant, antipsychotics, SNRI, antidepressant, mood stabilizers) within the last six months before screening visit; - The subject is pregnant or nursing; - The subject has a body weight < 30 Kg - The subject has any acute or unstable medical condition that, in the opinion of the investigator, would compromise participation in the study. The patient will be excluded if presents with one or more of the following conditions: neurological disorder, other psychiatric disorder, cardiovascular disease, seizure disorder on encephalopathy, congestive heart failure, cardiac hypertrophy, arrhythmia, bradycardia (pulse<50bpm), respiratory disease, hepatic impairment or renal insufficiency, metabolic disorder, endocrinological disorder, gastrointestinal disorder, haematological disorder, infectious disorder, any clinically significant immunological condition, dermatological disorder, congenital or juvenile glaucoma or is at risk of acute narrow-angle glaucoma - The subject has a history of severe allergies to medications, in particular hypersensitivity to neuroleptics, or of multiple adverse drug reactions, or the patient has any contraindications to the use of the study drugs as following: Metilphenidate and Atomoxetine are contraindicated in patients known to be hypersensitive to these drugs or other components of the products; in patients with glaucoma; during treatment with monoamine oxidase inhibitors, and also within a minimum of 14 days following discontinuation of a monoamine oxidase inhibition; in patients with severe hypertension, angina pectoris, cardiac arrhythmias, heart failure, recent myocardial infarction, hyperthyroidism or thyrotoxicosis. Risperidone is contraindicated in patients with a known hypersensitivity to either risperidone or paliperidone, or to any of the excipients in the formulation. Aripiprazole is contraindicated in patients with a history of a hypersensitivity reaction to aripiprazole. Moreover Aripiprazole and Risperidone must be used with caution in subjects with a history of seizures, hypertension, angina pectoris, cardiac arrhythmias, heart failure, recent myocardial infarction, cerebrovascular adverse event, dyslipidemia and metabolic changes, a history of leukopenia, neutropenia, and agranulocytosis, or of hepatic impairment or renal insufficiency, neuroleptic malignant syndrome (NMS), diabetes, in patients with previous hyperprolactinemia, orthostatic hypotension suicidal thoughts and behaviors, alcohol abuse or dependence. TYPICALLY DEVELOPING (TD) CONTROLS GROUP: - IQ < 80 (Wechsler IQ scale, within the last two years before enrolment); - the subject has a primary DSM-5 diagnosis of ADHD, ODD, CD or any other psychiatric condition; - The subject had any psychotropic medications (Psychostimulant, antipsychotics, SNRI, antidepressant, mood stabilizers) within the last six months before screening visit. - The subject is pregnant or nursing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Our main goal is to first compare neuropsychological and autonomic functioning in children and adolescents with clinically relevant levels of aggression and diagnosis of ODD or CD to Typically Developing (TD) controls. We primarily aim to explore if conduct problems and aggression symptoms are related to specific neuropsychological (attention, working memory, decision making and risk taking, social cognition, delay aversion, emotional processing, motivation, cooperation, reward-punishment sensitivity), and autonomic (hearth rate, skin conductance, salivary cortisol) profiles, in order to differentiate subjects with aggression and CD/ODD from healthy controls. Moreover our aim is to examine if specific neuropsychological and autonomic profiles in patients with aggression symptoms permit to distinguish between reactive (“impulsive”, “affective” or “overt”) versus instrumental (“predatory”, “planned”) aggression in order to better subtyping different aggressive behaviours. ;Secondary Objective: 1) we will investigate the acute effects of medications, known to impact positively on aggression in the context of CD/ODD. In particular we aim to identify the acute effect of medication on specific neuropsychological and physiological features possibly underlying different types of aggression (reactive/instrumental aggression). For this purpose, we will specifically explore the responses to an acute medication challenge by the administration of a single dose of a stimulant, a not stimulant SNRI and two antipsychotic medications (Methylphenidate, Atomoxetine, Risperidone, Aripiprazole). 2) We will evaluate the moderating or modulating role on the neuropsychological/autonomic response of the following variables: presence of Callous-unemotional traits, comorbidities, SES, age and gender, previous medication, source of information (patient, parents, teacher, clinician evaluation), family structure.;Primary end point(s): 1) Reaction times, accuracy, test completio | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The following measures will be used to investigate the association between severity, type of aggression and performance on the neuropsychological tasks: • screening questionnaires: Teacher Report Form (TRF), Youth Self Report (YSR), Child Behavior Checklist (CBCL), The Conners’ Parent Rating Scale-Revised (CPRS-RS), Behavior Rating Inventory of Executive Function (BRIEF), Inventory of Callous-Unemotional Traits (ICU) • screening rating scales: Modified Overt Aggression Scale (MOAS) and Nisonger Child Behavior Rating Form Typical IQ version (NCBRF-TIQ) interview • Clinical Global Impression-Severity (CGI-S), Children’s Global Assessment (C-GAS) ;Timepoint(s) of evaluation of this end point: Secondary endpoints will be assessed during the screening visit. | — |
Countries
Italy
Contacts
Public ContactProject Management
Università di Cagliari - Dipartimento di Scienze Biomediche, Clinica di Neuropsichiatria Infantile
Outcome results
None listed