Conduct Disorder Children Adolescents Aggression Risperidone Efficacy Safety Tolerability Agressie Kinderen Adolescenten Risperidon Medicatie Effectiviteit Veiligheid
Conditions
Interventions
Participants will receive either the risperidone or the placebo tablets for the duration of 12 weeks.
Drug 1: These tablets contain 0.25 mg, 0.5 mg or 1.0 mg of Risperidone. The maximum daily dose in
Drug 2: These tablets contain a so-called placebo. Placebos look like drug 1, but don¡¯t contain any medically active components.
Sponsors
Prof J.K. Buitelaar, Radboud University Medical Centre, Nijmegen, The Netherlands
Eligibility
Inclusion criteria
Inclusion criteria: Patients are eligible to be included in the study only if they meet all of the inclusion criteria below: 1. Male or female patients aged 5.0 - 85 (based on, e.g., 4 WISC subtests): vocabulary, similarities, block design, and matrix reasoning (cf. Crawford et al., 2010. Age- and country-specific adaptations will be used; 3. Patients must meet DSM-IV-TR diagnostic criteria for DSM-IV-TR Conduct Disorder(s) as confirmed by the Kiddie-SADS, Conduct Disorder Module: 312.8x. (Kaufman et al., 1996), at Visit 2 or Visit 3; 4. Patients must score ¡Ã 27 on the Nisonger CBR Form, ODD/CD Disruptive Behavior Composite (D-Total) either at Visit 2 or Visit 3; 5. Patients must score ¡Ã4 (¡°moderately ill¡± (or > 5, ¡°markedly ill¡±) on the CGI-S rating scale at Visits 2 and 3; 6. If a female of child-bearing potential, patients must test negative for pregnancy at the time of enrollment based on a serum pregnancy test and agree to use a reliable method of birth control. (Adequate contra- ception includes: oral contraceptives, intraueterine devices; double barrier method (diaphragm or condom plus spermicide), Norplant¢â or Depot Provera¢â)); 7. Patients must have a body weight of at least 20 kg at study entry; 8. Patients must be able to swallow study drug; 9. Patients must have venous access sufficient to allow blood sampling and are compliant with blood draws as per protocol; 10. Subjects¡¯ parents/legal guardians must provide and sign informed consent documents; Patients must provide informed consent, and sign consent or assent documents if capable, according to the legal requirements in the very country; 11. A reliable person (primary caregiver, parent) must be available to ensure compliance with study procedures throughout the course of the study; 12. Patients meeting criteria for comorbid ADHD (as to the clinical judgment of the investigator) will not be excluded from study participation.
Exclusion criteria
Exclusion criteria: A patient will be excluded from the study if he or she meets any exclusion criteria described below, according to the assessment of the investigator: 1. Is immediate family of investigator site personnel directly affiliated with this study. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted; 2. Has been treated with a drug within 14 days before Visit 1 that has not received regulatory approval for any indication at the time of study entry; 3. Has participated in any investigational drug trial within six months prior to baseline (visit 3); 4. Has previously completed or withdrawn from this study or any other study investigating risperidone or has previously been identified as being a nonresponder or intolerant of risperidone; 5. Has a current (within 6 months of the start of the study) or lifetime DSM-IV-TR diagnosis of schizophrenia-related disorders, schizophrenia, bipolar disorder, major depressive disorder, or current substance dependence disorder (given the nature of the study population substance misuse or abuse is not exlusionary), pervasive developmental disorder (autistic disorder or Asperger disorder); 6. In the clinical judgment of the investigator, meets criteria for a primary psychiatric disorder, e.g., Anxiety Disorder, Depressive Disorder, Tic Disorder or Tourette¡¯s Syndrome (comorbid ADHD is permitted, cf. Incl. criteria section); 7. Starts any psychotropic medication, including health-food supplements that the investigator feels could have central nervous system activity (for example, St. John¡¯s Wort, melatonin), during the course of the study, or is taking any other excluded concomitant medication(s) at/beyond Visit 2 (specified in Section 5.7). (An ongoing long-term medication, e.g., to treat a comorbid disorder such as ADHD, is permitted as long as compound and dose are not changed throughout the course of the study.); 8. Has any acute or unstable medical condition, physiological condition, clinically significant laboratory, or ECG results that, in the opinion of the investigator, would compromise participation in the study; 9. Has a known or suspected seizure disorder; 10. Has a history of neuroleptic malignant syndrome (NMS) or of tardive dyskinesia; 11. Has a history of hypersensitivity to neuroleptics, of tardive dyskinesia, or neuroleptic malignant syndrome; 12. Is pregnant or nursing.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The rating scales used in this study are accepted methods for assessing the respective variables for which they were developed. It is proposed that treatment with risperidone may reduce disruptive behaviour so that patients suffering from CD can function better and engage more effectively in their external environment. The use of the ODD/CD (D-Total) composite of the Nisonger CBRF-TIQ ( Aman et al., 2008) as the primary outcome measure will assess the effect of risperidone treatment on disruptive behaviour. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary outcome measures focus on assessment of changes with active treatment vs. placebo: 1. CGI-I and CGI-S (Guy 1976; NIMH 1985); 2. C-GAS (Shaffer et al., 1983); 3. ADHD-DSM IV_RS (DuPaul et al., 1998); 4. OAS (Yudofsky et al., 1986); 5. CHIP-CE (Riley et al., 2004); 6. Child Behavior Checklist (CBCL), parent-reported (Achenbach, 1991a); 7. PAERS (March et al., 2007) (The PAERS will be used to evaluate AEs in a standardized approach (March et al., 2007); 8. ANT subtests (de Sonneville, 1999); 9. Columbia SSR (Posner et al., 2007b); 10. Additional outcomes related to Informed Consent procedures, Treatment Compliance, etc., potential mediators and moderators for efficacy and tolerability/safety parameters. Previous placebo-controlled studies in children and adolescents with CD with risperidone have shown that patients treated with risperidone manifested increases in body weight compared with placebo (Reyes et al. 2006a, Shea et al. 2004). Therefore it is appropriate to monitor patients¡¯ weight and BMI throughout the study. In addition, it is also appropriate for patients taking second-generation antipsychotics such as risperidone to have, e.g., their fasting lipid profile, fasting glucose, blood pressure, and prolactin monitored. | — |
Contacts
Public ContactJeffrey Glennon
Dept. of Cognitive Neuroscience Radboud University Nijmegen Medical Centre
Outcome results
None listed