Plain English Summary
Background and study aims
Risperidone is a drug that is widely prescribed to children and adolescents with a variety of conditions that cause aggressive behaviour, such as Conduct Disorder (CD). The effectiveness and safety of risperidone have been shown in children and adolescents with mild mental retardation but there is a lack of data regarding patients with an average IQ. The long-term safety of risperidone is also a matter of concern since children and adolescents seem particularly vulnerable to side effects such as weight gain. The aim of this study is to examine the effectiveness and safety of risperidone in children and adolescents with CD and normal IQ.
Who can participate?
Patients aged 5 to 18 with CD and an IQ of at least 85.
What does the study involve?
Patients are randomly allocated to be treated with either risperidone or placebo (dummy medication) for 12 weeks.
What are the possible benefits and risks of participating?
Aside from the possible side effects of risperidone no other risks are involved.
Where is the study run from?
This study takes place at hospitals and psychiatrist centers in the Netherlands, UK, Germany, Belgium, France, Spain and Italy.
When is the study starting and how long is it expected to run for?
April 2012 to April 2015.
Who is funding the study?
European Community's Seventh Framework Programme
Who is the main contact?
Prof. Dr JK Buitelaar
j.buitelaar@psy.umcn.nl
Trial website
Contact information
Type
Scientific
Primary contact
Prof Jan K Buitelaar
ORCID ID
Contact details
Radboud University Nijmegen Medical Centre
Reinier Postlaan 12
Nijmegen
6525 CG
Netherlands
-
j.buitelaar@psy.umcn.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
PERS2 - NTR3218
Study information
Scientific title
A randomized double blind, placebo controlled study of risperidone in the treatment of DSM-IV-TR conduct disorder in children and adolescents
Acronym
Study hypothesis
Risperidone given orally in a dose of 0.25 mg/d 3.0 mg/d depending on body weight (equivalent to approximately 0.01 0.04 mg/kg/d) for 12 weeks is superior to placebo in reducing disruptive behavioural symptoms associated with Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) defined Conduct Disorder (CD) in the treatment of inpatient and outpatient children and adolescents (aged 5 years to 17 years and 9 Months), who are not developmentally delayed/mentally retarded.
Ethics approval
CMO Region, Arnhem-Nijmegen, The Netherlands, 09/02/2012
Study design
Multicenter randomized double-blind parallel placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Patient information material can be found at http://www.pers-project.com/index.php/why-should-i-or-my-kid-participate-in-the-pers-studies/
Condition
Conduct disorder / Oppositional Defiant Disorder
Intervention
Study Period I will be a 2 week screening (and washout) period
Study Period II will be a 12-week double-blind, randomized, placebo-controlled period
Study Period III will be a double-blind 1 week down-titration period.
This study involves a comparison of risperidone in the range of 0.25 mg/d 3.0 mg/d (equivalent to approximately up to 0.04 mg/kg/d) with placebo.
During Study Period II, dosing of risperidone will be initiated and modified according to the weight group of the patient at Baseline (Visit 3). Dosing may then be increased (or decreased) by 0.25 mg/d (or 0.5mg/kg/d increments, respectively, at specified visits/dates according to the weight of the subject, with minimum daily doses of 0.25 mg/day for patients under 50 kg body weight and 0.5 mg/day for patients who weigh 50 kg or more. Stepwise up-titration is recommended to the target dose or the highest tolerable dose by week 8. Dosing should remain stable during the last 4 weeks of Study Period II, unless a dose reduction is necessary for safety or tolerability reasons. In case of dose-adjustments due to adverse events unscheduled visits can be performed (for stepwise down-titration).
There are three study periods. Study Period I is a 2 week screening and washout period; during this period patients will be screened for study eligibility. Study Period II is a 12-week, randomized, double-blind, and placebo-controlled acute treatment period. Patients will be randomly assigned to risperidone or placebo in a 1:1 ratio. For patients in the risperidone treatment group, dosing will begin in either 0.25 or 0.5 mg/d, given in the evening depending on the patient‟s weight, and will be up-titrated by 0.25 mg/d or 0.5 mg/d increments each week to maximum doses that vary by patient weight. Study Period III is a 1 week double-blind down-titration period from study medication, risperidone, or placebo. Any patient who completes Study Period II will continue into Study Period III. In order to keep the blind, all patients will receive the respective amounts of study drug (risperidone or placebo).
Intervention type
Drug
Phase
Not Applicable
Drug names
Risperidone
Primary outcome measure
1. Nisonger Child Behavior Rating Form (CBRF)
2. Typical IQ Version-ODD/CD disruptive behavior (DBD)
3. Composite Total score (Aman et al., 2008) using investigator-ratings based on all available information
Secondary outcome measures
The secondary outcome measures focus on assessment of changes with active treatment vs. placebo:
1. Clinical Global Impressions-Improvement (CGI-I) and Clinical Global Impressions-Severity (CGI-S) (Guy 1976; NIMH 1985)
2. Children's Global Assessment Scale (C-GAS) (Shaffer et al., 1983)
3. ADHD-DSM IV_RS (DuPaul et al., 1998)
4. OAS (Yudofsky et al., 1986)
5. Child Health & Illness Profile - Child Edition (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 Suicide Severity Rating (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.
Overall trial start date
01/04/2012
Overall trial end date
01/04/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. This study will include male and female inpatients or outpatients
2. Aged between 5 years and 17 years and 9 months
3. Patients must meet DSM-IV-TR diagnostic criteria for DSM-IV-TR Conduct Disorder(s)
4. Patients must have an IQ of > 85
5. 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
6. Patients must have a body weight of at least 20 kg at study entry
7. Patients must be able to swallow study drug
8. Patients must have venous access sufficient to allow blood sampling and are compliant with blood draws
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
264
Participant exclusion criteria
1. 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
2. Has participated in any investigational drug trial within six months prior to baseline
3. 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
4. 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).
5. In the clinical judgment of the investigator, currently meets criteria for a primary psychiatric disorder, e.g., Anxiety Disorder, Depressive Disorder, Tic Disorder or Tourettes Syndrome
6. Starts any psychotropic medication, including health-food supplements that the investigator feels could have central nervous system activity
7. 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.
8. Has a known or suspected seizure disorder
9. Has a history of neuroleptic malignant syndrome (NMS) or of tardive dyskinesia
10. Has a history of hypersensitivity to neuroleptics
11. Is pregnant or nursing
Recruitment start date
01/04/2012
Recruitment end date
01/04/2015
Locations
Countries of recruitment
Belgium, France, Germany, Italy, Netherlands, Spain, United Kingdom
Trial participating centre
Radboud University Nijmegen Medical Centre
Nijmegen
6525 CG
Netherlands
Sponsor information
Organisation
Radboud University Nijmegen Medical Centre (Netherlands)
Sponsor details
c/o Prof. Jan K. Buitelaar
Reinier Postlaan 12
Nijmegen
6525 CG
Netherlands
Sponsor type
Hospital/treatment centre
Website
Funders
Funder type
Government
Funder name
Seventh Framework Programme
Alternative name(s)
EC Seventh Framework Programme, European Commission Seventh Framework Programme, EU Seventh Framework Programme, European Union Seventh Framework Programme, FP7
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list