The primary objective is to test the hypothesis that, after at least 15 weeks of daily administration (4 for titration, 7 of relatively stable dose, 4 at fixed doses; Study Period II), risperidone given orally in a dose of 0.25 - 3.0 mg/d depending…
ID
Source
Brief title
Condition
- Psychiatric and behavioural symptoms NEC
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Clinical response is defined as > 25 % reduction from baseline score on the
Nisonger CBRF-TIQ D-Total subscale at endpoint (based on a personal
communication of the scale author, Dr. Michael Aman, June 2010) and a score of
1 or 2 (*much* or very much* improved) on the CGI-Improvement scale.
Secondary outcome
Relapse rate, with relapse defined a CGI-S rating > 2 points, compared to the
prediscontinuation baseline, and a 25% increase in the score on the pivotal
Nisonger CBRF-TIQ D-Total scale for at least two consecutive visits, 12-16 days
apart (Reyes et al., 2006).
Background summary
Conduct disorder (DSM-IV-TR; 312.8x* APA, 2000) (CD) is defined as *a
repetitive and persistent pattern of behavior* in which the basic rights of
others or major age-appropriate societal norms or rules are violated, as
manifested by the presence of three (or more) of 15 criteria in the past 12
months, related to categories: aggression to people and animals, destruction of
property, deceitfulness or theft, and serious violations of rules.
Risperidone, a second generation antipsychotic, is increasingly used for the
treatment of aggression and disruptive behaviors in the context of conduct
disorder as defined by DSM-IV. Among the second generation antipsychotics
risperidone is the most extensively studied medication for the treatment of
aggression and CD in children and adolescents.
A meta-analysis of 9 RCTs of the effect of risperidone in reducing symptoms of
aggression included 875 subjects (81.1% male; mean age = 9.2 years) and
reported a large effect size of 0.9 (Pappadopulos et al., 2006). The majority
of these studies, however, have been conducted in children and adolescent with
mental retardation.
Currently, there are insufficient data available about short-term efficacy and
safety/tolerability of using medication, e.g. risperidone, in children and
adolescents with conduct disorder with about average IQ (85 and above). For
these patients there are virtually no data available about the maintenance of
their therapeutical effect over time and insufficient data are available about
the long-term safety (treatment for at least 2 years) of using risperidone in
children and adolescents with conduct disorder (or other indications).
Study objective
The primary objective is to test the hypothesis that, after at least 15 weeks
of daily administration (4 for titration, 7 of relatively stable dose, 4 at
fixed doses; Study Period II), risperidone given orally in a dose of 0.25 - 3.0
mg/d depending on body weight (eq. to approximately 0.01 - 0.04 mg/kg/d) is
superior to placebo in preventing relapse of symptoms of CD, as assessed
through a 11 week, double-blind discontinuation trial (Study Period III) of
children and adolescents not developmentally delayed/mentally retarded, and
measured by comparison with mean change from the double-blind baseline to
endpoint on the Nisonger Child Behavior Rating Form (CBRF) - Typical IQ Version
(Aman et al., 2008) using investigator-ratings based on all available
information.
To establish the long-term efficacy of treatment with risperidone, measuring
mean change from the double-blind baseline to endpoint on the pivotal
(Nisonger) scale between risperidone and placebo,
To test the effect of risperidone compared to placebo on various behavioural
domains following seven months of daily administration of risperidone assessed
in a 11 week, double blind discontinuation trial
To compare changes (impairment) in neurocognitive function following
risperidone, assessed in both the 15 weeks open label and the 11-week
double-blind discontinuation trial
To assess the effect of risperidone compared to placebo on comorbid ADHD
symptoms following seven months of daily administration of risperidone assessed
in a 11-week, double-blind discontinuation trial
To compare safety and tolerability results for risperidone and placebo in
children and adolescents with CD over 11 weeks of double-blind treatment
Study design
This study is a multicentre, randomized, double-blind, parallel,
placebo-controlled 18-visit trial with four study periods in pediatric
patients, aged 5 to 17 years and five months, who meet the Diagnostic and
Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV*) criteria for
Conduct Disorder (CD).
In order to include 150 patients to the discontinuation phase of the study, 200
children and adolescents (50% children 5.0-12.0 years of age, 50% adolescents
12.0-17.5 yr) meeting DSM-IV-TR diagnostic criteria for DSM-IV CD disorders as
confirmed by the Kiddie-SADS, Conduct Disorder Module: 312.xx. (Kaufman et al.,
1996) will be enrolled.
They will undergo four study periods:
• Study Period I will be a screening period (2 visits)
• Study Period II will be a 15-week titration and open label treatment period
(7 visits).
• Study Period III will be a 11 week double-blind, randomized,
placebo-controlled discontinuation period (7 visits).
• Study Period IV will be a 2-week down titration period (2 visits)
All patients who complete Study Period II maintaining clinical response are
eligible to participate in Study Period III.
Intervention
This study involves the use of Risperidone at a dosage of 0.01-0.04 mg/kg per
day.
Study burden and risks
The burden and risk for particpation of this study have been kept to a minimum.
Most questionnaires are completed by the legal representatives
(parents/caregivers), to avoid the participation being to burnered with this.
Previous studies indicated that risperidone treated patients (without mental
retardation) showed improvement on interpersonal behaviour and rule compliance
and reductions in clinician-rated symptoms and agressive behaviour.
All efforts (Blood samples and psychical examination, including taking a
medical history, physical examinations, clinical lab test and urine test) are
according to international consensus and best clinical practise.
The experimental conditions are similar to clinical conditions. In the extent
of burden for participants of the study is not significantly other than in
clinical pratise except a few more questionnaires.
Geert Grooteplein 21
6525 EZ Nijmegen
NL
Geert Grooteplein 21
6525 EZ Nijmegen
NL
Listed location countries
Age
Inclusion criteria
Patients are eligible to be included in the study only if they meet all of the inclusion criteria below. ;[1] Patients (male or female) must be at least 5 years of age, and not more than 17 years and 5 months of age at Visit 1.
[2] Patients must meet DSM-IV-TR diagnostic criteria for DSM-IV CD (312.xx) as confirmed by the Kiddie-SADS, Conduct Disorder Module
[3] Patients must have an IQ of > 85
[4] Patients must score >= 27 on the Nisonger CBR Form, ODD/CD Disruptive Behavior Composite (D-Total) at baseline
[5] Patients must score >= 4 (*moderately ill* or *markedly ill*) on the CGI-S rating scale at both baseline measures
[6] Patients must have a body weight comprised between 5th and 95th percentile based on WHO Body Mass Index for age-sex specific charts, at study entry.
[7] Patients must be able to swallow the study drug.
[8] Patients must have venous access sufficient to allow blood sampling and are compliant with blood draws as per protocol.
[9] If the patient is a female with child-bearing potential, she must test negative for pregnancy (based on a urine pregnancy test) at the time of enrollment and agree to use a reliable method of birth control.
[10] Laboratory results, including serum chemistries, hematology and urinalysis, show no significant abnormalities (significant would include laboratory deviations requiring acute medical intervention or further medical evaluation) and there is no clinical information that, in the judgment of a physician, should preclude a patient*s participation at study entry.
[11] All patients must have an ECG at Visit 1 or 2. Results must be available prior to dispensing drug at Visit 3. If an ECG shows any severe abnormality, the patient must be excluded from the study. Patients with other abnormalities may be included at the discretion of the investigator.
[12] Patients meeting criteria for comorbid ADHD (as to the clinical judgement of the investigator) will not be excluded from study participation.
Exclusion criteria
A patient will be excluded from the study if he or she meets any exclusion criterion described below.;- Has previously completed or withdrawn from this study or has been previously identified as being a non-responder or intolerant of risperidone.
- Has been treated within 14 days before Visit 1 with a drug that has not received regulatory approval for any indication at the time of study entry, or has participated in any investigational drug trial within six months prior to baseline (visit 1).
- Has a current (within 6 months of the start of the study) or lifetime DSM-IV diagnosis of schizophrenia-related disorders, schizophrenia, bipolar disorder, major depressive disorder, pervasive developmental disorder (autistic disorder or Asperger disorder).
- In the clinical judgment of the investigator, currently meets criteria for a primary psychiatric disorder, e.g., Anxiety Disorder, Depressive Disorder, Tic Disorder or Tourette*s Syndrome (comorbid ADHD is permitted).
- 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) specified in protocol. (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).
- Has a history of hypersensitivity to neuroleptics, of tardive dyskinesia, or neuroleptic malignant syndrome.
- 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.
- Has a known or suspected seizure disorder.
- Female patients who are pregnant or breastfeeding.
- Patients with a history of severe allergies to more than 1 class of medications or multiple adverse drug reactions.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2010-021884-34-NL |
| CCMO | NL36396.091.12 |