A Study of the Effectiveness and Safety of Risperidone Versus Placebo in the Treatment of Children With Autistic Disorder and Other Pervasive Developmental Disorders (PDD)

Study Description

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Brief Summary:

The purpose of the study is to evaluate the effectiveness of an oral solution of risperidone (an antipsychotic medication) versus placebo in the treatment of behavioral symptoms in children with Pervasive Developmental Disorders (PDD).

Condition or disease	Intervention/treatment	Phase
DCild Development Disorders, Pervasive; Autistic Disorder; Developmental Disabilities; Asperger Syndrome; Rett Syndrome	Drug: risperidone	Phase 3

Detailed Description:

The Pervasive Developmental Disorders (PDD) are a group of neuropsychiatric disorders, including autistic disorder, characterized by specific delays and deviance in social, communicative, and cognitive development with an onset typically in the first years in life. Children with PDD may show multiple, serious symptoms including hyperactivity, inattention, impulsive and aggressive behavior, repetitive movements or speech patterns, sleep disorders, screaming, and self-injurious behavior. Drug studies to date have suggested that different behavioral symptoms of PDDs respond to neuroleptics, such as risperidone. This is a randomized, double-blind, placebo-controlled study to evaluate the effectiveness of risperidone (0.02 to 0.06 mg/kg/day) compared with placebo in the treatment of behavioral symptoms in children 5 to 12 years of age with Pervasive Developmental Disorders (PDD). Patients receive study medication (risperidone or placebo) to be taken orally once a day at gradually increasing doses up to a maximum of 0.06 mg/kg, adjusted at weekly intervals to achieve optimal effectiveness while minimizing any intolerance to the drug. Treatment continues at the optimal dose through Week 8. A parent or caregiver evaluates the child's behavior and symptoms at scheduled office visits during the course of treatment. The primary measure of effectiveness is the change in the Irritability Subscale of the Aberrant Behavior Checklist (ABC) and other ABC subscales at end of treatment compared with baseline. Additional assessments of effectiveness include: the Nisonger Child Behavior Rating Form (N-CBRF); the Visual Analogue Scale (VAS), a measure of the patient's most disturbing symptom; and the Clinical Global Impression (CGI) of the overall severity of the disorder. Safety assessments include the incidence of adverse events throughout the study; measurement of vital signs (pulse, temperature, blood pressure), body weight, and evaluation of the presence and severity of extrapyramidal symptoms by the Extrapyramidal Symptom Rating Scale (ESRS) at specified intervals; clinical laboratory tests (hematology, biochemistry, urinalysis) before study initiation and at the end of treatment. The study hypothesis is that risperidone is more effective than placebo for the treatment of behavioral symptoms in children aged 5 to 12 years with Pervasive Developmental Disorders (PDD). Risperidone oral solution 1 mg/mL or placebo, taken orally, once daily. Days 1 - 2, dose is 0.01 mg/kg body weight. Days 3 - 7 dose is 0.02 mg/kg, increasing on Days 8 - 14 to 0.04 mg/kg (maximum), and 0.06 mg/kg (maximum) through 8 weeks. Dosage may be adjusted at investigator's discretion.

Study Design

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	80 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double
Primary Purpose:	Treatment
Official Title:	Efficacy And Safety Of Risperidone In The Treatment Of Children With Autistic Disorder And Other Pervasive Developmental Disorders: A Canadian, Multicenter, Double-Blind, Placebo-Controlled Study
Study Start Date :	August 1999
Actual Study Completion Date :	December 2001

Arms and Interventions

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Outcome Measures

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. Change in the Irritability Subscale of the Aberrant Behavior Checklist (ABC) and other ABC subscales at end of treatment compared with baseline

Secondary Outcome Measures :

1. Change from baseline to end of treatment in Nisonger Child Behavior Rating Form (N-CBRF), Visual Analogue Scale (VAS), and Clinical Global Impression (CGI); incidence of adverse events throughout study.

Eligibility Criteria

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	5 Years to 12 Years (Child)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Diagnosis of Pervasive Developmental Disorders (Autistic Disorder, Rett's Disorder, Childhood Disintegrative Disorder, Asperger's Disorder, or Pervasive Development Disorder not Otherwise Specified) by Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), Axis I criteria
• with a total score of >=30 on the Childhood Autism Rating Scale (CARS)
• receiving treatment as an out-patient
• healthy on the basis of a physical examination, electrocardiogram (ECG), and medical history at start of the study.

Exclusion Criteria:

• Diagnosis of schizophrenia or other psychotic disorders by DSM-IV criteria
• seizure during 3 months prior to study initiation or currently being treated with more than one anticonvulsant drug
• history of tardive dyskinesia (a complication of neuroleptic therapy involving involuntary movements of facial muscles)
• neuroleptic malignant syndrome (a rare psychotropic-drug reaction, which may be characterized by confusion, reduced consciousness, high fever or pronounced muscle stiffness)
• known hypersensitivity, intolerance, or unresponsiveness to risperidone.

Contacts and Locations

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Sponsors and Collaborators

Janssen-Ortho Inc., Canada

Investigators

Study Director:	Janssen-Ortho Inc. Clinical Trial	Janssen-Ortho Inc., Canada

More Information

Go to 

Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Publications of Results:

Shea S, Turgay A, Carroll A, Schulz M, Orlik H, Smith I, Dunbar F. Risperidone in the treatment of disruptive behavioral symptoms in children with autistic and other pervasive developmental disorders. Pediatrics. 2004 Nov;114(5):e634-41. Epub 2004 Oct 18.

ClinicalTrials.gov Identifier:	NCT00261508 History of Changes
Other Study ID Numbers:	CR006106
First Posted:	December 5, 2005
Last Update Posted:	January 24, 2011
Last Verified:	January 2011

Keywords provided by Janssen-Ortho Inc., Canada:

Risperidone; child development disorders; pervasive development disorders; autistic disorder	autism; developmental disabilities; antipsychotropic agents

Additional relevant MeSH terms:

Syndrome; Rett Syndrome; Asperger Syndrome; Disease; Autistic Disorder; Developmental Disabilities; Autism Spectrum Disorder; Child Development Disorders, Pervasive; Pathologic Processes; Neurodevelopmental Disorders; Mental Disorders; Mental Retardation, X-Linked; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations

Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Heredodegenerative Disorders, Nervous System; Risperidone; Serotonin Antagonists; Serotonin Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Antipsychotic Agents; Tranquilizing Agents; Central Nervous System Depressants; Psychotropic Drugs; Dopamine Antagonists