Treatment of Autism in Children and Adolescents
Condition: Autistic Disorder
MeSH terms: Autistic Disorder
Study type: Interventional
Phase: Phase 3

Summary: 
      This study is designed to determine the effectiveness of risperidone, a drug treatment for
      the interfering symptoms of Autistic Disorder in children and adolescents between the ages of
      5 and 17. Between 100 and 120 patients will be participating in this research study at five
      academic medical centers in the United States. The primary aim of the treatment is to reduce
      impairing behavioral symptoms such as aggression, explosive outbursts, or self-injurious
      behavior, without significant side effects. A secondary aim is to evaluate possible
      improvement in the level of social relatedness, attention, motor coordination, and short-term
      memory.

      This study is a placebo-controlled, double-blind study (neither the investigators nor
      patients know if the treatment being given is risperidone or an inactive substance, placebo).
      Patients will be asked to participate for 6 to 8 months. For the first 8 weeks, patients will
      receive either risperidone or placebo, randomly chosen. At the end of the 8 weeks, those
      patients who have improved and were on risperidone will be asked to continue on this
      medication for another 4 months. The last two months of the study are again double-blind
      (neither patients nor investigators know treatment). Patients will either continue
      risperidone treatment or be gradually tapered from risperidone (placebo-substitution). This
      blinded discontinuation phase will last 2 months during which patients will be closely
      monitored for recurrence or worsening of symptoms. Patients who have been treated with
      placebo in the first 8 weeks of the study and have not improved will be treated with
      risperidone. Weekly visits are required for the first 8 weeks of the study, monthly visits
      for the following 4 months, and weekly visits during the last 2 months of the study.
    

Detailed description: 
      The primary purpose of this study is to compare the relative safety and efficacy of
      risperidone and placebo in the treatment of children and adolescents with autistic disorder.

      HYPOTHESES: (1) Risperidone will be more effective than placebo in reducing impulsive
      aggression, agitation, self-injurious behavior, and troublesome repetitive behavior
      associated with autism. (2) Risperidone will result in more sedation (transient) and weight
      gain than placebo. (3) Patients continued on risperidone will be significantly less likely to
      experience exacerbation of symptoms of irritability, aggression, agitation, and stereotypy
      than those randomized to placebo, as measured by the Aberrant Behavior Checklist (ABC), the
      Ritvo-Freeman Real Life Rating Scale, and the compulsions scale from the Children's
      Yale-Brown Obsessive Compulsive Scale (CY-BOCS). (4) Patients continued on risperidone would
      show superior adjustment and functioning at the end of the trial, as evidenced by lower
      Clinical Global Impression ratings, when compared to patients randomized to placebo.

      Design Phase I: Double-Blind Phase - Randomized, double-blind, placebo-controlled, parallel
      groups design. Eight-week double-blind treatment with risperidone or placebo. Eight-week open
      trial with risperidone for placebo non-responders (patients who were randomized to placebo
      and showed no improvement).

      (Risperidone responders will be eligible to enter the four-month extension study. Placebo
      responders and risperidone non-responders will be managed as clinically appropriate by each
      research site.) Phase II: Extension Study - Four-month, open treatment with risperidone. Dose
      adjustment permitted according to clinical assessment (efficacy or adverse events).
      Two-month, randomized, double-blind, placebo-controlled discontinuation, parallel group
      design.

      Completers of four-month Extension Phase protocol who have maintained significantly improved
      status (decrease greater than 25% in ABC from Protocol I Baseline ratings and CGI of much or
      very much improved) will be randomized at the end of four months to placebo substitution or
      risperidone continuation. Group assigned to placebo substitution will undergo weekly blinded
      reductions of entry dose (dosage at end of Phase I) by 25% per week over three consecutive
      weeks. After full placebo substitution, placebo group will remain on placebo for total of up
      to 5 weeks (three-week taper, five-week remaining on placebo). Group assigned to continued
      active treatment will be maintained on entry dose level for full 8 weeks of Phase II,
      assuming no behavioral deterioration. Active treatment patients may have dose reduced for
      treatment emergent effects.

      Randomization - Balanced within site by Tanner Stage (pre-pubertal: Tanner I or II as
      measured by the absence of pubic hair; post-pubertal: Tanner III or greater), gender, and
      anticonvulsant use.
    

Intervention name(s): Risperidone
Intervention type(s): Drug
Intervention MeSH terms: Risperidone
Allocation: Randomized
Masking: Double
Primary purpose: Treatment
Keywords: Autistic Disorder; Risperidone