Treatment of Autism in Children and Adolescents

April 16, 2014 updated by: National Institute of Mental Health (NIMH)

Placebo-Controlled Study of Risperidone for the Treatment of Children and Adolescents With Autism and Negative Behavioral Symptoms

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

101

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Los Angeles, California, United States, 90024
        • UCLA
    • Connecticut
      • New Haven, Connecticut, United States, 06520
        • Yale Univ
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana Univ / Riley Hosp for Children
    • Maryland
      • Baltimore, Maryland, United States, 21231
        • Kennedy Krieger Institute
    • Ohio
      • Columbus, Ohio, United States, 43210
        • Ohio State Univ

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Males and females between the ages of 5 and 17 years 2 months.
  • Weight of 15 kg or greater.
  • DSM-IV diagnosis of Autistic Disorder.
  • Inpatient or outpatient.
  • Medication free for at least 2 weeks for all psychotropic medications (4 weeks for fluoxetine or depot neuroleptics).
  • Anticonvulsants used for treatment of seizure disorder permitted if the dosage has been stable for 4 weeks and patient seizure free for at least 6 months.
  • Clinical Global Impression Severity score of at least 4 and a)18 or greater on the Irritability Scale of the Aberrant Behavior Checklist or b) .5 total score on the Ritvo-Freeman scale.
  • Mental age of at least 18 months.
  • Negative pregnancy test

Exclusion Criteria:

  • IQ below 18 months.
  • Females with a positive pregnancy test. - Evidence of a prior adequate trial with risperidone.
  • Evidence of hypersensitivity to risperidone.
  • Past history of neuroleptic malignant syndrome.
  • DSM-IV diagnosis of Pervasive Developmental Disorder other than Autistic Disorder.
  • Significant medical condition such as heart disease, hypertension, liver or renal failure, pulmonary disease, or unstable seizure disorder.
  • Weight less than 15 kg.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Masking: Double

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Mental Health (NIMH)

Investigators

  • Principal Investigator: Michael Aman, Ohio State Univ
  • Principal Investigator: James McCracken, University of California, Los Angeles
  • Principal Investigator: Christopher J McDougle, Indiana Univ / Riley Hosp for Children
  • Principal Investigator: Elaine Tierney, Hugo W. Moser Research Institute at Kennedy Krieger, Inc.
  • Principal Investigator: Fred Volkmar, Yale Univ
  • Benedetto Vitiello, NIMH Coordinator, Natl Institute of Mental Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 1997

Study Completion

February 1, 2001

Study Registration Dates

First Submitted

March 31, 2000

First Submitted That Met QC Criteria

March 31, 2000

First Posted (Estimate)

April 3, 2000

Study Record Updates

Last Update Posted (Estimate)

April 17, 2014

Last Update Submitted That Met QC Criteria

April 16, 2014

Last Verified

August 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • N01 MH70001
  • N01 MH70009
  • N01 MH80011
  • N01 MH70010
  • DSIR CT

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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