Pharmacogenomics in Autism Treatment

NCT00584701 | Completed Phase 2 Results DMC

• 2 other identifiers: 200715817-1R21MH080026
• Study Type: interventional
• Target: 49
• Locations: 1 country
• Sites: 1

Brief Summary

Autism is a complex neurodevelopmental disorder that is thought to involve an interaction between multiple and variable susceptibility genes, environmental factors, and epigenetic effects. Great concern has been raised about the marked increase in the prevalence of autism spectrum disorders in the last decade. Risperidone, the most studied atypical antipsychotic used in children, has been shown to improve severe behavioral difficulties in over half of children with autism who have these difficulties. However, not all children with autism and severe behavioral problems respond to risperidone, and for a few, it has significant side effects. Two controlled studies and numerous open-label and long term studies in children with autism spectrum disorders using the atypical antipsychotic risperidone show a significant decrease of associated serious behavioral problems. The use of atypical antipsychotics is of great concern, however, because of their significant side effects and the fact that only two-thirds of children positively respond. Ways to predict response, appropriate dosage and serious side effects are needed.

Conditions

Autism

Outcome Measures

Primary Outcomes (1)

• Percent Change of ABC - Irritability Subscale Score

  Aberrant Behavior Checklist-Irritability (ABC-I)subscale: measure of assessing changes in symptoms of irritability in children with autism (survey that was normed on a developmentally delayed population of children and adults and is usually completed by a parent or caregiver. There are 45 items that are rated on a 4-point scale from "no problem" to "major problem." ABC-I scores ranges from 0 (best) to 45 (worst). A negative change signifies improvement. We measured percent change of ABC-I scores from 8 weeks after risperidone treatment compared to baseline.

  Baseline, 8 weeks

Secondary Outcomes (1)

• Exon Expression Positively or Negatively Correlated With Percentage Improvement in ABC-I

  Baseline, 8 Weeks

Study Arms (1)

Risperidone

EXPERIMENTAL

Risperidone was started at 0.5mg at bedtime for 4 days. If that dosage was tolerated and there were continued behavioral symptoms, the dose was increased to 1mg at bedtime for an additional 4 days. If tolerated and indicated, 0.5mg was added in the morning for a daily total of 1.5 mg.

Drug: Risperidone

Interventions

Risperidone DRUG

Dose will start at 0.5 mg and may be increased throughout the course of the study if no adverse events occur

Also known as: Risperdal

Risperidone

Eligibility Criteria

• Age: 4 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Willingness to participate and written informed consent obtained from parent and when indicated by subject
• Confirmed DSM-IV-TR diagnosis of Autistic Disorder or Asperger's Disorder using the ADOS and the ADI-R, the current gold standards for diagnosing autism spectrum disorders, subject history, and clinical consensus with PI. The ADI-R and ADOS will be administered by research-reliable clinicians, including a clinical psychologist, a certified trainer on the ADOS and the ADI-R
• rated by study clinician as at least "moderate" on the CGI-Severity scale (a rating of ≥ 4) and greater than 18 on the ABC Irritability subscale
• Males or females of any race between 4 and 18 years of age (5) A nonverbal IQ greater than or equal to 55 on the Stanford-Binet:V (6) Women of childbearing potential must use an adequate method of contraception throughout the study.

You may not qualify if:

• Primary diagnosis of bipolar disorder, schizophrenia, or autism spectrum disorder other than Autistic and Asperger's Disorders
• Nonverbal IQ lower than 55 (Stanford-Binet:V)
• History of seizure activity in the past year (active seizures might confuse efficacy ratings)
• fever, infection, metabolic disturbance or any severe medical illness in the past year
• typical or atypical antipsychotic use within 8 weeks of study entry
• Inability of parents or care takers to give informed consent, travel to the visits, administer medication, or arrange for completion of rating scales. Other non-antipsychotic medications and non-pharmacological treatments will be allowed if started at least 2 months prior to the initial screening and must remain constant for the 8 weeks of this study. These treatments will be recorded as will a history of past trials of medications. Prohibiting ongoing treatment would be difficult to justify to parents and to the IRB and would make adequate recruitment for this pilot study difficult.

Sponsors & Collaborators

• University of California, San Francisco: lead
• Janssen, LP: collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

UC San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Conditions

Autistic Disorder

Interventions

Risperidone

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Robert Hendren, DO
• Organization: UCSF

robert.hendren@ucsf.edu

415-476-7198

Study Officials

• Robert L Hendren, DO

  UC San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 22, 2007
• First Posted: January 2, 2008
• Study Start: January 1, 2008
• Primary Completion: May 1, 2009
• Study Completion: May 1, 2009
• Last Updated: July 24, 2012
• Results First Posted: July 24, 2012

Record last verified: 2012-06

Locations

US (1)