Pharmacogenomics in Autism Treatment
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.
For this study, we will identify 40 children (4 to 18 years old) with autism who also have serious behavioral problems. We will then treat them with risperidone. Blood samples will be obtained prior to treatment and at eight weeks of treatment or study exit. At that time, efficacy will be assessed using the Clinical Global Impression-Improvement scale (CGI-I) and the Irritability subscale of the Aberrant Behavior Checklist (ABC). Blood genomic profiles before and after risperidone treatment will be determined using Affymetrix oligonucleotide microarrays combined with RT-PCR.
Blood genomic profiles are shown to predict medication response for disorders such as cancer and epilepsy. This exploratory or discovery study will use blood genomic profiles before and after risperidone treatment in children with autism and severe behavioral difficulties to determine if the profiles can predict response to treatment. The ultimate goal of this line of research is to develop methods to predict which medications work for which child before initiating treatment, to predict which child might develop particular side effects, and to identify new treatment targets for future medication development.
Risperidone will be started at 0.5 mg at bedtime for 4 days and, if the current dosage is tolerated as evidenced by no more than mild sedation, no EPS or other moderate to severe AEs, and if there are continued behavioral symptoms, the dose will be increased to 1 mg at bedtime for an additional 4 days. If tolerated and indicated, 0.5 mg will be added in the AM for a daily total of 1.5 mg. After that, dosages may be increased if there does not appear to be an adequate clinical response. Dosage will not be increased if there are side effects (e.g. excessive sedation, salivation, EPS, lactation) and may be decreased if it is not tolerated. If the investigator determines that a significant adverse reaction occurs or if the subject or his or her family wants to stop the study, the medication will be tapered or stopped depending on the dose and reason for stopping and the subject will be offered alternative treatment at the M.I.N.D. Institute Clinic or referred elsewhere. This dosing schedule mirrors that used in the two recent positive trials of risperidone for treating severe behavioral problems in autism (McCracken et al., 2002; Shea et al., 2004).
Control: Uncontrolled, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
UC San Francisco
University of California, San Francisco
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00584701
- Information obtained from ClinicalTrials.gov on December 16, 2010
Medical and Biotech [MESH] Definitions
A childhood disorder predominately affecting boys and similar to autism (AUTISTIC DISORDER). It is characterized by severe, sustained, clinically significant impairment of social interaction, and restricted repetitive and stereotyped patterns of behavior. In contrast to autism, there are no clinically significant delays in language or cognitive development. (From DSM-IV)
A selective blocker of DOPAMINE D2 RECEPTORS and SEROTONIN 5-HT2 RECEPTORS that acts as an atypical antipsychotic agent. It has been shown to improve both positive and negative symptoms in the treatment of SCHIZOPHRENIA.
The purpose of this study is to evaluate the effectiveness (change in level of irritability and related behaviors) and safety and tolerability of the administration of 2 different fixed do...
The purpose of this study is to investigate brain development in autism by longitudinally assessing children with autism, as well as typically developing controls, using advanced MR techni...
This is an eight-week open-label randomized parallel group clinical trial focusing on the comparison of risperidone alone with risperidone plus valproate among hospitalized adult patients...
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 a...
The purpose of this study is to determine whether CM-AT is safe and effective in treating the core symptoms of autism.
Children with autism spectrum disorders (ASDs) often have severe behavioral problems. Not all children with these problems respond to atypical antipsychotic medications; therefore, we investigated whe...
Efficacy and safety of 2 risperidone doses were evaluated in children and adolescents with autism. Patients (N = 96; 5-17 years), received risperidone (low-dose: 0.125 mg/day [20 to 45 kg] or hig...
Autism, a neurodevelopmental disorder, is characterized by abnormal social interactions, impaired social communication and repetitive behaviors and/or restricted interests, along with several associat...
Ginkgo biloba has been reported to affect the neurotransmitter system and to have antioxidant properties that could impact the pathogenesis of Autism Spectrum Disorder. Based on these studies, we deci...
Autism is a neurodevelopmental disorder that causes significant impairment in socialization and communication. It is also associated with ritualistic and stereotypical behaviour. Recent studies propos...