A Phase 2/3 interventional study of Risperidone in Autism, sponsored by University of California, San Francisco. Completed at 1 site in United States. Open to participants aged 4 Years to 18 Years. Per ClinicalTrials.gov, last updated 2012-07-24.
Sponsored by University of California, San Francisco · Phase 2/3, Interventional, and 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).
1,344 studies on the registry are indexed under Autistic Disorder; 334 are open to participants now.
This study's enrollment of 49 is close to the median of 45 across 1,044 interventional studies indexed under Autistic Disorder.
Browse Autistic Disorder studies →University of California, San Francisco is the lead sponsor of 2,132 studies on the registry; 375 are open to participants now.
Of its 262 completed or terminated interventional studies of FDA-regulated products, 196 (75%) have results posted.
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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.
Exclusion Criteria:
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
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
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.
Time frame: Baseline, 8 weeks
Exon Expression Positively or Negatively Correlated With Percentage Improvement in ABC-I
Affymetrix GeneChip Human Exon 1.0 ST Arrays (Affymetrix, Santa Clara, CA, USA) were used to obtain gene expression values. Raw data (Affymetrix.CEL files) was imported into Partek Genomics Suite 6.4 (Partek, St Louis, MO, USA). Probe summarization and probe set normalization were performed using robust multichip average, which included background correction, quantile normalization, log2 transformation and median polish probe set summarization. Exons in genes correlated with percentage improvement on the Aberrant Behavior Checklist Irritability subscale were identified.
Time frame: Baseline, 8 Weeks
Participants recruitment at the UCDavis MIND Institute from the local community.
| Milestone | Active Risperidone |
|---|---|
| Started | 49 |
| Completed | 46 |
| Not completed | 3 |
| Milestone | Active Risperidone |
|---|---|
| Started | 46 |
| Completed | 34 |
| Not completed | 12 |
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.
| percent change in scores | Active Risperidone |
|---|---|
| Percent Change of ABC - Irritability Subscale Score | -44.5 (-95.0 to 6) |
Affymetrix GeneChip Human Exon 1.0 ST Arrays (Affymetrix, Santa Clara, CA, USA) were used to obtain gene expression values. Raw data (Affymetrix.CEL files) was imported into Partek Genomics Suite 6.4 (Partek, St Louis, MO, USA). Probe summarization and probe set normalization were performed using robust multichip average, which included background correction, quantile normalization, log2 transformation and median polish probe set summarization. Exons in genes correlated with percentage improvement on the Aberrant Behavior Checklist Irritability subscale were identified.
| Number of Correlated Genes | Risperidone |
|---|---|
| Exon Expression Positively or Negatively Correlated With Percentage Improvement in ABC-I | 5 |
Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Active Risperidone | — | 0/49 (0%) | 0/49 (0%) |
| Age, Categorical(Participants) | Active Risperidone |
|---|---|
| <=18 years | 49 |
| Between 18 and 65 years | 0 |
| >=65 years | 0 |
| Age Continuous(years) | Active Risperidone |
|---|---|
| Mean | 9.4 ± 4.3 |
| Sex: Female, Male(Participants) | Active Risperidone |
|---|---|
| Female | 9 |
| Male | 40 |
| Region of Enrollment(participants) | Active Risperidone |
|---|---|
| United States | 49 |
This study is completed, as verified in Jun 2012. You cannot join it, but the record below documents what was studied.
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University of California, San Francisco