Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART)

The Biomarkers in autism of aripiprazole and risperidone treatment (BAART) project will
provide evidence-based guidance in the selection and monitoring of drug treatment of autism.
BAART involves 3 academic centers across South Carolina with expertise in phenotyping
patients with autistic spectrum disorders, assessing patient response in clinical trials, and
expertise in pharmacogenomic research. Although the FDA has approved use of the antipsychotic
drugs risperidone and aripiprazole for irritability associated with autistic disorder, a
moderate response rate in pivotal clinical trials and concerns over tolerability and weight
gain can force clinicians to select alternative drug treatments for which evidence-based
support is sparse. BAART will assess predictors of efficacy, tolerability, and safety in 200
children 6-17 years old with autistic disorder (AD) during a double-blind, randomized 10 week
treatment period with either risperidone or aripiprazole. Responders who complete the study
may continue with medication treatment for three months. Factors considered will include 1)
psychiatric history; 2) symptom response; 3) psychosocial support; 4) measures of
tolerability; 5) serum prolactin and brain-derived neurotrophic factor concentration; and 5)
a variety of single nucleotide polymorphisms related to target genes for drug disposition and
transport, response, and tolerability. The BAART project will result in evidence-based
guidelines for selection and monitoring of drug treatment of children and adolescents with
AD.

Inclusion Criteria

- Aged 6 to 17 years and weight of at least 15 kg

- Meet DSM-IV criteria for of AD, established by chart review, clinical judgment and the
Autism Diagnostic Interview- Revised (ADI-R) criteria

- Clinical Global Impressions Severity (CGI-S) score of >4 (moderately ill)

- ABC Irritability subscale score of >18

- Mental age of at least 18 months

- If female and sexually active, must agree to an acceptable method of birth control
during the trial

- Medication free or adequate washout period (2-4 weeks prior to enrollment) of
psychoactive drugs (anticonvulsants permitted for seizure management if dosage is
stable for 4 weeks)

- Parent/guardian able to read and provide informed consent.

Exclusion Criteria

- Psychiatric disorder that is effectively managed by psychoactive medication (e.g.
ADHD, MDD)

- Prior diagnosis or evidence of genetic or other disorder that may interfere with
assessments (e.g. Fragile X syndrome, Fetal alcohol syndrome, history of very low
birth weight) assessed by personal and family history, dysmorphology, and clinical
judgment.

- Prior use of risperidone or aripiprazole for more than 2 weeks

- Seizure during the past 6 months

- History or evidence of a medical condition that would expose them to an undue risk of
a significant adverse event or interfere with assessments during the trial including
but not limited to hepatic, renal, respiratory, cardiovascular, endocrine, hematologic
or immunologic disease as determined by the clinical judgment of the investigator

- Current suicidal or homicidal risk

- Positive urine pregnancy test at baseline

- Dependent on other substances, with the exception of nicotine or caffeine