Clinical trial NCT01333072: Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART)
Official title: Biomarkers in Autism of Aripiprazole and Risperidone Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Autistic Disorder
Keywords: Autistic Disorder
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
First posted: 2011-04-11
Enrollment: 80
Sex: ALL
Minimum age (years): 6
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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. Although the FDA has approved use of the antipsychotic drug risperidone 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in the Irritability Subscale of the Larger ABC (Abberent Behavior Checklist) That Occur From Baseline to 10 Weeks
timeFrame: baseline to 10 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: C. Lindsay DeVane, Pharm.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: DeVane CL, Charles JM, Abramson RK, Williams JE, Carpenter LA, Raven S, Gwynette F, Stuck CA, Geesey ME, Bradley C, Donovan JL, Hall AG, Sherk ST, Powers NR, Spratt E, Kinsman A, Kruesi MJ, Bragg JE Jr. Pharmacotherapy of Autism Spectrum Disorder: Results from the Randomized BAART Clinical Trial. Pharmacotherapy. 2019 Jun;39(6):626-635. doi: 10.1002/phar.2271. Epub 2019 May 29.