Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART)

NCT ID: NCT01333072

Last Updated: 2018-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2015-08-31

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.

Conditions

Autistic Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: QUADRUPLE

Study Groups

Risperidone

Atypical antipsychotic

Group Type: ACTIVE_COMPARATOR

Risperidone

Intervention Type: DRUG

Children weighing 20-45 kg will receive an initial dose of 0.5 mg daily that will be increased to twice daily on day 4 (morning and bedtime). The dosage will be gradually increased in 0.5 mg increments to a maximum dose of 2.5 mg per day (1.0 mg in the morning and 1.5 mg at bedtime) by the fourth treatment week. A slightly accelerated dosage will be allowed for children who weigh more than 45 kg for a maximum dosage of 3.5 mg /day (McCracken et al 2002).

Aripiprazole

Atypical antipsychotic

Group Type: ACTIVE_COMPARATOR

Aripiprazole

Intervention Type: DRUG

The starting dosage will be 2.0 mg/day. The dosage will be allowed to increase to 5.0 mg/day on day 4 and can be increased thereafter as judged clinically appropriate until the maximum dosage of 15 mg/day. The dosage will only be increased in 5.0 mg intervals. No dosage adjustments will be allowed for either drug after 4 weeks.

Interventions

Aripiprazole

The starting dosage will be 2.0 mg/day. The dosage will be allowed to increase to 5.0 mg/day on day 4 and can be increased thereafter as judged clinically appropriate until the maximum dosage of 15 mg/day. The dosage will only be increased in 5.0 mg intervals. No dosage adjustments will be allowed for either drug after 4 weeks.

Intervention Type: DRUG

Risperidone

Children weighing 20-45 kg will receive an initial dose of 0.5 mg daily that will be increased to twice daily on day 4 (morning and bedtime). The dosage will be gradually increased in 0.5 mg increments to a maximum dose of 2.5 mg per day (1.0 mg in the morning and 1.5 mg at bedtime) by the fourth treatment week. A slightly accelerated dosage will be allowed for children who weigh more than 45 kg for a maximum dosage of 3.5 mg /day (McCracken et al 2002).

Intervention Type: DRUG

Other Intervention Names

Abilify; Risperdal

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

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

C. Lindsay DeVane, Pharm.D.

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

References

Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

Reference Type: DERIVED

PMID: 37811711 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31063671 (View on PubMed)

Other Identifiers

R01HD062550-01A1

Identifier Type: NIH

Identifier Source: org_study_id

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