Biomarkers in Autism of Aripiprazole and Risperidone Treatment (BAART)

• Sponsor: Medical University of South Carolina (Other)
• Overall Status: Completed
• CT.gov ID: NCT01333072
• Collaborator: (none)
• Enrollment: 80
• Location: 1
• Arms: 2
• Duration (Months): 49
• Patients Per Site Per Month: 1.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Autistic Disorder	Drug: Aripiprazole; Drug: Risperidone	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 80 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Supportive Care
• Official Title: Biomarkers in Autism of Aripiprazole and Risperidone Treatment
• Study Start Date: Jul 1, 2011
• Actual Primary Completion Date: Aug 1, 2015
• Actual Study Completion Date: Aug 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Risperidone Atypical antipsychotic	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).; Other Names: Risperdal
Active Comparator: Aripiprazole Atypical antipsychotic	Drug: 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.; Other Names: Abilify

Outcome Measures

Primary Outcome Measures

1. Changes in the Irritability Subscale of the Larger ABC (Abberent Behavior Checklist) That Occur From Baseline to 10 Weeks [baseline to 10 weeks]

   Multi-center, blinded clinical trial to evaluate biomarkers as predictors of efficacy and safety in children with autistic disorder to risperidone, an atypical antipsychotic drug and aripiprazole, an antipsychotic having a unique clinical and receptor-binding profile. The major outcome measure was the score on the Irritability subscale of the Aberrant Behavior Checklist (ABC-I) . The ABC has 58 items describing some aspect of behavior and the Irritability sub-scale has 15 items, each completed by a parent or caregiver under the supervision of an investigator. Scores on each item range from 0 = no problem and 3 = severe problem (range of total scores 0 to 45). A fall in scores indicates behavioral improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medical University of South Carolina	Charleston	South Carolina	United States	29425

Sponsors and Collaborators

• Medical University of South Carolina

Investigators

• Principal Investigator: C. Lindsay DeVane, Pharm.D., Medical University of South Carolina

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT01333072
• Other Study ID Numbers: R01HD062550-01A1
• First Posted: Apr 11, 2011
• Last Update Posted: Sep 26, 2018
• Last Verified: Sep 1, 2018

• Keywords provided by Medical University of South Carolina: Autistic Disorder
• Additional relevant MeSH terms: Autistic Disorder; Risperidone; Aripiprazole

Study Results

Participant Flow

Recruitment Details	80 participants were enrolled but 19 dropped from the study due to placebo response (16), parent withdrew child (2) and physician withdrew 1 subject. This left 61 subjects for randomization, as specified

Arm/Group Title	Risperidone	Aripiprazole
Arm/Group Description	Atypical antipsychotic 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.	Atypical antipsychotic 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.
Period Title: Overall Study
STARTED	30	31
COMPLETED	24	27
NOT COMPLETED	6	4

Baseline Characteristics

Arm/Group Title	Risperidone	Aripiprazole	Total
Arm/Group Description	Atypical antipsychotic 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).	Atypical antipsychotic 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.	Total of all reporting groups
Overall Participants	30	31	61
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	8.3	8.5	8.4
Sex: Female, Male (Count of Participants)
Female	7 23.3%	6 19.4%	13 21.3%
Male	23 76.7%	25 80.6%	48 78.7%
Region of Enrollment (participants) [Number]
United States	30 100%	31 100%	61 100%

Outcome Measures

1. Primary Outcome

Title	Changes in the Irritability Subscale of the Larger ABC (Abberent Behavior Checklist) That Occur From Baseline to 10 Weeks
Description	Multi-center, blinded clinical trial to evaluate biomarkers as predictors of efficacy and safety in children with autistic disorder to risperidone, an atypical antipsychotic drug and aripiprazole, an antipsychotic having a unique clinical and receptor-binding profile. The major outcome measure was the score on the Irritability subscale of the Aberrant Behavior Checklist (ABC-I) . The ABC has 58 items describing some aspect of behavior and the Irritability sub-scale has 15 items, each completed by a parent or caregiver under the supervision of an investigator. Scores on each item range from 0 = no problem and 3 = severe problem (range of total scores 0 to 45). A fall in scores indicates behavioral improvement.
Time Frame	baseline to 10 weeks

Outcome Measure Data

Analysis Population Description

Score on Aberrant Behavior Checklist (ABC) scale for Irritability

Arm/Group Title	Risperidone	Aripiprazole
Arm/Group Description	Atypical antipsychotic 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).	Atypical antipsychotic 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.
Measure Participants	24	27
Mean (Standard Deviation) [units on a scale]	12.7 (3.0)	14.1 (3.5)

Adverse Events

Arm/Group Title	Risperidone		Aripiprazole
Arm/Group Description	Atypical antipsychotic 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).		Atypical antipsychotic 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.
All Cause Mortality
	Risperidone		Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/31 (0%)
Serious Adverse Events
	Risperidone		Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/30 (0%)		0/31 (0%)
Other (Not Including Serious) Adverse Events
	Risperidone		Aripiprazole
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	23/30 (76.7%)		19/31 (61.3%)
Metabolism and nutrition disorders
weight gain	21/30 (70%)		8/31 (25.8%)
Psychiatric disorders
sedation	2/30 (6.7%)		7/31 (22.6%)
enuresis	0/30 (0%)		4/31 (12.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.