Evaluating the Effectiveness of Aripiprazole and D-Cycloserine to Treat Symptoms Associated With Autism

Indiana University

Status and phase: Completed; Phase 3

Conditions: Autistic Disorder

Treatments: Drug: Aripiprazole; Drug: D-cycloserine; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00198107

R01MH072961 (U.S. NIH Grant/Contract)

DSIR 82-SEDR

Details and patient eligibility

About

This study will determine the effectiveness of aripiprazole and D-Cycloserine in treating symptoms associated with autism in children.

Full description

Autism is a developmental disorder that affects every child differently. A wide range of symptoms accompany autism, including self-injurious behavior, aggression, and severe tantrums. Despite an improved ability to reduce these symptoms, existing drug treatments continue to be associated with adverse side effects. Also, there is no existing drug treatment that reliably improves social behavior, a core deficit in autism. Studies on drug treatment combinations that are designed to reduce self-injurious behavior, aggression, and severe tantrums and improve social behavior in children with autism have yet to be conducted. This study will address the above-mentioned limitations by evaluating aripiprazole in reducing self-injurious behavior, aggression, and severe tantrums and by evaluating the addition of D-Cycloserine in improving social behavior among children with autism.

This study will include three phases and an add-on component for some children. Participants will be randomly assigned to receive either aripiprazole or a placebo treatment for 8 weeks. Assessments measuring irritability, behavior, and social skills will be conducted at the end of this first phase. Those patients who respond well to aripiprazole will continue to receive aripiprazole treatment for another 16 weeks. This second phase will determine whether aripiprazole is associated with long-term maintenance of symptomatic improvement in patients who respond well to short-term treatment. Assessments will again be conducted at the end of this 16-week period. Those patients whose symptoms have stabilized and continue to improve while on aripiprazole will be asked to participate in the final phase of this study. During the this pilot phase, D-Cycloserine will be added to ongoing treatment with aripiprazole. Patients will take both aripiprazole and D-Cycloserine for an additional 8 weeks to determine if this combination of drug treatments results in improved social behavior once patients' aggression and self-injurious behavior have been stabilized with aripiprazole. At the end of this 8-week period, participants will be assessed for any changes in behavior, irritability, or social skills. Results from this study may aid in developing safer and more effective drug treatments for children and adolescents with autism.

Enrollment: 81 patients

Sex: All

Ages: 5 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Weight of at least 15 kg (33.75 lbs)
• Meets DSM-IV criteria for autistic disorder
• Outpatient
• Medication-free for at least 2 weeks prior to baseline for all psychotropic medications. More information about this criterion, including exceptions, can be found in the protocol.
• Clinical Global Impression Scale Severity score (CGI-S) of at least 4
• Irritability subscale of the Aberrant Behavior Checklist (ABC) score of at least 18
• An IQ of at least 35 or a mental age of at least 18 months
• In good physical health

Exclusion criteria

• Meets DSM-IV criteria for Asperger's disorder, Rett's disorder, childhood disintegrative disorder, any other pervasive developmental disorder (PDD), schizophrenia, psychotic disorder, or bipolar disorder
• Current or past history of alcohol or other substance abuse within 6 months of study entry
• Comorbid neurodevelopmental disorder with possible association to autism (e.g., fragile-X syndrome, tuberous sclerosis)
• A significant medical condition such as heart, liver, kidney, or lung disease, or a seizure disorder
• Pregnant
• Prior adequate use of aripiprazole. More information about this criterion can be found in the protocol.
• Evidence of hypersensitivity to aripiprazole
• History of neuroleptic malignant syndrome

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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81 participants in 3 patient groups, including a placebo group

1 Placebo

Placebo Comparator group

Description:

Participants will take placebo

Treatment:

Drug: Placebo

2 Aripiprazole

Active Comparator group

Description:

Participants will take aripiprazole

Treatment:

Drug: Aripiprazole

3 Aripiprazole + D-cycloserine

Active Comparator group

Description:

Participants first will take aripiprazole then will also take D-cycloserine

Treatment:

Drug: D-cycloserine

Drug: Aripiprazole