Clinical trial NCT00198107: Evaluating the Effectiveness of Aripiprazole and D-Cycloserine to Treat Symptoms Associated With Autism
Official title: Novel Pharmacological Strategies in Autism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Autistic Disorder
Keywords: Children
Adolescents
Aripiprazole
Cycloserine
Aggression
Irritability
Self-Injurious Behavior
Social Interaction
Antipsychotics
Pharmacology
Glutamatergic Agents
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2005-09-20
Enrollment: 81
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Mean Post-baseline Aberrant Behavior Checklist Irritability Score, Parent Report, Double-blind Phase
timeFrame: Weeks 1, 2, 3, 4, 6, and 8
measure: Odds of Improvement as Measured by the Clinical Global Impression-Global Improvement Scale (Improvement Defined as CGI-I=1 or CGI-I=2)
timeFrame: Weeks 1, 2, 3, 4, 6 and 8
Secondary outcomes:
measure: Mean Post-baseline Aberrant Behavior Checklist Hyperactivity Score, Parent Report, Double-blind Phase
timeFrame: Weeks 1, 2, 3, 4, 6 and 8
measure: Mean Post-baseline Aberrant Behavior Checklist Inappropriate Speech Score, Parent Report, Double-blind Phase
timeFrame: Weeks 1, 2, 3, 4, 6, and 8
measure: Mean Post-baseline Aberrant Behavior Checklist Social Withdrawal Score, Parent Report, Double-blind Phase
timeFrame: Weeks 1, 2, 3, 4, 6, and 8
measure: Mean Post-baseline Aberrant Behavior Checklist Stereotypy Score, Parent Report, Double-blind Phase
timeFrame: Weeks 1, 2, 3, 4, 6, and 8
measure: Mean Post-baseline Score on a Modified Version of the Compulsion Subscale of the Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)
timeFrame: Weeks 2, 4, 6 and 8
measure: Mean Vineland Maladaptive Behavior Subscales Total Score, Week 8
timeFrame: Week 8
measure: Mean Autism Diagnostic Observation Schedule (ADOS) Social Affect and Restricted and Repetitive Behaviors Total Score, Week 8
timeFrame: Week 8
measure: Mean Social Reciprocity Scale (SRS) Total Score, Week 8
timeFrame: Week 8
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Riley Hospital for Children, Christian Sarkine Autism Treatment Center
state: Indiana
Study officials:
affiliation: Indiana University School of Medicine
name: Christopher J. McDougle, MD
role: PRINCIPAL_INVESTIGATOR
References: