Clinical trial NCT00870727: Study of Aripiprazole in the Treatment of Pervasive Developmental Disorders
Official title: Pharmacotherapy of Pervasive Developmental Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pervasive Developmental Disorder
Keywords: PDD NOS
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: Bristol-Myers Squibb
First posted: 2009-03-27
Enrollment: 33
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: The purpose of this study is to develop a better tolerated and more effective pharmacologic treatment with individuals with Pervasive Developmental Disorder. This is a double-blind, placebo-controlled study of aripiprazole in the management of the maladaptive behaviors of Pervasive Developmental Disorder. The investigators hypothesize that aripiprazole will be more effective than placebo for reducing aggression, tantrum and self-injurious behavior in children with Pervasive Developmental Disorder.

Detailed description: Pervasive developmental disorders (PDDs) are characterized by severe impairments in social interaction and communication in addition to restricted patterns of interests and activities. Research suggests that a dysregulation of the dopamine and serotonin systems contributes to these interfering behaviors in individuals with PDD. After benefits of typical neuroleptics were reported in subjects with PDD, research shifted to the atypical antipsychotics which have been shown to be better tolerated and effective in this population. However, the atypical antipsychotics have also been associated with adverse effects. Thus there remains a need for a novel pharmacotherapy that would be safe and effective for children and adolescents with PDDs. The primary objectives of this study are to determine whether aripiprazole is effective and well tolerated for irritability in children and adolescents with PDD not otherwise specified (NOS) during an 8-week acute phase and whether the effectiveness and tolerability of aripiprazole is maintained during a 16-week continuation phase.

Eligibility criteria: Inclusion Criteria:

* Male and female outpatients between the ages of 5 and 17 years and greater than or equal to 15 kg body weight.
* Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revised (DSM-IV-TR) diagnosis of Pervasive Developmental Disorder Not Otherwise Specified (PDD NOS).
* Psychotropic medication-free for at least 2 days prior to screening laboratory tests and electrocardiogram (ECG).
* Significant irritability as determined by a Clinical Global Impression Severity score of greater or equal to 4 (Moderately ill) and a score of equal to or greater than 18 on the Aberrant Behavior Checklist Irritability Subscale.
* Intelligence quotient (IQ) of equal to or greater than 50 based on the Wechsler Intelligence Scale for Children (WISC), 4th edition; the Leiter International Test of Intelligence-Revised will be used if a child is nonverbal but thought to have an IQ greater than or equal to 50.

Exclusion Criteria:

* DSM-IV-TR diagnosis other than PDD NOS (autistic disorder, Asperger's disorder, Rett's disorder, or childhood disintegrative disorder), schizophrenia, bipolar disorder or substance abuse within the last 6 months.
* Comorbid disorder with possible association to autism (e.g., Fragile X Syndrome, Tuberous Sclerosis).
* A significant medical condition such as heart, liver, renal, or pulmonary disease, or a seizure disorder, as determined by history, physical examination, or laboratory testing.
* Subjects with an active seizure disorder (history of febrile seizures in early childhood will be considered.
* Females with a positive urine pregnancy test.
* Evidence of a prior adequate trial of aripiprazole (defined as equal to or greater than 2 weeks at equal to or greater than 5 mg per day. When there is not evidence of a prior adequate trial, subjects must be medication-free for a least 2 weeks prior to baseline.
* History of neuroleptic malignant syndrome.
* Subjects who, in the opinion of the investigator, are unsuitable in any other way to participate in this study, including being unable to comply with the requirements of the study for any reason.
* Hypersensitivity to aripiprazole \[e.g., allergic response or serious adverse effect\] (significant tachycardia).

Primary outcomes:
measure: Number of Participants Improved as Measured by the Clinical Global Impression-Global Improvement Scale (Improvement Defined as CGI-I=1 or CGI-I=2)
timeFrame: Double-blind phase study exit - up to 8 weeks
measure: Mean Post-baseline Aberrant Behavior Checklist Irritability Subscale Score, Parent Report, Double-blind Phase
timeFrame: Weeks 1, 2, 3, 4, 6 and 8
Secondary outcomes:
measure: Mean Post-baseline Aberrant Behavior Checklist Hyperactivity Subscale Score, Parent Report, Double-blind Phase
timeFrame: Weeks 1, 2, 3, 4, 6 and 8
measure: Mean Post-baseline Aberrant Behavior Checklist Inappropriate Speech Subscale Score, Parent Report, Double-blind Phase
timeFrame: Weeks 1, 2, 3, 4, 6 and 8
measure: Mean Post-baseline Aberrant Behavior Checklist Social Withdrawal Subscale Score, Parent Report, Double-blind Phase
timeFrame: Weeks 1, 2, 3, 4, 6 and 8
measure: Mean Post-baseline Aberrant Behavior Checklist Stereotypy Subscale Score, Parent Report, Double-blind Phase
timeFrame: Weeks 1, 2, 3, 4, 6 and 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
name: Kimberly A. Stigler, MD
role: PRINCIPAL_INVESTIGATOR
References: