Official Title: “Early Pharmacotherapy Aimed at Neuroplasticity in Autism : Safety and Efficacy”

The purpose of this study is to determine the efficacy, safety, and population pharmacokinetics and determinants of drug responses to buspirone in children with autism using a randomized, double blind, cross over study in children ages 2 to 6 years.

Study Type: Interventional

Study Design: Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Safety/Efficacy Study

Autism is a neurodevelopmental disorder defined as qualitative impairment in social interaction and communication and restrictive stereotype patterns of behavior, interests and activities. Pharmacological agents are being increasingly used off label in very young autistic children, and there is virtually no data regarding the pharmacokinetics, safety or efficacy of these agents in young children.

The approach in this study differs from pharmacotherapy studies of autism carried out thus far in several ways: - the rationale underlying our approach is based upon an attempt to alter synaptic plasticity during postnatal development, focusing on very young children - are integrating our drug trial with a PG study evaluating whether buspirone response is related to expression of genes involved in serotoninergic neurotransmission - will assess these variables together with in vivo assessment of serotonin synthesis capacity with PET.

This is a prospective, randomized, double blind, crossover study where children will be stratified by age into two groups. Treatment will last for 12 weeks with dosing twice a day.

Parent ratings, cognitive tests and blood sampling will occur throughout the study period.

Intervention(s) in this Clinical Trial

• Drug: Buspirone

Primary Measures

• Safety will be measured by obtaining clinical laboratory tests, vital signs and evaluating probably or definitely related adverse events.
• Population pharmacokinetics will be conducted to measure plasma concentrations in relation to the drug responses to buspirone.
• The primary efficacy outcome will be the overall severity score from the Clinical Global Impressions assessment obtained from two raters, (parent and examiner)
• Comparisons of allele, and genotype frequencies between responders and non-responders will be done for each polymorphism using Fisher's exact test to best predict response to buspirone.

Inclusion Criteria:

• Meet study definition for the diagnosis of autistic disorder
• Age 2 to 6 (male or female)
• Informed Consent

Exclusion Criteria:

• Clinical or lab evidence of renal or hepatic disease
• Treatment with any medication known to alter the activity of the CYP3A4 enzyme including ketoconazole, itraconazole, grapefruit juice, erythromycin, clarithromycin, cimetidine, verapamil, diltiazem, rifampin, phenytoin, phenobarbital, or carbamazepine within the previous 3 months
• Use of centrally acting drugs during the 6 weeks prior or during the study
• Presence or history of neurological disorders, including seizure disorders

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 2 Years

Maximum Age for this Clinical Trial: 6 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: National Institute of Child Health and Human Development (NICHD)

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00166621

Study ID Number: PPRU 10659s

ClinicalTrials.gov Identifier: NCT00166621

Health Authority: United States: Federal Government

Pediatric Pharmacology Research Unit Website