Safety and Effectiveness of D-Cycloserine in Children With Autism

This project proposes to study the efficacy and safety of D-cycloserine in children with
autism. The central hypothesis of this project is that D-cycloserine will be efficacious in
reducing certain symptoms of autism including some aspects of social impairment.

Autism is a severe neuropsychiatric disorder with a prevalence of at least 0.1 %. Despite
investigations into the pharmacologic treatment of autism, no drugs have been shown to
consistently improve the core symptoms of the disorder, namely social and communication
impairment. Pilot data has suggested that D-cycloserine, a drug that affects the
N-methyl-D-aspartate (NMDA) subtype of glutamate receptor, has efficacy for the symptom of
social withdrawal in autism. In this study, children with autism will be randomly assigned
to treatment with either D-cycloserine or placebo for 8 weeks. Both the subjects and
investigators will be blind to treatment assignment. Subjects will be rated on a variety of
clinical measures to examine the effects of D-cycloserine on social withdrawal and other
symptoms of autism. Safety data including side-effects, vital signs, blood tests, and
electrocardiograms will be performed at the beginning and end of the study. This study will
provide important information about the effects of D-cycloserine for treating core and
associated symptoms of autism. It will also greatly expand the knowledge about glutamatergic
agents in autism and provide crucial information regarding the pathophysiology and future
design of drug studies in autism.

Inclusion Criteria:

- Age 3 Years to 12 Years

- Diagnostic Statistical Manual Version -IV (DSM-IV) and Autism Diagnostic Interview -
Revised (ADI-R)-confirmed Diagnosis of Autistic Disorder

- Aberrant Behavior Checklist (ABC) Lethargy Subscale Score of 13 or greater

Exclusion Criteria:

- Children with Severe to Profound Mental Retardation

- Weight at Screening Visit <11 kilograms

- Clinical Global Impressions-Severity Score of 7

- Presence of a Neurodevelopmental Disorder with Possible Associations to Autism:
Subjects with Fragile X Syndrome, Tuberous Sclerosis, or other neurodevelopmental
disorders known to be associated with autism or autistic features will be excluded.

- Presence of a Psychiatric Disorder that would Require a Specific Type of Treatment:
Subjects with major depressive disorder, bipolar disorder, or a psychotic disorder
will be excluded because treatment for these disorders often requires specific
psychotropic agents. Subjects with an active substance use disorder will be excluded
because of safety concerns and problems this would cause in assessing efficacy.

- Presence of a Medical Condition that would make Treatment with D-Cycloserine Less
Safe: Subjects with significant cardiac, hepatic, or renal disease will be excluded
due to concerns about pharmacokinetic alterations or adverse effects. Subjects with
epilepsy or a history of seizures will be excluded due to rare reports of seizures
with high doses of D-cycloserine. D-cycloserine is an U.S. FDA Pregnancy Category C
drug. Because of the unknown effects of D-cycloserine on the developing human fetus,
females of childbearing potential will be given a urine pregnancy test and required
to use a suitable form of birth control during the study.