Autistic Disorder
Conditions
Keywords
Autistic Disorder, cycloserine, pharmacology, glutamatergic agents, communication, social interaction, Double-Blind Method
Brief summary
This study will determine the effectiveness of D-cycloserine in reducing symptoms of autism in autistic children.
Detailed description
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.
Interventions
DRUGD-cycloserine
D-Cycloserine 0.6mg/kg/day in week 1 D-Cycloserine 1.1mg/kg/day in week 2 D-Cycloserine 1.7mg/kg/day in week 3-8 Flexible dosing based on response. Capsule Strength: 10mg, 20mg
DRUGPlacebo
Placebo: same dosing schedule and capsule strength
Sponsors
National Institute of Mental Health (NIMH)
National Alliance for Research on Schizophrenia and Depression
Indiana University School of Medicine
Indiana University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
3 Years to 12 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinical Global Impressions (CGI) Global Improvement | Change from Baseline at 8 Weeks | All randomized subjects in the Double-Blind Phase will be assessed for change. |
| Change in Lethargy Subscale of the Aberrant Behavior Checklist (ABC) | Change from Baseline at 8 Weeks. | All randomized subjects in the Double-Blind Phase will be assessed for change. |
Countries
United States
Outcome results
None listed