Safety and Effectiveness of D-Cycloserine in Children With Autism

Study Overview
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Brief Summary
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This study will determine the effectiveness of D-cycloserine in reducing symptoms of autism in autistic children.

Detailed Description
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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.

Official Title
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A Randomized Controlled Trial of D-Cycloserine in Autism

Conditions
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Autistic Disorder

Intervention / Treatment
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* Drug: D-cycloserine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 3 Years
Maximum Age: 12 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Participants will receive D-Cycloserine for 8 weeks. | Drug: D-cycloserine<br>* 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<br>* Other names: Cycloserine;|
| Placebo Comparator: 2<br>Participants will receive placebo for 8 weeks. | Drug: Placebo<br>* Placebo: same dosing schedule and capsule strength<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Clinical Global Impressions (CGI) Global Improvement | All randomized subjects in the Double-Blind Phase will be assessed for change. | Change from Baseline at 8 Weeks | 
| Change in Clinical Global Impressions (CGI) Global Improvement | All placebo non-responders will enter into an open-label phase after the Double-Blind Phase | Change from Open-Label Baseline at 8 Weeks | 
| Change in Lethargy Subscale of the Aberrant Behavior Checklist (ABC) | All randomized subjects in the Double-Blind Phase will be assessed for change. | Change from Baseline at 8 Weeks. | 
| Change in Lethargy Subscale of the Aberrant Behavior Checklist (ABC) | All placebo non-responders will enter into an open-label phase after the Double-Blind Phase | Change from Open-Label Baseline at 8 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Autistic Disorder, cycloserine, pharmacology, glutamatergic agents, communication, social interaction, Double-Blind Method