Clinical trial NCT00198120: Safety and Effectiveness of D-Cycloserine in Children With Autism
Official title: A Randomized Controlled Trial of D-Cycloserine in Autism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Autistic Disorder
Keywords: Autistic Disorder
cycloserine
pharmacology
glutamatergic agents
communication
social interaction
Double-Blind Method
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
name: National Alliance for Research on Schizophrenia and Depression
name: Indiana University School of Medicine
First posted: 2005-09-20
Enrollment: 80
Sex: ALL
Minimum age (years): 3
Maximum age (years): 12
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Clinical Global Impressions (CGI) Global Improvement
timeFrame: Change from Baseline at 8 Weeks
measure: Change in Clinical Global Impressions (CGI) Global Improvement
timeFrame: Change from Open-Label Baseline at 8 Weeks
measure: Change in Lethargy Subscale of the Aberrant Behavior Checklist (ABC)
timeFrame: Change from Baseline at 8 Weeks.
measure: Change in Lethargy Subscale of the Aberrant Behavior Checklist (ABC)
timeFrame: Change from Open-Label Baseline at 8 Weeks
Secondary outcomes:
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 School of Medicine
name: Christopher J. McDougle, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Aye SZ, Ni H, Sein HH, Mon ST, Zheng Q, Wong YKY. The effectiveness and adverse effects of D-cycloserine compared with placebo on social and communication skills in individuals with autism spectrum disorder. Cochrane Database Syst Rev. 2021 Feb 14;2(2):CD013457. doi: 10.1002/14651858.CD013457.pub2.