Safety and Effectiveness of D-Cycloserine in Children With Autism

Autistic Disorder Clinical Trial

Official title:

A Randomized Controlled Trial of D-Cycloserine in Autism

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00198120
• Other study ID #: K23MH068627
• Secondary ID: K23MH0686270305-
• Status: Completed
• Phase: Phase 3
• First received: September 12, 2005
• Last updated: April 8, 2016
• Start date: February 2004
• Est. completion date: August 2010

Study information

• Verified date: April 2016
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 80
• Est. completion date: August 2010
• Est. primary completion date: September 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 3 Years to 12 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Autistic Disorder

Intervention

Drug:
• D-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
• Placebo
Placebo: same dosing schedule and capsule strength

Locations

Country	Name	City	State
United States	Riley Hospital for Children, Christian Sarkine Autism Treatment Center	Indianapolis	Indiana

Sponsors (4)

Lead Sponsor	Collaborator
Indiana University	Indiana University School of Medicine, National Alliance for Research on Schizophrenia and Depression, National Institute of Mental Health (NIMH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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.	No
Primary	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	No