Safety and Effectiveness of D-Cycloserine in Children With Autism

Sponsor

Indiana University (Other)

Overall Status

Completed

CT.gov ID

NCT00198120

Collaborator

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

Enrollment

Location

Arms

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Autistic Disorder	Drug: D-cycloserine Drug: Placebo	Phase 3

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Randomized Controlled Trial of D-Cycloserine in Autism

Study Start Date :

Feb 1, 2004

Actual Primary Completion Date :

Sep 1, 2007

Actual Study Completion Date :

Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Participants will receive D-Cycloserine for 8 weeks.	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 Other Names: Seromycin Cycloserine
Placebo Comparator: 2 Participants will receive placebo for 8 weeks.	Drug: Placebo Placebo: same dosing schedule and capsule strength

Arm

Intervention/Treatment

Experimental: 1

Participants will receive D-Cycloserine for 8 weeks.

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

Other Names:

Seromycin

Cycloserine

Placebo Comparator: 2

Participants will receive placebo for 8 weeks.

Drug: Placebo

Placebo: same dosing schedule and capsule strength

Outcome Measures

Primary Outcome Measures

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 Clinical Global Impressions (CGI) Global Improvement [Change from Open-Label Baseline at 8 Weeks]
All placebo non-responders will enter into an open-label phase after the Double-Blind Phase
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.
Change in Lethargy Subscale of the Aberrant Behavior Checklist (ABC) [Change from Open-Label Baseline at 8 Weeks]
All placebo non-responders will enter into an open-label phase after the Double-Blind Phase

Eligibility Criteria

Criteria

Ages Eligible for Study:

3 Years to 12 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.