Safety and Effectiveness of D-Cycloserine in Children With Autism

April 8, 2016 updated by: Indiana University

A Randomized Controlled Trial of D-Cycloserine in Autism

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Riley Hospital for Children, Christian Sarkine Autism Treatment Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 years to 12 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Clinical Global Impressions (CGI) Global Improvement
Time Frame: Change from Baseline at 8 Weeks
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
Time Frame: 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 from Open-Label Baseline at 8 Weeks
Change in Lethargy Subscale of the Aberrant Behavior Checklist (ABC)
Time Frame: Change from Baseline at 8 Weeks.
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)
Time Frame: 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 from Open-Label Baseline at 8 Weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Christopher J. McDougle, MD, Indiana University School of Medicine

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2004

Primary Completion (Actual)

September 1, 2007

Study Completion (Actual)

August 1, 2010

Study Registration Dates

First Submitted

September 12, 2005

First Submitted That Met QC Criteria

September 12, 2005

First Posted (Estimate)

September 20, 2005

Study Record Updates

Last Update Posted (Estimate)

April 12, 2016

Last Update Submitted That Met QC Criteria

April 8, 2016

Last Verified

April 1, 2016

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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