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Safety and Effectiveness of D-Cycloserine in Children With Autism

This study has been completed.
Sponsor:
Collaborators:
National Institute of Mental Health (NIMH)
National Alliance for Research on Schizophrenia and Depression
Indiana University School of Medicine
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT00198120
First received: September 12, 2005
Last updated: April 8, 2016
Last verified: April 2016
  Purpose
This study will determine the effectiveness of D-cycloserine in reducing symptoms of autism in autistic children.

Condition Intervention Phase
Autistic Disorder
Drug: D-cycloserine
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized Controlled Trial of D-Cycloserine in Autism

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Change in Clinical Global Impressions (CGI) Global Improvement [ Time Frame: Change from Baseline at 8 Weeks ] [ Designated as safety issue: No ]
    All randomized subjects in the Double-Blind Phase will be assessed for change.

  • Change in Clinical Global Impressions (CGI) Global Improvement [ Time Frame: Change from Open-Label Baseline at 8 Weeks ] [ Designated as safety issue: No ]
    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) [ Time Frame: Change from Baseline at 8 Weeks. ] [ Designated as safety issue: No ]
    All randomized subjects in the Double-Blind Phase will be assessed for change.

  • Change in Lethargy Subscale of the Aberrant Behavior Checklist (ABC) [ Time Frame: Change from Open-Label Baseline at 8 Weeks ] [ Designated as safety issue: No ]
    All placebo non-responders will enter into an open-label phase after the Double-Blind Phase


Enrollment: 80
Study Start Date: February 2004
Study Completion Date: August 2010
Primary Completion Date: September 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   3 Years to 12 Years   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00198120

Locations
United States, Indiana
Riley Hospital for Children, Christian Sarkine Autism Treatment Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University
National Institute of Mental Health (NIMH)
National Alliance for Research on Schizophrenia and Depression
Indiana University School of Medicine
Investigators
Principal Investigator: Christopher J. McDougle, MD Indiana University School of Medicine
  More Information

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00198120     History of Changes
Other Study ID Numbers: K23MH068627  0305-30  DDTR BK-TKND 
Study First Received: September 12, 2005
Last Updated: April 8, 2016
Health Authority: United States: Institutional Review Board

Keywords provided by Indiana University:
Autistic Disorder
cycloserine
pharmacology
glutamatergic agents
communication
social interaction
Double-Blind Method

Additional relevant MeSH terms:
Autistic Disorder
Child Development Disorders, Pervasive
Neurodevelopmental Disorders
Mental Disorders
Cycloserine
Anti-Infective Agents, Urinary
Anti-Infective Agents
Renal Agents
Antibiotics, Antitubercular
Antitubercular Agents
Anti-Bacterial Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on December 05, 2016