Safety and Effectiveness of D-Cycloserine in Children With Autism

NCT00198120 | Completed Phase 3 DMC

• 3 other identifiers: K23MH0686270305-30DDTR BK-TKND
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Autistic Disorder

Keywords

Autistic Disorder; cycloserine; pharmacology; glutamatergic agents; communication; social interaction; Double-Blind Method

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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.

• 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

Study Arms (2)

1

EXPERIMENTAL

Participants will receive D-Cycloserine for 8 weeks.

Drug: D-cycloserine

2

PLACEBO COMPARATOR

Participants will receive placebo for 8 weeks.

Drug: Placebo

Interventions

D-cycloserine DRUG

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

Also known as: Seromycin, Cycloserine

1

Placebo DRUG

Placebo: same dosing schedule and capsule strength

2

Eligibility Criteria

• Age: 3 Years - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Indiana University: lead
• National Institute of Mental Health (NIMH): collaborator
• National Alliance for Research on Schizophrenia and Depression: collaborator
• Indiana University School of Medicine: collaborator

Study Sites (1)

Riley Hospital for Children, Christian Sarkine Autism Treatment Center

Indianapolis, Indiana, 46202, United States

Location

Related Publications (2)

• Iffland M, Livingstone N, Jorgensen M, Hazell P, Gillies D. Pharmacological intervention for irritability, aggression, and self-injury in autism spectrum disorder (ASD). Cochrane Database Syst Rev. 2023 Oct 9;10(10):CD011769. doi: 10.1002/14651858.CD011769.pub2.

  PMID: 37811711 DERIVED

• 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.

  PMID: 33583058 DERIVED

MeSH Terms

Conditions

Autistic Disorder; Communication

Interventions

Cycloserine

Condition Hierarchy (Ancestors)

Autism Spectrum Disorder; Child Development Disorders, Pervasive; Neurodevelopmental Disorders; Mental Disorders; Behavior

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Christopher J. McDougle, MD

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2005
• First Posted: September 20, 2005
• Study Start: February 1, 2004
• Primary Completion: September 1, 2007
• Study Completion: August 1, 2010
• Last Updated: April 12, 2016

Record last verified: 2016-04

Locations

US (1)