D-Cycloserine and Social Skills Training in Autism Spectrum Disorders

NCT01086475 | Completed Phase 3 Results DMC

• 1 other identifier: 0906-09
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 2

Brief Summary

The purpose of this study is to determine the effectiveness of D-cycloserine for improving social impairment in child with pervasive developmental disorders (PDD).

Conditions

Autistic Disorder; Asperger's Disorder; Pervasive Developmental Disorder NOS

Keywords

Autism Spectrum Disorder; D-cycloserine; Social Skills Training

Outcome Measures

Primary Outcomes (2)

• Social Responsiveness Scale (SRS) Change

  The 65-item SRS is a standardized measure of the core symptoms of autism. Each item is scored on a 4-point Likert scale. The score of each individual item is summed to create a total raw score. A total scores results are as follows: 0-62: Within normal limits 63-79: Mild range of impairment 80-108: Moderate range of impairment 109-149: Severe range of impairment

  Completed at Baseline and Week 11

• Social Responsiveness Scale (SRS) at Follow-Up

  The 65-item SRS is a standardized measure of the core symptoms of autism. Each item is scored on a 4-point Likert scale. The score of each individual item is summed to create a total raw score. A total scores results are as follows: 0-62: Within normal limits 63-79: Mild range of impairment 80-108: Moderate range of impairment 109-149: Severe range of impairment

  Completed at Week 22

Secondary Outcomes (1)

• Clinical Global Impressions Improvement Scale Responder Analysis

  Week 11

Study Arms (2)

D-cycloserine

EXPERIMENTAL

Subjects randomized to D-cycloserine will be administered 50 mg 30 minutes prior to each of ten Social Skills Training Sessions

Drug: D-cycloserine

Placebo

PLACEBO COMPARATOR

Subjects randomized to placebo arm will receive placebo pill 30 minutes prior to each of ten Social Skills Training Sessions

Drug: Placebo

Interventions

D-cycloserine DRUG

50 mg dose administered 30 minutes prior to each of the ten Social Skill Training Sessions

Also known as: Seromycin

D-cycloserine

Placebo DRUG

Placebo pill administered 30 minutes prior to each of the ten Social Skill Training Sessions

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 5 Years - 11 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• DSM-IV-TR diagnosis of autism, Asperger's disorder, or PDD not otherwise specified (NOS) base on a semi-structured review of DSM-IV-R criteria and mental status examination as wll as a complete parental history obtained from the Autism Diagnostic Interview-Revised (ADI-R) and a complete systematic patient interview utilizing the Autism Diagnostic Observation Schedule (ADOS).
• Males and females ages 5-11 years.
• Significant social impairment as evidenced by a parent-rated Social Responsiveness Scale (SRS) T-score of 60 or greater.
• TSSA score of 70% or less on both parent questionnaire and child assessment. Children not showing significant impairment in the four specific social skill areas (greetings/goodbyes, conversations, game play, and understanding emotions) targeted by the SST are less likely to benefit from treatment.
• Communication Standard Score of 70 or greater on the Vineland-II.
• Full Scale IQ greater than 70.
• Subjects must not be taking any psychotropic drugs affecting glutamate neurotransmission (riluzole, memantine, acamprosate, topiramate, amantadine, among others). Subjects may not be taking more than two psychotropic drugs. Dosing of all concomitant psychotropic drugs targeting core social and/or communication impairment must be stable for eight weeks prior to randomization. Dosing of all concomitant psychotropic drugs treating other features associated with pervasive developmental disorders (insomnia, inattention, hyperactivity, anxiety, irritability among others0 must be stable for two weeks (with the exception of four weeks for fluoxetine) prior to randomization.
• Able to participate in group SST based on semi-structured parent and child interview.
• Legal guardian has provided written informed consent and the subject has provided written informed assent. Expectation that a majority of subjects will be able to assent but the potential for the younger children and/or those that are cognitively impaired will not be able to assent.

You may not qualify if:

• Subjects with diagnoses of Rett's disorder or childhood integrative disorder will not be enrolled since these disorders have a different etiology, course, and treatment response. Furthermore, children with these disorders may not function at a high enough level in terms of cognition or language in order to benefit from the SST.
• Initiation of a new psychosocial intervention within 90 days prior to randomization. Participants who have recently had a significant change in their psychosocial interventions will not be eligible until this intervention has been stable for 90 days in order to avoid confounding results of the study. Stable interventions (e.g., speech and occupational therapy), with the exception of concurrent social skills training, will be allowed to continue during the course of the study. Minor changes in ongoing treatment (e.g., missed therapy sessions due to holiday/vacation; planned break in therapy due to school holidays) are not considered significant.
• Subjects exhibiting significant disruptive, aggressive, self-injurious, or sexually inappropriate behavior will not be eligible for enrollment.
• Presence of current DSM-IV-TR psychiatric disorders that require alternative pharmacotherapy or different treatment including psychotic disorders, or major affective disorders, obsessive-compulsive disorder, panic disorder, or substance related disorders.
• Presence of any medical condition that would make treatment with DCS less safe. Subjects with significant cardiac, hepatic, or renal disease will be excluded due to concerns about pharmacokinetic alterations or adverse effects. Subjects with a history of a seizure disorder are permitted if the subject has been seizure free for 6 months and is currently treated with an anticonvulsant that has been stable for 4 weeks. D-Cycloserine is an U.S. FDA Pregnancy Category C drug. Because of the unknown effects of DCS 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. A positive pregnancy test result excludes the subject.
• Presence of any other condition that would make the participants unable to comply with the requirements of the study for any reason.

Sponsors & Collaborators

• Indiana University: lead
• United States Department of Defense: collaborator

Study Sites (2)

Riley Hospital for Children

Indianapolis, Indiana, 46202, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (4)

• 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

• Wink LK, Minshawi NF, Shaffer RC, Plawecki MH, Posey DJ, Horn PS, Adams R, Pedapati EV, Schaefer TL, McDougle CJ, Swiezy NB, Erickson CA. d-Cycloserine enhances durability of social skills training in autism spectrum disorder. Mol Autism. 2017 Jan 25;8:2. doi: 10.1186/s13229-017-0116-1. eCollection 2017.

  PMID: 28138381 DERIVED

• Minshawi NF, Wink LK, Shaffer R, Plawecki MH, Posey DJ, Liu H, Hurwitz S, McDougle CJ, Swiezy NB, Erickson CA. A randomized, placebo-controlled trial of D-cycloserine for the enhancement of social skills training in autism spectrum disorders. Mol Autism. 2016 Jan 14;7:2. doi: 10.1186/s13229-015-0062-8. eCollection 2016.

  PMID: 26770664 DERIVED

MeSH Terms

Conditions

Autistic Disorder; Asperger Syndrome; Child Development Disorders, Pervasive; Autism Spectrum Disorder

Interventions

Cycloserine; Sugars

Condition Hierarchy (Ancestors)

Neurodevelopmental Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Dr. Minshawi
• Organization: Christian Sarkine Autism Treatment Center

nminshaw@iupui.edu

317-944-8162

Study Officials

• Noha F. Minshawi, Ph.D.

  Indiana University School of Medicine

  PRINCIPAL INVESTIGATOR

• Craig A. Erickson, M.D.

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: March 10, 2010
• First Posted: March 15, 2010
• Study Start: March 1, 2010
• Primary Completion: January 1, 2014
• Study Completion: January 1, 2014
• Last Updated: April 14, 2016
• Results First Posted: April 14, 2016

Record last verified: 2016-03

Locations

US (2)