Clinical trial NCT01086475: D-Cycloserine and Social Skills Training in Autism Spectrum Disorders
Official title: A Randomized, Placebo-Controlled Trial of D-Cycloserine for the Enhancement of Social Skills Training in Pervasive Developmental Disorders
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Autistic Disorder
Asperger's Disorder
Pervasive Developmental Disorder NOS
Keywords: Autism Spectrum Disorder
D-cycloserine
Social Skills Training
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: United States Department of Defense
First posted: 2010-03-15
Enrollment: 68
Sex: ALL
Minimum age (years): 5
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Detailed description: This study will evaluate the efficacy of D-Cycloserine given 30 minutes prior to each of 10 weekly Social Skills Training Sessions for the treatment of social impairment in children (ages 5-11 years) with PDD during a randomized placebo-controlled trial. This will examine our central hypothesis that D-cycloserine will enhance learning of social skills in children with PDD's.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Social Responsiveness Scale (SRS) Change
timeFrame: Completed at Baseline and Week 11
measure: Social Responsiveness Scale (SRS) at Follow-Up
timeFrame: Completed at Week 22
Secondary outcomes:
measure: Clinical Global Impressions Improvement Scale Responder Analysis
timeFrame: Week 11
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Riley Hospital for Children
state: Indiana
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
Study officials:
affiliation: Indiana University School of Medicine
name: Noha F. Minshawi, Ph.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Craig A. Erickson, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.