D-Cycloserine and Social Skills Training in Autism Spectrum Disorders

• ClinicalTrials.gov Identifier: NCT01086475
• Recruitment Status: Completed
• First Posted: March 15, 2010
• Results First Posted: April 14, 2016
• Last Update Posted: April 14, 2016
• Sponsor: Indiana University
• Collaborator: United States Department of Defense
• Information provided by (Responsible Party): Indiana University

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Autistic Disorder; Asperger's Disorder; Pervasive Developmental Disorder NOS	Drug: D-cycloserine; Drug: Placebo	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 68 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Placebo-Controlled Trial of D-Cycloserine for the Enhancement of Social Skills Training in Pervasive Developmental Disorders
• Study Start Date: March 2010
• Actual Primary Completion Date: January 2014
• Actual Study Completion Date: January 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: D-cycloserine; Subjects randomized to D-cycloserine will be administered 50 mg 30 minutes prior to each of ten Social Skills Training Sessions	Drug: D-cycloserine; 50 mg dose administered 30 minutes prior to each of the ten Social Skill Training Sessions; Other Name: Seromycin
Placebo Comparator: Placebo; Subjects randomized to placebo arm will receive placebo pill 30 minutes prior to each of ten Social Skills Training Sessions	Drug: Placebo; Placebo pill administered 30 minutes prior to each of the ten Social Skill Training Sessions; Other Name: Sugar pill

Outcome Measures

Primary Outcome Measures :

1. Social Responsiveness Scale (SRS) Change [ Time Frame: Completed at Baseline and Week 11 ]

   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

2. Social Responsiveness Scale (SRS) at Follow-Up [ Time Frame: Completed at Week 22 ]

   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

Secondary Outcome Measures :

1. Clinical Global Impressions Improvement Scale Responder Analysis [ Time Frame: Week 11 ]
   The CGI Global Improvement (CGI-I) is a clinician-rate scale designed to take into account all factors to arrive at an assessment of severity and response to treatment, including parent report, parent-rated measures, teacher-rated measures, and clinician-rated measures. The CGI-I is rated from 1 to 7 (1 = very much improved; 2 = much improved; 3 = minimally improved; 4 = no change; 5 = minimally worse; 6 = much worse; 7 = very much worse) at a single time-point. The CGI-I was completed at each visit, but only at week 11 were those subjects classified as "much" or "very much improved" defined as responders and all other classifications will be regarded as non-responders.

Eligibility Criteria

• Ages Eligible for Study: 5 Years to 11 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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.

Contacts and Locations

Locations

United States, Indiana

Riley Hospital for Children

Indianapolis, Indiana, United States, 46202

United States, Ohio

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States, 45229

Sponsors and Collaborators

Indiana University

United States Department of Defense

Investigators

• Principal Investigator: Noha F. Minshawi, Ph.D.; Indiana University School of Medicine
• Principal Investigator: Craig A. Erickson, M.D.; Children's Hospital Medical Center, Cincinnati

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Indiana University
• ClinicalTrials.gov Identifier: NCT01086475
• Other Study ID Numbers: 0906-09
• First Posted: March 15, 2010
• Results First Posted: April 14, 2016
• Last Update Posted: April 14, 2016
• Last Verified: March 2016

Keywords provided by Indiana University:

Autism Spectrum Disorder; D-cycloserine; Social Skills Training

Additional relevant MeSH terms:

Disease; Autism Spectrum Disorder; Autistic Disorder; Developmental Disabilities; Child Development Disorders, Pervasive; Asperger Syndrome; Pathologic Processes; 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