D-Cycloserine and Social Skills Training in Autism Spectrum Disorders

• Sponsor: Indiana University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01086475
• Collaborator: United States Department of Defense (U.S. Fed)
• Enrollment: 68
• Locations: 2
• Arms: 2
• Duration (Months): 46.1
• Patients Per Site: 34
• Patients Per Site Per Month: 0.7

Study Details

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
• 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: Mar 1, 2010
• Actual Primary Completion Date: Jan 1, 2014
• Actual Study Completion Date: Jan 1, 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 Names: 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 Names: Sugar pill

Outcome Measures

Primary Outcome Measures

1. Social Responsiveness Scale (SRS) Change [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 [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 [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

Criteria

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

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

	Site	City	State	Country	Postal Code
1	Riley Hospital for Children	Indianapolis	Indiana	United States	46202
2	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Indiana University
• ClinicalTrials.gov Identifier: NCT01086475
• Other Study ID Numbers: 0906-09
• First Posted: Mar 15, 2010
• Last Update Posted: Apr 14, 2016
• Last Verified: Mar 1, 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; Cycloserine

Study Results

Participant Flow

Recruitment Details	Participants were recruited from academic autism treatment centers, local schools, and community organizations.
Pre-assignment Detail	One subject with ASD was excluded from analyses due to early dropout prior to taking the study drug.

Arm/Group Title	D-cycloserine	Placebo
Arm/Group Description	Subjects who received d-cycloserine	Subjects who received placebo
Period Title: Overall Study
STARTED	34	33
COMPLETED	34	33
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	D-cycloserine	Placebo	Total
Arm/Group Description	Subjects randomized to D-cycloserine will be administered 50 mg 30 minutes prior to each of ten Social Skills Training Sessions D-cycloserine: 50 mg dose administered 30 minutes prior to each of the ten Social Skill Training Sessions	Subjects randomized to placebo arm will receive placebo pill 30 minutes prior to each of ten Social Skills Training Sessions Placebo: Placebo pill administered 30 minutes prior to each of the ten Social Skill Training Sessions	Total of all reporting groups
Overall Participants	34	33	67
Age (Count of Participants)
<=18 years	34 100%	33 100%	67 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	8.49 (1.88)	8.34 (1.70)	8.41 (1.78)
Sex: Female, Male (Count of Participants)
Female	6 17.6%	6 18.2%	12 17.9%
Male	28 82.4%	27 81.8%	55 82.1%
Region of Enrollment (participants) [Number]
United States	34 100%	33 100%	67 100%

Outcome Measures

1. Primary Outcome

Title	Social Responsiveness Scale (SRS) Change
Description	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
Time Frame	Completed at Baseline and Week 11

Outcome Measure Data

Analysis Population Description

Each group included up to four children with ASD and two typically-developing peer models (TPs) in the same age group.

Arm/Group Title	D-cycloserine	Placebo
Arm/Group Description	Subjects who received d-cycloserine	Subjects who received placebo
Measure Participants	34	33
Mean (Standard Deviation) [units on a scale]	-13.39 (16.81)	-17.00 (21.33)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D-cycloserine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.45
	Comments
	Method	t-test, 2 sided
	Comments

2. Secondary Outcome

Title	Clinical Global Impressions Improvement Scale Responder Analysis
Description	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.
Time Frame	Week 11

Outcome Measure Data

Analysis Population Description

Each social skills group included up to four children with ASD and two typically-developing peer models (TPs) in the same age group.

Arm/Group Title	D-cycloserine	Placebo
Arm/Group Description	Subjects who received d-cycloserine	Subjects who received placebo
Measure Participants	34	33
Number [percentage of participants]	32.3 95%	33.3 100.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D-cycloserine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.927
	Comments
	Method	Chi-squared
	Comments

3. Primary Outcome

Title	Social Responsiveness Scale (SRS) at Follow-Up
Description	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
Time Frame	Completed at Week 22

Outcome Measure Data

Analysis Population Description

Each group included up to four children with ASD and two typically-developing peer models (TPs) in the same age group.

Arm/Group Title	D-cycloserine	Placebo
Arm/Group Description	Subjects who received d-cycloserine	Subjects who received placebo
Measure Participants	34	33
Mean (Standard Deviation) [units on a scale]	83.5 (2.3)	89.2 (2.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	D-cycloserine, Placebo
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments
	Method	t-test, 2 sided
	Comments

Adverse Events

Time Frame	Data collected at each visit
Arm/Group Title	D-cycloserine		Placebo
Arm/Group Description	Subjects who received d-cycloserine		Subjects who received placebo
All Cause Mortality
	D-cycloserine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	D-cycloserine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/34 (0%)		1/33 (3%)
Psychiatric disorders
Suicidal comment	0/34 (0%)	0	1/33 (3%)	1
Other (Not Including Serious) Adverse Events
	D-cycloserine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	32/34 (94.1%)		28/33 (84.8%)
General disorders
Headache	9/34 (26.5%)	9	7/33 (21.2%)	7
Nasal congestion or Cold	6/34 (17.6%)	6	8/33 (24.2%)	8
Cough	7/34 (20.6%)	7	7/33 (21.2%)	7
Vomiting	6/34 (17.6%)	6	2/33 (6.1%)	2
Increased Motor Activity	1/34 (2.9%)	1	5/33 (15.2%)	5
Interrupted Sleep/Other sleep problems	3/34 (8.8%)	3	5/33 (15.2%)	5
Restlessness/Agitation	4/34 (11.8%)	4	3/33 (9.1%)	3
Sedation/Drowsiness	2/34 (5.9%)	2	6/33 (18.2%)	6
Psychiatric disorders
Aggression	2/34 (5.9%)	2	5/33 (15.2%)	5
Irritability	16/34 (47.1%)	16	15/33 (45.5%)	15
Sadness	5/34 (14.7%)	5	3/33 (9.1%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.