D-Cycloserine Augmentation of Therapy for Pediatric Obsessive-Compulsive Disorder

• ClinicalTrials.gov Identifier: NCT00864123
• Recruitment Status: Completed
• First Posted: March 18, 2009
• Results First Posted: October 17, 2012
• Last Update Posted: October 17, 2012
• Sponsor: University of South Florida
• Information provided by (Responsible Party): Eric Storch, University of South Florida

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Obsessive-compulsive Disorder
• Interventions: Behavioral: Cognitive-behavioral therapy; Drug: D-cycloserine; Drug: Placebo pill
• Enrollment: 30

Participant Flow

Recruitment Details
Pre-assignment Details	Excluded (n = 22) Not interested in participating in study (n=9) Changing medication at Baseline (n=5) Did not receive at least one DCS dose (n = 4) History of adequate CBT course (n=2) Met criteria for comorbid autism (n=1) Did not show up for pre-treatment assessment (n=1)

Arm/Group Title	Cognitive-behavioral Therapy + Placebo	Cognitive-behavioral Therapy + D-cycloserine
Arm/Group Description	Involves receiving cognitive-behavioral treatment of OCD symptoms for 10 sessions. One hour prior to sessions 4-10, the child will take either 1 or 2 pills containing 25mg of placebo. The number of pills depends on the child's weight (e.g., about 46kgs takes 2 capsules).	Involves receiving cognitive-behavioral treatment of OCD symptoms for 10 sessions. One hour prior to sessions 4-10, the child will take either 1 or 2 pills containing 25mg of D-cycloserine. The number of pills depends on the child's weight (e.g., about 46kgs takes 2 capsules).
Period Title: Overall Study
Started	15	15
Completed	15	15
Not Completed	0	0

Baseline Characteristics

Arm/Group Title		Cognitive-behavioral Therapy + Placebo	Cognitive-behavioral Therapy + D-cycloserine	Total
Arm/Group Description		Involves receiving cognitive-behavioral treatment of OCD symptoms for 10 sessions. One hour prior to sessions 4-10, the child will take either 1 or 2 pills containing 25mg of placebo. The number of pills depends on the child's weight (e.g., about 46kgs takes 2 capsules).	Involves receiving cognitive-behavioral treatment of OCD symptoms for 10 sessions. One hour prior to sessions 4-10, the child will take either 1 or 2 pills containing 25mg of D-cycloserine. The number of pills depends on the child's weight (e.g., about 46kgs takes 2 capsules).	Total of all reporting groups
Overall Number of Baseline Participants		15	15	30
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants	15 participants	30 participants
	<=18 years	15 100.0%	15 100.0%	30 100.0%
	Between 18 and 65 years	0 0.0%	0 0.0%	0 0.0%
	>=65 years	0 0.0%	0 0.0%	0 0.0%
Age Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	15 participants	15 participants	30 participants
		12.5 (3.5)	11.9 (1.9)	12.2 (2.8)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	15 participants	15 participants	30 participants
	Female	6 40.0%	5 33.3%	11 36.7%
	Male	9 60.0%	10 66.7%	19 63.3%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	15 participants	15 participants	30 participants
		15	15	30

Outcome Measures

1. Primary Outcome

Title	Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS; Scahill et al., 1997).
Description	The CY-BOCS is a 10-item semi-structured measure of obsession and compulsion severity over the previous week. This measure served as the primary outcome index. Scores range from 0-40 with higher scores representing more severe symptoms.
Time Frame	Baseline, Mid-Treatment, Post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive-behavioral Therapy + Placebo	Cognitive-behavioral Therapy + D-cycloserine
Arm/Group Description:	Involves receiving cognitive-behavioral treatment of OCD symptoms for 10 sessions. One hour prior to sessions 4-10, the child will take either 1 or 2 pills containing 25mg of placebo. The number of pills depends on the child's weight (e.g., about 46kgs takes 2 capsules).	Involves receiving cognitive-behavioral treatment of OCD symptoms for 10 sessions. One hour prior to sessions 4-10, the child will take either 1 or 2 pills containing 25mg of D-cycloserine. The number of pills depends on the child's weight (e.g., about 46kgs takes 2 capsules).
Overall Number of Participants Analyzed	15	15
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	26 (3.8)	24.1 (4.4)
Mid-treatment	17.9 (4.5)	15.6 (6.8)
Post-treatment	11 (6.6)	6.8 (6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive-behavioral Therapy + Placebo, Cognitive-behavioral Therapy + D-cycloserine
	Comments	Data were analyzed with separate 2 (site: Florida, MGH) by 2 (condition: CBT+DCS, CBT+Placebo) by 3 (time: pre-treatment, mid-treatment, post-treatment; Dependent variables: CY-BOCS Total Score) fixed-effects linear regression with time as the repeated measure. Cohen's d was used to examine the magnitude of treatment effects.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	ANOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	11.0
	Parameter Dispersion	Type: Standard Deviation; Value: 6.3
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Clinical Global Impression - Severity (CGI-S; National Institute of Mental Health, 1985). The CGI-S is a 7-point Clinician Rating of Severity of Psychopathology.
Description	The CGI-S is a 7-point clinician rating of severity of psychopathology. Ratings range from 1 ("no illness") to 7 ("extremely severe"). A single rating is chosen for the CGI-S; thus, there are no summary scales/scores.
Time Frame	Baseline, mid-treatment, post-treatment

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Cognitive-behavioral Therapy + Placebo	Cognitive-behavioral Therapy + D-cycloserine
Arm/Group Description:	Involves receiving cognitive-behavioral treatment of OCD symptoms for 10 sessions. One hour prior to sessions 4-10, the child will take either 1 or 2 pills containing 25mg of placebo. The number of pills depends on the child's weight (e.g., about 46kgs takes 2 capsules).	Involves receiving cognitive-behavioral treatment of OCD symptoms for 10 sessions. One hour prior to sessions 4-10, the child will take either 1 or 2 pills containing 25mg of D-cycloserine. The number of pills depends on the child's weight (e.g., about 46kgs takes 2 capsules).
Overall Number of Participants Analyzed	15	15
Mean (Standard Deviation); Unit of Measure: units on a scale
Baseline	5.1 (.74)	4.6 (.83)
Mid-treatment	3.9 (.59)	3.5 (.92)
Post-treatment	3 (1.2)	2 (1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Cognitive-behavioral Therapy + Placebo, Cognitive-behavioral Therapy + D-cycloserine
	Comments	Data were analyzed with separate 2 (site: Florida, MGH) by 2 (condition: CBT+DCS, CBT+Placebo) by 3 (time: pre-treatment, mid-treatment, post-treatment; Dependent variables: CGI-Severity) fixed-effects linear regression with time as the repeated measure. Cohen's d was used to examine the magnitude of treatment effects.
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.05
	Comments	[Not Specified]
	Method	ANOVA
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	3
	Parameter Dispersion	Type: Standard Deviation; Value: 1.1
	Estimation Comments	[Not Specified]

3. Secondary Outcome

Title	Adverse Symptom Checklist (ASC; Goodman, 2005).
Description	This index assesses adverse side effects that have been associated with DCS, as well as other commonly used psychotropic agents (e.g., SRIs). There are no summary scales for this. Rather, it reflects the presence or absence of 30 potential side effects on a 0-3 scale (0=not at all, 1=slight, 2=moderate, 3=severe) that are associated with study interventions.
Time Frame	Baseline, mid-treatment, post-treatment

Outcome Measure Data

Analysis Population Description

Number of participants experiencing an adverse effect related to study interventions. This is a simple frequency count.

Arm/Group Title	Cognitive-behavioral Therapy + Placebo	Cognitive-behavioral Therapy + D-cycloserine
Arm/Group Description:	Involves receiving cognitive-behavioral treatment of OCD symptoms for 10 sessions. One hour prior to sessions 4-10, the child will take either 1 or 2 pills containing 25mg of placebo. The number of pills depends on the child's weight (e.g., about 46kgs takes 2 capsules).	Involves receiving cognitive-behavioral treatment of OCD symptoms for 10 sessions. One hour prior to sessions 4-10, the child will take either 1 or 2 pills containing 25mg of D-cycloserine. The number of pills depends on the child's weight (e.g., about 46kgs takes 2 capsules).
Overall Number of Participants Analyzed	15	15
Measure Type: Number; Unit of Measure: participants
Baseline	0	0
Mid-treatment	0	0
Post-treatment	0	0

Adverse Events

Time Frame	[Not Specified]
Adverse Event Reporting Description	This metric refers to the number of youth experiencing an adverse event associated with study interventions.
Arm/Group Title	Cognitive-behavioral Therapy + Placebo	Cognitive-behavioral Therapy + D-cycloserine
Arm/Group Description	Involves receiving cognitive-behavioral treatment of OCD symptoms for 10 sessions. One hour prior to sessions 4-10, the child will take either 1 or 2 pills containing 25mg of placebo. The number of pills depends on the child's weight (e.g., about 46kgs takes 2 capsules).	Involves receiving cognitive-behavioral treatment of OCD symptoms for 10 sessions. One hour prior to sessions 4-10, the child will take either 1 or 2 pills containing 25mg of D-cycloserine. The number of pills depends on the child's weight (e.g., about 46kgs takes 2 capsules).
All-Cause Mortality
	Cognitive-behavioral Therapy + Placebo	Cognitive-behavioral Therapy + D-cycloserine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--
Serious Adverse Events
	Cognitive-behavioral Therapy + Placebo	Cognitive-behavioral Therapy + D-cycloserine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/15 (0.00%)	0/15 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Cognitive-behavioral Therapy + Placebo	Cognitive-behavioral Therapy + D-cycloserine
	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/15 (0.00%)	0/15 (0.00%)

Limitations and 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.

Results Point of Contact

• Name/Title: Eric Storch, Ph.D.
• Organization: University of South Florida
• Phone: 727-767-8230
• EMail: estorch@health.usf.edu

Publications of Results:

Storch EA, Murphy TK, Goodman WK, Geffken GR, Lewin AB, Henin A, Micco JA, Sprich S, Wilhelm S, Bengtson M, Geller DA. A preliminary study of D-cycloserine augmentation of cognitive-behavioral therapy in pediatric obsessive-compulsive disorder. Biol Psychiatry. 2010 Dec 1;68(11):1073-6. doi: 10.1016/j.biopsych.2010.07.015.

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

Guzick AG, Geller DA, Small BJ, Murphy TK, Wilhelm S, Storch EA. Irritability in Children and Adolescents With OCD. Behav Ther. 2021 Jul;52(4):883-896. doi: 10.1016/j.beth.2020.11.001. Epub 2020 Nov 12.

Storch EA, McGuire JF, Schneider SC, Small BJ, Murphy TK, Wilhelm S, Geller DA. Sudden gains in cognitive behavioral therapy among children and adolescents with obsessive compulsive disorder. J Behav Ther Exp Psychiatry. 2019 Sep;64:92-98. doi: 10.1016/j.jbtep.2019.03.003. Epub 2019 Mar 9.

Wilhelm S, Berman N, Small BJ, Porth R, Storch EA, Geller D. D-Cycloserine augmentation of cognitive behavior therapy for pediatric OCD: Predictors and moderators of outcome. J Affect Disord. 2018 Dec 1;241:454-460. doi: 10.1016/j.jad.2018.07.042. Epub 2018 Jul 20.

Storch EA, Wilhelm S, Sprich S, Henin A, Micco J, Small BJ, McGuire J, Mutch PJ, Lewin AB, Murphy TK, Geller DA. Efficacy of Augmentation of Cognitive Behavior Therapy With Weight-Adjusted d-Cycloserine vs Placebo in Pediatric Obsessive-Compulsive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2016 Aug 1;73(8):779-88. doi: 10.1001/jamapsychiatry.2016.1128.

• Responsible Party: Eric Storch, University of South Florida
• ClinicalTrials.gov Identifier: NCT00864123
• Other Study ID Numbers: MH076775; MH076775
• First Submitted: March 17, 2009
• First Posted: March 18, 2009
• Results First Submitted: June 26, 2012
• Results First Posted: October 17, 2012
• Last Update Posted: October 17, 2012