Clinical Trial: D-Cycloserine Augmentation of Therapy for Pediatric Obsessive-Compulsive Disorder

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: D-Cycloserine Augmentation of Therapy for Pediatric Obsessive-Compulsive Disorder

Brief Summary: Cognitive-behavioral therapy (CBT) has proven efficacy for treatment of pediatric obsessive-compulsive disorder (OCD). Yet, CBT does not help all children and those who benefit often remain symptomatic upon treatment completion. Recent clinical trials in adults with other anxiety disorders (acrophobia and social phobia) provided support for using a medication called D-Cycloserine (DCS) to enahnce the outcome of exposure-based psychotherapy. Given this, DCS may augment CBT in youth with OCD, an anxiety disorder that is conceptually similar to acrophobia. With this in mind, the investigators are conducting a randomized, double-blind placebo controlled pilot study of DCS to determine whether it had any short-term clinical benefits on CBT in youth with OCD. Forty children and adolescents (ages 8-17) with a primary diagnosis of OCD will be screened and, should they meet relevant criteria, randomly assigned to one of two treatment conditions: (1) CBT plus DCS, or (2) CBT plus placebo. All patients will receive 10 sessions of CBT A rater will assess participants at 3 separate time points.

Detailed Summary: Cognitive-behavioral therapy (CBT) has proven efficacy for treatment of pediatric obsessive-compulsive disorder (OCD). Yet, CBT does not help all children and those who benefit often remain symptomatic upon treatment completion. The behavioral theory that underlies CBT is based on two components, namely fear conditioning and extinction. On a neural level, CBT incorporates similar mechanisms to those involved in fear conditioning. Antagonists at the N-methyl-D-aspartate (NMDA) glutamatergic receptor, which is involved in learning and memory, block both fear learning and extinction. Evidence suggests that D-Cycloserine (DCS), a partial agonist at the NMDA glutamate receptor, augments associative learning and extinction as a form of learning in animals and humans. Recent clinical trials in adults with other anxiety disorders (acrophobia and social phobia) provided support for DCS dosing as facilitating associative learning that occurs during exposure-based psychotherapy. Given that CBT is based on the principles of extinction, DCS may augment CBT in youth with OCD, an anxiety disorder that is conceptually similar to acrophobia. With this in mind, I propose to undertake a randomized, double-blind placebo controlled pilot study of DCS to determine whether it had any short-term clinical benefits on CBT in youth with OCD. Forty children and adolescents (ages 8-17) with a primary diagnosis of OCD will be screened and, should they meet relevant criteria, randomly assigned to one of two treatment conditions: (1) CBT plus DCS (25 or 50mg depending on weight), or (2) CBT plus placebo. All patients will receive 10 sessions of CBT based on the protocol used in POTS (2004). Participants will take DCS or placebo 1 hour prior to each therapy session. A blinded, independent evaluator will assess participants at 3 separate time points. Two of the assessments (Baseline, Post-treatment) will be comprehensive in nature (e.g., diagnostic interview, self-reports, CY-BOCS, laboratory tests)
Sponsor: University of South Florida

Current Primary Outcome: Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS; Scahill et al., 1997). [ Time Frame: Baseline, Mid-Treatment, Post-treatment ]

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.


Original Primary Outcome: Children's Yale-Brown Obsessive-Compulsive Scale (CY-BOCS; Scahill et al., 1997). The CY-BOCS is a 10-item semi-structured measure of obsession and compulsion severity over the previous week. This measure will serve as the primary outcome index. [ Time Frame: Baseline, Mid-Treatment, Post-treatment ]

Current Secondary Outcome:

  • 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. [ Time Frame: Baseline, mid-treatment, post-treatment ]
    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.
  • Adverse Symptom Checklist (ASC; Goodman, 2005). [ Time Frame: Baseline, mid-treatment, post-treatment ]
    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.


Original Secondary Outcome:

  • 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. [ Time Frame: Baseline, mid-treatment, post-treatment ]
  • Adverse Symptom Checklist (ASC; Goodman, 2005). This index assesses adverse side effects that have been associated with DCS, as well as other commonly used psychotropic agents (e.g., SRIs). [ Time Frame: Baseline, mid-treatment, post-treatment ]


Information By: University of South Florida

Dates:
Date Received: March 17, 2009
Date Started: January 2008
Date Completion:
Last Updated: September 14, 2012
Last Verified: September 2012