D-Cycloserine Augmentation of Therapy for Pediatric Obsessive-Compulsive Disorder
Condition: Obsessive-compulsive Disorder
MeSH terms: Compulsive Personality Disorder; Obsessive-Compulsive Disorder
Study type: Interventional
Phase: Phase 2

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 description: 
      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), whereas one midpoint assessment will
      involve administration of CY-BOCS, CGI, CGI-S, and Adverse Symptom Checklist only. Results
      from this study may have powerful clinical implications by providing preliminary support for
      pharmalogical agents that enhance the effectiveness of standard E/RP. Such agents may have
      utility in improving outcome, reducing premature therapy termination, and targeting patients
      who have been treatment refractory.
    

Intervention name(s): Cognitive-behavioral therapy; D-cycloserine; Placebo pill
Intervention type(s): Behavioral; Drug; Drug
Intervention description(s): All patients will receive 10 sessions of therapy over 8 weeks that is based on the protocol used in POTS (2004). Sessions 1-4 will be held twice weekly; thereafter sessions will be held on a weekly basis. This evidence-based E/RP intervention (POTS, 2004) includes psychoeducation, cognitive training, and exposure and response prevention. By design, this manual provides sufficient flexibility to accommodate the child's developmental needs and address maladaptive parent-child interactions (e.g., accommodation).; D-cycloserine (Seromycin, 250 mg; Eli Lilly and Co, Indianapolis, Indiana) will be capsulated into 25mg with identical placebo capsules. Children weighing between 25-45kg will be given a dosage of 25mg (approximately 0.56-1.0 mg/kg/day). Children weighing between 46-80kg will be given a dosage of 50mg (approximately 0.63-1.08mg/kg/day). DCS or placebo will be given by parents 1 hour prior to psychotherapy sessions (before sessions 4-10 only) based on past success in patients with acrophobia (Ressler et al., 2004) and DCS absorption rates.; This intervention involves taking a placebo pill(s) that matches the d-cycloserine capsules in size, shape, weight, and taste. Placebo contains an no active medication.
Other intervention name(s): Seromycin; d-4-amino-3-isoxazolidone; Pill placebo
Intervention MeSH terms: Cycloserine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Obsessive-compulsive disorder