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

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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:
Information provided by (Responsible Party):
Eric Storch, University of South Florida

Tracking Information
First Submitted Date  ICMJE March 17, 2009
First Posted Date  ICMJE March 18, 2009
Results First Submitted Date  ICMJE June 26, 2012
Results First Posted Date  ICMJE October 17, 2012
Last Update Posted Date October 17, 2012
Study Start Date  ICMJE January 2008
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 14, 2012)
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 Measures  ICMJE
 (submitted: March 17, 2009)
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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: September 14, 2012)
  • 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 Measures  ICMJE
 (submitted: March 17, 2009)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE D-Cycloserine Augmentation of Therapy for Pediatric Obsessive-Compulsive Disorder
Official Title  ICMJE 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 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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Obsessive-compulsive Disorder
Intervention  ICMJE
  • Behavioral: Cognitive-behavioral therapy
    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).
  • Drug: D-cycloserine
    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.
    Other Names:
    • Seromycin
    • d-4-amino-3-isoxazolidone
  • Drug: Placebo pill
    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 Name: Pill placebo
Study Arms  ICMJE
  • Active Comparator: Cognitive-behavioral therapy + placebo
    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).
    Interventions:
    • Behavioral: Cognitive-behavioral therapy
    • Drug: Placebo pill
  • Experimental: Cognitive-behavioral therapy + D-cycloserine
    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).
    Interventions:
    • Behavioral: Cognitive-behavioral therapy
    • Drug: D-cycloserine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: September 14, 2012)
30
Original Estimated Enrollment  ICMJE
 (submitted: March 17, 2009)
40
Actual Study Completion Date  ICMJE November 2009
Actual Primary Completion Date November 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • The child must receive a principal diagnosis of OCD at Baseline, based on DSM-IV criteria. This diagnosis will be derived from the Anxiety Disorder Interview Schedule for DSM-IV-Child Interview Schedule - Parent version (ADIS-IV-P), and must reflect a clinical severity rating of 4 or above
  • CY-BOCS Total Score ≥ 16
  • Be between the ages of 8 and 17 years
  • Score ≥ 80 on the Peabody Picture Vocabulary Test-3rd Edition (Dunn & Dunn, 1997)
  • At least one parent available to accompany the child to all sessions;
  • English speaking.

Exclusion Criteria:

  • Psychosis, pervasive developmental disorder, bipolar disorder, or current suicidal intent measured by the ADIS-IV-P and all available clinical information
  • Principal diagnosis other than OCD
  • Youth with mental rituals, incompleteness, or hoarding symptoms as E/RP exercises would be more difficult to conduct/monitor than those with overt rituals
  • Unavailability of at least one caregiver to participate in the treatment
  • Refusal of parent to accept random assignment to treatment condition
  • A positive diagnosis in the caregiver of mental retardation, psychosis, clinically significant tics, or other psychiatric disorders or conditions that would limit their ability to understand E/RP (based on clinical interview)
  • Weight less than 25.0 kg or greater than 80.0kg
  • Epilepsy, renal insufficiency, and current or past history of alcohol abuse (DCS is contraindicated for such conditions)
  • Pregnant or having unprotected sex [in females] as the effects of DCS on pregnant youth are unknown
  • General poor physical health as determined by medical physical and laboratory tests.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 8 Years to 17 Years   (Child)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00864123
Other Study ID Numbers  ICMJE MH076775
MH076775
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party Eric Storch, University of South Florida
Original Responsible Party Eric Storch, University of South Florida
Current Study Sponsor  ICMJE University of South Florida
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Eric Storch, Ph.D. University of South Florida
PRS Account University of South Florida
Verification Date September 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP