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

Obsessive-compulsive Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00864123
• Other study ID #: MH076775
• Secondary ID: MH076775
• Status: Completed
• Phase: Phase 2
• First received: March 17, 2009
• Last updated: September 14, 2012
• Start date: January 2008
• Est. completion date: November 2009

Study information

• Verified date: September 2012
• Source: University of South Florida
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: November 2009
• Est. primary completion date: November 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 8 Years to 17 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Compulsive Behavior
• Obsessive-Compulsive Disorder

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	University of South Florida	St. Petersburg	Florida

Sponsors (1)

Lead Sponsor	Collaborator
University of South Florida

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 Psych — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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 served as the primary outcome index. Scores range from 0-40 with higher scores representing more severe symptoms.	Baseline, Mid-Treatment, Post-treatment	No
Secondary	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.	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.	Baseline, mid-treatment, post-treatment	No
Secondary	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). 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.	Baseline, mid-treatment, post-treatment	Yes