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

September 14, 2012 updated by: Eric Storch, University of South Florida
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Florida
      • St. Petersburg, Florida, United States, 33701
        • University of South Florida

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

8 years to 17 years (CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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).
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: 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 Names:
  • Pill placebo
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).
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, Mid-Treatment, Post-treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Baseline, mid-treatment, post-treatment
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.
Baseline, mid-treatment, post-treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of South Florida

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2008

Primary Completion (ACTUAL)

November 1, 2009

Study Completion (ACTUAL)

November 1, 2009

Study Registration Dates

First Submitted

March 17, 2009

First Submitted That Met QC Criteria

March 17, 2009

First Posted (ESTIMATE)

March 18, 2009

Study Record Updates

Last Update Posted (ESTIMATE)

October 17, 2012

Last Update Submitted That Met QC Criteria

September 14, 2012

Last Verified

September 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MH076775

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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