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

NCT ID: NCT00864123

Last Updated: 2012-10-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2009-11-30

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.

Conditions

Obsessive-compulsive Disorder

Keywords

Obsessive-compulsive disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: ACTIVE_COMPARATOR

Cognitive-behavioral therapy

Intervention Type: BEHAVIORAL

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).

Placebo pill

Intervention Type: DRUG

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.

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).

Group Type: EXPERIMENTAL

Cognitive-behavioral therapy

Intervention Type: BEHAVIORAL

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

Intervention Type: DRUG

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.

Interventions

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).

Intervention Type: BEHAVIORAL

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Seromycin; d-4-amino-3-isoxazolidone; Pill placebo

Eligibility Criteria

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.

• Minimum Eligible Age: 8 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of South Florida

OTHER

Sponsor Role: lead

Responsible Party

Eric Storch

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Eric Storch, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of South Florida

Locations

University of South Florida

St. Petersburg, Florida, United States

Countries

United States

References

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 Psychiatry. 2010 Dec 1;68(11):1073-6. doi: 10.1016/j.biopsych.2010.07.015.

Reference Type: RESULT

PMID: 20817153 (View on PubMed)

Guzick AG, Geller DA, Small BJ, Murphy TK, Wilhelm S, Storch EA. Irritability in Children and Adolescents With OCD. Behav Ther. 2021 Jul;52(4):883-896. doi: 10.1016/j.beth.2020.11.001. Epub 2020 Nov 12.

Reference Type: DERIVED

PMID: 34134828 (View on PubMed)

Storch EA, McGuire JF, Schneider SC, Small BJ, Murphy TK, Wilhelm S, Geller DA. Sudden gains in cognitive behavioral therapy among children and adolescents with obsessive compulsive disorder. J Behav Ther Exp Psychiatry. 2019 Sep;64:92-98. doi: 10.1016/j.jbtep.2019.03.003. Epub 2019 Mar 9.

Reference Type: DERIVED

PMID: 30877851 (View on PubMed)

Wilhelm S, Berman N, Small BJ, Porth R, Storch EA, Geller D. D-Cycloserine augmentation of cognitive behavior therapy for pediatric OCD: Predictors and moderators of outcome. J Affect Disord. 2018 Dec 1;241:454-460. doi: 10.1016/j.jad.2018.07.042. Epub 2018 Jul 20.

Reference Type: DERIVED

PMID: 30149332 (View on PubMed)

Storch EA, Wilhelm S, Sprich S, Henin A, Micco J, Small BJ, McGuire J, Mutch PJ, Lewin AB, Murphy TK, Geller DA. Efficacy of Augmentation of Cognitive Behavior Therapy With Weight-Adjusted d-Cycloserine vs Placebo in Pediatric Obsessive-Compulsive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2016 Aug 1;73(8):779-88. doi: 10.1001/jamapsychiatry.2016.1128.

Reference Type: DERIVED

PMID: 27367832 (View on PubMed)

Other Identifiers

MH076775

Identifier Type: -

Identifier Source: secondary_id

MH076775

Identifier Type: -

Identifier Source: org_study_id