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| ID | Type | Description | Link |
|---|---|---|---|
| MH076775 |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cognitive-behavioral therapy + placebo | Active Comparator | 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). |
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| Cognitive-behavioral therapy + D-cycloserine | Experimental | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cognitive-behavioral therapy | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| 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. | 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Eric Storch, Ph.D. | University of South Florida | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of South Florida | St. Petersburg | Florida | 33701 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 20817153 | Result | 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. | |
| 34134828 |
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Excluded (n = 22) Not interested in participating in study (n=9) Changing medication at Baseline (n=5) Did not receive at least one DCS dose (n = 4) History of adequate CBT course (n=2) Met criteria for comorbid autism (n=1) Did not show up for pre-treatment assessment (n=1)
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). |
| FG001 | 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). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline, Mid-Treatment, Post-treatment |
|
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This metric refers to the number of youth experiencing an adverse event associated with study interventions.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Eric Storch, Ph.D. | University of South Florida | 727-767-8230 | estorch@health.usf.edu |
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| ID | Term |
|---|---|
| D009771 | Obsessive-Compulsive Disorder |
| ID | Term |
|---|---|
| D001008 | Anxiety Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D015928 | Cognitive Behavioral Therapy |
| D003523 | Cycloserine |
| ID | Term |
|---|---|
| D001521 | Behavior Therapy |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |
| D007555 | Isoxazoles |
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| D-cycloserine | 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. |
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| Placebo pill | 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. |
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| 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 |
| 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. |
| 30877851 | Derived | 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. |
| 30149332 | Derived | 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. |
| 27367832 | Derived | 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. |
| 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). |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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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). |
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| 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. | Posted | Mean | Standard Deviation | units on a scale | Baseline, mid-treatment, post-treatment |
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| 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. | Number of participants experiencing an adverse effect related to study interventions. This is a simple frequency count. | Posted | Number | participants | Baseline, mid-treatment, post-treatment |
|
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| 0 |
| 15 |
| 0 |
| 15 |
| EG001 | 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). | 0 | 15 | 0 | 15 |
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| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
| D023303 | Oxazolidinones |
| D010080 | Oxazoles |
| D012694 | Serine |
| D021542 | Amino Acids, Neutral |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| Post-treatment |
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| Post-treatment |
|