Obsessive Compulsive Disorder
Conditions
Keywords
OCD, DCS, D-cycloserine, CBT, E/RP, exposure response prevention
Brief summary
This is a single site, open-label, feasibility study of cognitive behavioral therapy with exposure and response prevention (CBT/ERP) adding the augmentation of D-cycloserine (DCS) for adolescents ages 12-17 with Obsessive Compulsive Disorder (OCD) who are partial or non-responders to first line treatments of CBT or pharmacotherapy.
Detailed description
The primary goal of this study is to examine the feasibility and efficacy of DCS augmentation to CBT/ERP at the end of the session. The main treatment outcome will be measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The secondary goal of the study is to investigate the safety of DCS in adolescents with OCD. 18 adolescents will be recruited in this study. Patients who are currently on medication therapies for OCD must be stable for at least 12 weeks prior to and during the study. This study consists of a screening period that contains a 90-minute psycho-educational session and treatment period of up to 5 weeks. During the treatment period, patients will receive ten 60-minute CBT/ERP sessions held twice weekly. At the end of each session, patients will receive a 50 mg dose of DCS. Following the administration of the DCS, patients will be asked to do their best not to ritualize and remain on the Children's Day Unit, where they will be observed and report to the research team if any ritualization has occurred. At the end of study participation, all participants will be offered 10 additional sessions of twice-weekly ERP without DCS administration. All participants will then complete a follow-up visit at 10 weeks after baseline. The main treatment outcome will be measured by the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). The secondary goal of the study is to investigate the safety of DCS in adolescents with OCD. Additionally, we will explore the impact of patient's motivation to change, parental pathology, and family accommodation on the treatment progress and outcome in adolescents. Present data collected from this protocol show that adolescents who completed and engaged in treatment experienced benefit to the combination of CBT/ERP and DCS. However, this is an unblinded study and the adolescents are receiving an intensive form of CBT/ERP with close monitoring following 2 hours after the administration of the DCS. The positive results may be due to this specific way in which the CBT/ERP was delivered or to the attention paid to participants during treatment sessions and monitoring periods. We recruited 5 additional adolescents diagnosed with OCD to serve as control group participants. These individuals all had a history of failed or partial response to at least one trial of Selective Serotonin Reuptake Inhibitor (SSRI) medication or CBT/ERP. These participants also received ten sessions of twice weekly CBT/ERP delivered exactly as it was previously in this protocol, but without DCS administration. All control participants completed a follow-up visit at 10 weeks after baseline. Due to the small number of control participants, statistical analyses comparing the treatment groups were not completed.
Interventions
DRUGD-cycloserine
50 mg dose of D-cycloserine administered at the end of each session of Cognitive Behavioral Therapy With Exposure and Response Prevention: twice weekly CBT/ERP of 60 minutes
BEHAVIORALExposure and Response Prevention (EX/RP)
Exposure and response prevention treatment. Participants complete graded exposure during twice weekly treatment sessions with therapist
Sponsors
Emory University
New York State Psychiatric Institute
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
Inclusion/
Exclusion criteria
Inclusion Criteria: 1. Patients must be ages of 12-17 at the time of consent. 2. Both patients and parents must be able to speak and understand English. 3. Written informed assent by the patient and consent by the parent. 4. Ability and willingness to comply with study treatment and to attend study assessments. 5. Patients must be physically healthy males or non-pregnant females. Females of childbearing potential must comply with contraceptive restrictions noted in the protocol. 6. Patients must fulfill Diagnostic and Statistical Manual (DSM-IV) criteria for OCD, and OCD must be the primary disorder with a CY-BOCS score \> 16 7. For patients with attention-deficit hyperactivity disorder (ADHD), the condition must be stable for 4 weeks on present treatment prior to screening. 8. For patients receiving treatment with an FDA approved Serotonin Reuptake Inhibitor (SRI), the medication dose must be stable for at least 12 weeks prior to enrollment. 9. Patients who failed to respond to either CBT/ERP treatment or a SRI medication (as evidenced by a CY-BOCS score \> 16). 10. Based on history, the patient is unlikely to require a change in medication during the course of CBT/ERP + DCS treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS) for Adolescents | baseline, visit 5, visit 10, follow-up visit | The CYBOCS is a semi-structured measure of Obsessive Compulsive Disorder (OCD) severity with excellent inter-rater reliability, internal consistency, and test-retest reliability. It is validated in those starting at age 7 and used in studies up to age 20.The CYBOCS differs from the adult Yale-Brown Obsessive Compulsive Scale (YBOCS) only in its use of simpler language. CYBOCS scores range from 0-40, with higher scores representing greater severity of symptoms. The CYBOCS will be administered by independent evaluators (IEs) at baseline, session 5, session 10 and the follow-up visit. It will be the primary outcome measure. The CYBOCS checklist will be used to determine symptom dimensions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Multidimensional Anxiety Scale for Children (MASC) | baseline, visit 5, visit 10, follow-up visit | Multidimensional Anxiety Scale for Children (MASC): This is a 39-item self-report that measures anxiety symptoms. It provides a total score, as well as 10 subscales, although only total scores will be analyzed. MASC scores range from 0-117, with higher scores representing greater severity of anxiety symptoms. The MASC and will be administered at baseline, session 5, session 10 and the follow-up visit for adolescents. |
| Beck Depression Inventory (BDI) | baseline, visit 5, visit 10, follow-up visit | Beck's Depression Inventory (BDI): This is a 21-item self report that measures depression symptoms and will be used for both adults and adolescents at baseline, session 5, session 10 and the follow-up visit. BDI-II scores range from 0-63, with higher scores representing greater severity of depression symptoms. |
Countries
United States
Participant flow
Recruitment details
Recruitment was drawn from the broadest possible population with respect to gender and ethnic origin. Internal Review Board(IRB)-approved web/radio/newspaper ads & flyers were used to recruit patients, as were physician and mental health practitioner referrals.
Pre-assignment details
16 adolescents(12-17yrs) participated in the study. The initial 11 participants received 10 twice-weekly sessions of exposure and response prevention treatment (E/RP) as well as D-Cycloserine(DCS) 50mg at each session. The final 5 participants received 10 twice-weekly sessions of E/RP treatment alone during the active study period.
Participants by arm
| Arm | Count |
|---|---|
| D-cycloserine + E/RP Participants in this treatment arm received 10 twice-weekly sessions of E/RP treatment and were administered D-Cycloserine (DCS) immediately after every treatment visit. | 11 |
| E/RP Alone (no DCS Administration) Five participants were enrolled in the second treatment arm as a comparison. The participants received 10 twice-weekly sessions of E/RP treatment alone. | 5 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | E/RP Alone (no DCS Administration) | D-cycloserine + E/RP | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 5 Participants | 11 Participants | 16 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Continuous | 16.25 years STANDARD_DEVIATION 0.96 | 15.67 years STANDARD_DEVIATION 1.32 | 15.85 years STANDARD_DEVIATION 1.21 |
| Region of Enrollment United States | 5 participants | 11 participants | 16 participants |
| Sex: Female, Male Female | 2 Participants | 5 Participants | 7 Participants |
| Sex: Female, Male Male | 3 Participants | 6 Participants | 9 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 6 / 11 | 2 / 5 |
| serious Total, serious adverse events | 1 / 11 | 1 / 5 |
Outcome results
Primary
Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS) for Adolescents
The CYBOCS is a semi-structured measure of Obsessive Compulsive Disorder (OCD) severity with excellent inter-rater reliability, internal consistency, and test-retest reliability. It is validated in those starting at age 7 and used in studies up to age 20.The CYBOCS differs from the adult Yale-Brown Obsessive Compulsive Scale (YBOCS) only in its use of simpler language. CYBOCS scores range from 0-40, with higher scores representing greater severity of symptoms. The CYBOCS will be administered by independent evaluators (IEs) at baseline, session 5, session 10 and the follow-up visit. It will be the primary outcome measure. The CYBOCS checklist will be used to determine symptom dimensions.
Time frame: baseline, visit 5, visit 10, follow-up visit
Population: Data from 14 adolescents were analyzed. One participant was excluded from analyses because he did not receive DCS at every treatment visit. Another was excluded because she was unable to provide reliable data on outcome measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D-cycloserine + E/RP | Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS) for Adolescents | Session 10 CYBOCS | 19.67 units on a scale | Standard Deviation 8.77 |
| D-cycloserine + E/RP | Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS) for Adolescents | Baseline CYBOCS | 26.56 units on a scale | Standard Deviation 3.91 |
| D-cycloserine + E/RP | Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS) for Adolescents | Follow-Up CYBOCS | 14.5 units on a scale | Standard Deviation 7.78 |
| D-cycloserine + E/RP | Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS) for Adolescents | Session 5 CYBOCS | 22.44 units on a scale | Standard Deviation 5.17 |
| E/RP Alone (no DCS Administration) | Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS) for Adolescents | Follow-Up CYBOCS | 22 units on a scale | Standard Deviation 3.61 |
| E/RP Alone (no DCS Administration) | Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS) for Adolescents | Session 5 CYBOCS | 19.8 units on a scale | Standard Deviation 7.26 |
| E/RP Alone (no DCS Administration) | Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS) for Adolescents | Session 10 CYBOCS | 17.2 units on a scale | Standard Deviation 11.55 |
| E/RP Alone (no DCS Administration) | Child Yale-Brown Obsessive Compulsive Scale (CY-BOCS) for Adolescents | Baseline CYBOCS | 27.25 units on a scale | Standard Deviation 3.6 |
Secondary
Beck Depression Inventory (BDI)
Beck's Depression Inventory (BDI): This is a 21-item self report that measures depression symptoms and will be used for both adults and adolescents at baseline, session 5, session 10 and the follow-up visit. BDI-II scores range from 0-63, with higher scores representing greater severity of depression symptoms.
Time frame: baseline, visit 5, visit 10, follow-up visit
Population: Data from 14 adolescents were analyzed. One participant was excluded from analyses because he did not receive DCS at every treatment visit. Another was excluded because she was unable to provide reliable data on outcome measures. Another was excluded because she was unable to provide reliable data on outcome measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D-cycloserine + E/RP | Beck Depression Inventory (BDI) | Baseline BDI | 13.11 units on a scale | Standard Deviation 12.41 |
| D-cycloserine + E/RP | Beck Depression Inventory (BDI) | Session 10 BDI | 9.67 units on a scale | Standard Deviation 7.21 |
| D-cycloserine + E/RP | Beck Depression Inventory (BDI) | Follow-Up BDI | NA units on a scale | — |
| D-cycloserine + E/RP | Beck Depression Inventory (BDI) | Session 5 BDI | 11.33 units on a scale | Standard Deviation 8.23 |
| E/RP Alone (no DCS Administration) | Beck Depression Inventory (BDI) | Session 5 BDI | 4.8 units on a scale | Standard Deviation 2.95 |
| E/RP Alone (no DCS Administration) | Beck Depression Inventory (BDI) | Baseline BDI | 12.5 units on a scale | Standard Deviation 0.71 |
| E/RP Alone (no DCS Administration) | Beck Depression Inventory (BDI) | Follow-Up BDI | 4.34 units on a scale | Standard Deviation 1.53 |
| E/RP Alone (no DCS Administration) | Beck Depression Inventory (BDI) | Session 10 BDI | 4 units on a scale | Standard Deviation 2.35 |
Secondary
Multidimensional Anxiety Scale for Children (MASC)
Multidimensional Anxiety Scale for Children (MASC): This is a 39-item self-report that measures anxiety symptoms. It provides a total score, as well as 10 subscales, although only total scores will be analyzed. MASC scores range from 0-117, with higher scores representing greater severity of anxiety symptoms. The MASC and will be administered at baseline, session 5, session 10 and the follow-up visit for adolescents.
Time frame: baseline, visit 5, visit 10, follow-up visit
Population: Data from 14 adolescents were analyzed. One participant was excluded from analyses because he did not receive DCS at every treatment visit. Another was excluded because she was unable to provide reliable data on outcome measures.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| D-cycloserine + E/RP | Multidimensional Anxiety Scale for Children (MASC) | Follow-Up MASC | NA units on a scale | — |
| D-cycloserine + E/RP | Multidimensional Anxiety Scale for Children (MASC) | Session 10 MASC | 39.33 units on a scale | Standard Deviation 21.42 |
| D-cycloserine + E/RP | Multidimensional Anxiety Scale for Children (MASC) | Baseline MASC | 42.67 units on a scale | Standard Deviation 23.37 |
| D-cycloserine + E/RP | Multidimensional Anxiety Scale for Children (MASC) | Session 5 MASC | 40.56 units on a scale | Standard Deviation 19.79 |
| E/RP Alone (no DCS Administration) | Multidimensional Anxiety Scale for Children (MASC) | Session 10 MASC | 46.8 units on a scale | Standard Deviation 31.25 |
| E/RP Alone (no DCS Administration) | Multidimensional Anxiety Scale for Children (MASC) | Session 5 MASC | 47.4 units on a scale | Standard Deviation 29.72 |
| E/RP Alone (no DCS Administration) | Multidimensional Anxiety Scale for Children (MASC) | Baseline MASC | 52.4 units on a scale | Standard Deviation 23.56 |
| E/RP Alone (no DCS Administration) | Multidimensional Anxiety Scale for Children (MASC) | Follow-Up MASC | 40.5 units on a scale | Standard Deviation 41.72 |