Obsessive-Compulsive Disorder
Conditions
Brief summary
The purpose of this study is to find out if D-Cycloserine (DCS), taken at the same time as a child gets cognitive behavioral therapy (CBT) can help children with pediatric obsessive-compulsive disorder. Cognitive Behavior Therapy is a talking therapy that will teach children new skills to better cope with his/her OCD. CBT usually uses exposure-based therapy. This means that the person with OCD slowly learns to deal with things they usually avoid. This is done by moving from less stressful situations to more challenging ones. The investigators hope to enroll about 75 children ages 7-17 years old with OCD in this study at Massachusetts General Hospital (MGH). The National Institute of Mental Health (NIMH) is paying for this study to be done. If your child qualifies for the study, the investigators will assign him or her by chance (like a coin toss) to either the DCS group or the placebo group. You and the study doctor cannot choose your child's study group. Your child will have an equal chance (1 in 2) of being assigned to the DCS group. Your child will be asked to take one or two capsules of the study drug (either DCS or placebo, depending which study group they were assigned to) one hour before CBT visits 4-10. The study coordinator will give your child the study drug at the location of the CBT sessions. This is to make sure that your child takes the study drug one hour before his/her scheduled therapy session. We will ask you to record any bad side effect from the study drug that your child may have before each CBT session. It will take your child about 34 weeks to complete the study. During this time, the investigators will ask you and your child to make a minimum of 17 trips to the study center. There may be up to 23 trips when including CBT Booster sessions. This study uses a placebo. The placebo looks exactly like the DCS, but it contains no DCS. The investigators use placebos in research studies to learn if the the results are caused by the study drug or are due to other reasons. This is a double-blind study. A double-blind study is a study where both the doctor and the study participant do not know whether the study participant is being given DCS or placebo.
Interventions
DRUGD-Cycloserine
25mg dose for children weighing between 22.5kg and 45kg (dose = approx. .7mg/kg) 50mg dose for children weighing greater than 46kg (dose = approx. .7mg/kg) Dose given 7 times, every seven days, except for the third dose, which will be given three days after the second dose. All doses given 1 hour prior to therapy session.
DRUGPlacebo
Sugar pill
Sponsors
National Institute of Mental Health (NIMH)
University of South Florida
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
7 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Clinical diagnosis of Obsessive-Compulsive Disorder as primary or co-primary diagnosis * Score on CY-BOCS of 16 or greater * Full Scale IQ greater than or equal to 85 * English speaking
Exclusion criteria
* Receiving concurrent psychotherapy or a past adequate trial of CBT for OCD * Initiation of an antidepressant within 12 weeks before study enrollment * Initiation of an antipsychotic within 6 weeks before study enrollment * No new alternative medications, nutritionals, or therapeutic diets within 6 weeks of study enrollment * Any change in established psychotropic medication within 8 weeks before study enrollment (6 weeks for antipsychotic). Alternative medications must be stable for 6 weeks prior to baseline. Any medications must remain stable during treatment. * Current clinically significant suicidality * Suicidal behaviors within six months * DSM-IV conduct disorder * DSM-IV autism * DSM-IV bipolar * DSM-IV schizophrenia or schizo-affective disorders * Substance abuse within the past six months * Hoarding symptoms (due to difficulty implementing E/RP tasks) * Weight less than 22.5k * Epilepsy or renal insufficiency * Current and/or past history of alcohol abuse (DCS is contraindicated) * Pregnant or having unprotected sex (in females) * Presence of a significant and/or unstable medical illness that might lead to hospitalization during the study * Known DCS allergy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) | Change from Score at Randomization to Post Treatment | The CY-BOCS is a measure of severity of OCD symptoms, including interference, time spent on thoughts or behaviors, distress, resistance, etc. The CY-BOCS is measured from 0 to 40, with larger values indicating more severe symptoms. Our outcome measure was the difference between the post treatment and randomization scores. When those values are negative, it indicates a reduction in symptom severity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Global Impression-Severity (CGI-Severity) | Change from Randomization Point to Post Treatment | The Clinical Global Impression-Severity is a 7-point clinician rating of illness severity, with a score of 0 indicating no illness and a score of 6 indicating extremely severe symptoms. Because the secondary outcome was the change in score from randomization to post treatment, a more negative score indicates a greater reduction in symptom severity. |
Countries
United States
Participant flow
Pre-assignment details
206 subjects were initially enrolled at MGH and USF. Of those, 32 were considered screen fails and 32 were not randomized either because they did not meet inclusion or exclusion criteria at randomization or because they withdrew consent or dropped out. Thus, 142 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| D-Cycloserine D-Cycloserine: 25mg dose for children weighing between 22.5kg and 45kg (dose = approx. .7mg/kg) 50mg dose for children weighing greater than 46kg (dose = approx. .7mg/kg) Dose given 7 times, every seven days, except for the third dose, which will be given three days after the second dose. All doses given 1 hour prior to therapy session. | 70 |
| Sugar Pill Placebo: Sugar pill | 72 |
| Total | 142 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Discontinued | 3 | 0 |
Baseline characteristics
| Characteristic | Sugar Pill | Total | D-Cycloserine |
|---|---|---|---|
| Age, Continuous | 12.14 Years STANDARD_DEVIATION 2.97 | 12.40 Years STANDARD_DEVIATION 2.95 | 12.67 Years STANDARD_DEVIATION 2.94 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 10 Participants | 22 Participants | 12 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 62 Participants | 120 Participants | 58 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 5 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 8 Participants | 4 Participants |
| Race (NIH/OMB) White | 65 Participants | 126 Participants | 61 Participants |
| Sex: Female, Male Female | 34 Participants | 76 Participants | 42 Participants |
| Sex: Female, Male Male | 38 Participants | 66 Participants | 28 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 60 / 70 | 70 / 72 |
| serious Total, serious adverse events | 0 / 70 | 0 / 72 |
Outcome results
Primary
Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS)
The CY-BOCS is a measure of severity of OCD symptoms, including interference, time spent on thoughts or behaviors, distress, resistance, etc. The CY-BOCS is measured from 0 to 40, with larger values indicating more severe symptoms. Our outcome measure was the difference between the post treatment and randomization scores. When those values are negative, it indicates a reduction in symptom severity.
Time frame: Change from Score at Randomization to Post Treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-Cycloserine | Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) | -10.35 Change in score from randomization | Standard Deviation 7.72 |
| Sugar Pill | Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS) | -9.40 Change in score from randomization | Standard Deviation 7.05 |
Secondary
Clinical Global Impression-Severity (CGI-Severity)
The Clinical Global Impression-Severity is a 7-point clinician rating of illness severity, with a score of 0 indicating no illness and a score of 6 indicating extremely severe symptoms. Because the secondary outcome was the change in score from randomization to post treatment, a more negative score indicates a greater reduction in symptom severity.
Time frame: Change from Randomization Point to Post Treatment
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| D-Cycloserine | Clinical Global Impression-Severity (CGI-Severity) | -1.39 Change in score from randomization | Standard Deviation 1.04 |
| Sugar Pill | Clinical Global Impression-Severity (CGI-Severity) | -1.2 Change in score from randomization | Standard Deviation 0.91 |