Obsessive-compulsive DisorderPhase 3NCT01411774
D-cycloserine Augmentation of Cognitive Behavioral Therapy (CBT) for Pediatric Obsessive-compulsive Disorder (OCD)
A Phase 3 study testing Cognitive-behavioral therapy and d-cycloserine in people with Obsessive-compulsive Disorder, run by University of South Florida at 2 sites in United States.
Trial summary
The investigators are conducting a randomized double-blind placebo-controlled study to assess the efficacy of d-cycloserine augmentation of cognitive-behavioral therapy for the treatment of pediatric obsessive compulsive disorder. Read more about this study
- Who is it for?
- Ages 7 to 17 yearsHealthy volunteers can take part
- Conditions the study is for
- Obsessive-compulsive Disorder
- What is being tested?
- Cognitive-behavioral therapy and d-cycloserine
- Type of treatment
- Pill or oral medicine, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 142 participants
- Where
- 2 sitesUnited States
- Study dates
- Jun 2011to Jun 2017
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 7 to 17 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- Outpatient youth with obsessive-compulsive disorder between the ages 7-17 years.
- A Children's Yale-Brown Obsessive-Compulsive Scale score ≥ 16
- Child has a Full Scale IQ≥85 as assessed on the WASI (within 90% CI).
- English speaking
Who cannot join
- Receiving concurrent psychotherapy or a past adequate trial of CBT for OCD. Families will have the option of discontinuing such services to enroll in the study.
- New Treatments: Initiation of an antidepressant within 12 weeks before study enrollment or an antipsychotic 6 weeks before study enrollment. No new alternative medications, nutritionals or therapeutic diets within 6 weeks of study enrollment.
- Established Treatment changes: Any change in established psychotropic medication (e.g., antidepressants, anxioloytics, stimulant, alpha agonist) within 8 weeks before study enrollment (6 weeks for antipsychotic). Alternative medications must be stable for 6 weeks prior to baseline.
- Current clinically significant suicidality or individuals who have engaged in suicidal behaviors within 6 months will be excluded.
- DSM-IV conduct disorder, autism, bipolar, schizophrenia or schizoaffective disorders; or substance abuse in past 6 months using all available information.
- Youth with hoarding symptoms that are their primary form of OCD.
Show all 11Show fewer
- Weight less than 25.0 kg.
- Epilepsy, renal insufficiency, and current/past history of alcohol abuse.
- Pregnant or having unprotected sex [in females] as the effects of d-cycloserine on pregnancy are unknown.
- Presence of a significant and/or unstable medical illness that might lead to hospitalization during the study.
- Known d-cycloserine allergy.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Massachusetts General Hospital
Cambridge, Massachusetts, 02138
University of South Florida
St. Petersburg, Florida, 33701
About this study
Official title: 1/2 D-cycloserine Augmentation of CBT for Pediatric OCD
The investigators are conducting a randomized double-blind placebo-controlled study to assess the efficacy of d-cycloserine augmentation of cognitive-behavioral therapy for the treatment of pediatric obsessive compulsive disorder. This study represents an innovative approach in translating bench research findings into clinical research and testing a new approach for optimizing an effective psychotherapy with a safe non-psychotropic medication.
Read the detailed description
Obsessive-compulsive disorder (OCD) affects 1-2% of children, runs a chronic course without treatment, and is associated with considerable functional impairment and poor quality of life. Although most patients with OCD respond to cognitive-behavioral therapy (CBT) or pharmacotherapy with a serotonin reuptake inhibitor (SRI), a substantial number of youth remain symptomatic after receiving these therapies. Pharmacological interventions with SRIs are only moderately efficacious, rarely produce remission, may be accompanied by side effects, and may not be an acceptable intervention to some parents. Medication augmentation strategies such as atypical antipsychotics are often used in children with partial response but have concerning metabolic effects and no systematic supporting efficacy or safety data. Although CBT is the gold standard treatment for pediatric OCD, not all patients benefit and the availability of skilled therapists is quite limited. Thus, there is a critical need for interventions to optimize treatment outcome in pediatric OCD. The primary mechanism in CBT is repeated and prolonged exposure to feared situations while abstaining from OCD rituals. This treatment is based on animal models of extinction of conditioned fears. Basic research on the neural circuitry underlying fear extinction led to the examination of d-cycloserine (DCS), a partial agonist at the NMDA receptor in the amygdala, as an agent capable of enhancing extinction learning. Following successful validation of this strategy in animals, six trials in adult humans - and one study in youth with OCD - provide support for DCS dosing as facilitating extinction learning that occurs during exposure-based psychotherapy. However, experts and agencies responsible for regulating drug indications in the US, including the FDA, recognize that safety and efficacy findings in adults should not be routinely extrapolated to children. The present study furthers pilot work on DCS to augment the effects of CBT in children with OCD. The investigators are conducting a double-blind randomized controlled trial, conducted at two sites, to examine the relative benefit of 10 psychotherapy sessions of which sessions 4-10 will be augmented with weight-adjusted doses of DCS (25/50mg) compared to CBT augmented with placebo. 150 youth (ages 7-17) with OCD will be randomly and evenly assigned to one of the two treatment conditions. The primary outcome will be change in OCD symptom severity assessed by independent evaluators. The study recruitment sites are the University of South Florida (USF) and Massachusetts General Hospital/Harvard Medical School (MGH). This study extends the first report of DCS augmentation in youth with anxiety disorder/OCD by conclusively investigating an innovative research approach that manipulates glutamatergic pathways to mediate improved outcomes of exposure-based psychotherapy based upon a translational model of the neurobiology of OCD.
- Conditions
- Obsessive-compulsive Disorder
- Being tested
- Cognitive-behavioral therapy, d-cycloserine, Pill placebo
- Keywords
- Obsessive-compulsive disorder, OCD
- Medical subject headings
- Obsessive-Compulsive Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cognitive-behavioral therapyBehavioural
Also called exposure and response prevention, psychotherapy, counseling
All patients will receive 10 sessions of therapy over 8 weeks using the evidence-based CBT protocol in POTS (2004). Sessions 1-4 will be held twice weekly; sessions 5-10 will be held on a weekly basis. Sessions 1-3 do not include exposures and are devoted to psychoeducation, cognitive therapy, and hierarchy development. Sessions 4-10 involve E/RP exercises specific to each youth.
d-cycloserineDrug
D-cycloserine will be encapsulated into 25mg with identical placebo capsules. Youth will take (1 or 2) DCS or identical placebo capsule 1 hour before sessions 4-10. A 0.7mg/kg dosage corresponds with dosages found to be effective in adult studies (50mg/estimated average adult weight of 70kg=.71mg/kg). Accordingly, doses for this study will be about 0.7mg/kg. Two dosing levels will be used based upon weight ranges to ensure comparable mg/kg levels: children weighing 25-45kg will be given a dosage of 25mg (~0.56-1.0 mg/kg/day), and children ≥46kg will be given 50mg provided in two 25mg capsules (~0.50-1.08mg/kg/day). Doses will be given 1 hour before therapy sessions 4-10.
Pill placeboDrug
The pill placebo will be identical to the active study medication in every respect (e.g., size, shape, number of capsules, etc.).
| Study group | Role | What they receive |
|---|---|---|
| Cognitive-behavioral therapy plus pill placebo | Active comparator | This study arm involves the subject receiving 10 sessions of cognitive behavioral therapy with pill placebo taken 1 hour before the session. Receives: Behavioral: Cognitive-behavioral therapy; Drug: Pill placebo |
| Cognitive-behavioral Therapy plus d-cycloserine | Experimental | This study arm involves the subject receiving 10 sessions of cognitive behavioral therapy with d-cycloserine taken 1 hour before the session. Receives: Behavioral: Cognitive-behavioral therapy; Drug: d-cycloserine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Children's Yale-Brown Obsessive-Compulsive Scale.
The Children's Yale-Brown Obsessive-Compulsive Scale measures the severity of OCD symptoms. There are 10 questions that are summed to arrive at a total score, with higher scores representing more severe OCD symptoms (scores range from 0-40).
Measured: 10 weeks
Secondary outcomes (1)
Clinical Global Impression-Severity
The Clinical Global Impression-Severity involves a trained clinician rating how severe the person's OCD symptoms are on a 0 to 6 scale, with higher scores corresponding to more severe symptoms. This rating only involves a clinician completing a single item.
Measured: 10 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Aug 2011 (estimated)
- Study startJun 2011
- Primary completionJun 2016
- Study completionJun 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Obsessive-compulsive DisorderStudies of the same condition, open and under way.
- More trials run by University of South FloridaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 142 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of South Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Massachusetts General Hospital
- Responsible party
- Sponsor
- Investigators
- Eric Storch, Ph.D., Principal investigator, University of South Florida
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01411774
- Sponsor's protocol ID
- 1R01MH093381
- Status last verified
- Oct 2017
- First submitted
- 10 Jun 2011
- Last updated
- 23 Jan 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
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.
PubMed 20817153
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 1/2 D-cycloserine Augmentation of CBT for Pediatric OCD
- ClinicalTrials.gov ID
- NCT01411774
- Acronym / sponsor ID
- 1R01MH093381
- Conditions
- Obsessive-compulsive Disorder
- Keywords
- Obsessive-compulsive disorder, OCD
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 142 participants (actual)
- Lead sponsor
- University of South FloridaUniversity, hospital or other
- Collaborators
- Massachusetts General Hospital
- Study start
- Jun 2011
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2017 (actual)
- First posted
- 8 Aug 2011 (estimated)
- Results
- Posted 23 Jan 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators are conducting a randomized double-blind placebo-controlled study to assess the efficacy of d-cycloserine augmentation of cognitive-behavioral therapy for the treatment of pediatric obsessive compulsive disorder. This study represents an innovative approach in translating bench research findings into clinical research and testing a new approach for optimizing an effective psychotherapy with a safe non-psychotropic medication.
Detailed description
Obsessive-compulsive disorder (OCD) affects 1-2% of children, runs a chronic course without treatment, and is associated with considerable functional impairment and poor quality of life. Although most patients with OCD respond to cognitive-behavioral therapy (CBT) or pharmacotherapy with a serotonin reuptake inhibitor (SRI), a substantial number of youth remain symptomatic after receiving these therapies. Pharmacological interventions with SRIs are only moderately efficacious, rarely produce remission, may be accompanied by side effects, and may not be an acceptable intervention to some parents. Medication augmentation strategies such as atypical antipsychotics are often used in children with partial response but have concerning metabolic effects and no systematic supporting efficacy or safety data. Although CBT is the gold standard treatment for pediatric OCD, not all patients benefit and the availability of skilled therapists is quite limited. Thus, there is a critical need for interventions to optimize treatment outcome in pediatric OCD. The primary mechanism in CBT is repeated and prolonged exposure to feared situations while abstaining from OCD rituals. This treatment is based on animal models of extinction of conditioned fears. Basic research on the neural circuitry underlying fear extinction led to the examination of d-cycloserine (DCS), a partial agonist at the NMDA receptor in the amygdala, as an agent capable of enhancing extinction learning. Following successful validation of this strategy in animals, six trials in adult humans - and one study in youth with OCD - provide support for DCS dosing as facilitating extinction learning that occurs during exposure-based psychotherapy. However, experts and agencies responsible for regulating drug indications in the US, including the FDA, recognize that safety and efficacy findings in adults should not be routinely extrapolated to children. The present study furthers pilot work on DCS to augment the effects of CBT in children with OCD. The investigators are conducting a double-blind randomized controlled trial, conducted at two sites, to examine the relative benefit of 10 psychotherapy sessions of which sessions 4-10 will be augmented with weight-adjusted doses of DCS (25/50mg) compared to CBT augmented with placebo. 150 youth (ages 7-17) with OCD will be randomly and evenly assigned to one of the two treatment conditions. The primary outcome will be change in OCD symptom severity assessed by independent evaluators. The study recruitment sites are the University of South Florida (USF) and Massachusetts General Hospital/Harvard Medical School (MGH). This study extends the first report of DCS augmentation in youth with anxiety disorder/OCD by conclusively investigating an innovative research approach that manipulates glutamatergic pathways to mediate improved outcomes of exposure-based psychotherapy based upon a translational model of the neurobiology of OCD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cognitive-behavioral therapy plus pill placebo | Active comparator | Behavioral: Cognitive-behavioral therapy, Drug: Pill placeboThis study arm involves the subject receiving 10 sessions of cognitive behavioral therapy with pill placebo taken 1 hour before the session. |
| Cognitive-behavioral Therapy plus d-cycloserine | Experimental | Behavioral: Cognitive-behavioral therapy, Drug: d-cycloserineThis study arm involves the subject receiving 10 sessions of cognitive behavioral therapy with d-cycloserine taken 1 hour before the session. |
Who may qualify
- Ages
- 7 to 17 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Outpatient youth with obsessive-compulsive disorder between the ages 7-17 years.
- A Children's Yale-Brown Obsessive-Compulsive Scale score ≥ 16
- Child has a Full Scale IQ≥85 as assessed on the WASI (within 90% CI).
- English speaking
Key exclusion criteria (11 listed)
- Receiving concurrent psychotherapy or a past adequate trial of CBT for OCD. Families will have the option of discontinuing such services to enroll in the study.
- New Treatments: Initiation of an antidepressant within 12 weeks before study enrollment or an antipsychotic 6 weeks before study enrollment. No new alternative medications, nutritionals or therapeutic diets within 6 weeks of study enrollment.
- Established Treatment changes: Any change in established psychotropic medication (e.g., antidepressants, anxioloytics, stimulant, alpha agonist) within 8 weeks before study enrollment (6 weeks for antipsychotic). Alternative medications must be stable for 6 weeks prior to baseline.
- Current clinically significant suicidality or individuals who have engaged in suicidal behaviors within 6 months will be excluded.
- DSM-IV conduct disorder, autism, bipolar, schizophrenia or schizoaffective disorders; or substance abuse in past 6 months using all available information.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cognitive-behavioral therapyAlso: exposure and response prevention, psychotherapy, counselingAll patients will receive 10 sessions of therapy over 8 weeks using the evidence-based CBT protocol in POTS (2004). Sessions 1-4 will be held twice weekly; sessions 5-10 will be held on a weekly basis. Sessions 1-3 do not include exposures and are devoted to psychoeducation, cognitive therapy, and hierarchy development. Sessions 4-10 involve E/RP exercises specific to each youth. | Behavioural | Cognitive-behavioral Therapy plus d-cycloserine, Cognitive-behavioral therapy plus pill placebo |
| d-cycloserineD-cycloserine will be encapsulated into 25mg with identical placebo capsules. Youth will take (1 or 2) DCS or identical placebo capsule 1 hour before sessions 4-10. A 0.7mg/kg dosage corresponds with dosages found to be effective in adult studies (50mg/estimated average adult weight of 70kg=.71mg/kg). Accordingly, doses for this study will be about 0.7mg/kg. Two dosing levels will be used based upon weight ranges to ensure comparable mg/kg levels: children weighing 25-45kg will be given a dosage of 25mg (~0.56-1.0 mg/kg/day), and children ≥46kg will be given 50mg provided in two 25mg capsules (~0.50-1.08mg/kg/day). Doses will be given 1 hour before therapy sessions 4-10. | Drug | Cognitive-behavioral Therapy plus d-cycloserine |
| Pill placeboThe pill placebo will be identical to the active study medication in every respect (e.g., size, shape, number of capsules, etc.). | Drug | Cognitive-behavioral therapy plus pill placebo |
Primary outcome
Children's Yale-Brown Obsessive-Compulsive Scale.
Time frame: 10 weeks
The Children's Yale-Brown Obsessive-Compulsive Scale measures the severity of OCD symptoms. There are 10 questions that are summed to arrive at a total score, with higher scores representing more severe OCD symptoms (scores range from 0-40).
1 secondary outcome
Clinical Global Impression-Severity
Time frame: 10 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20817153Storch 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Eric Storch, Ph.D. principal investigator
University of South Florida
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cognitive-behavioral therapy and d-cycloserine in people with Obsessive-compulsive Disorder, run by University of South Florida at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Jan 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Children's Yale-Brown Obsessive-Compulsive Scale. (time frame: 10 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01411774, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2018.