Panic DisorderPhase 2DCSPanicNCT00790868
Exposure, D-Cycloserine Enhancement, and Genetic Modulators in Panic Disorder
A Phase 2 study testing d-cycloserine in people with Panic Disorder, run by Boston University Charles River Campus at 4 sites in United States.
Trial summary
This is a 5-year double blind, randomized, controlled, trial conducted at three treatment sites, aimed at showing the acute and longer-term effects of DCS augmentation of exposure-based CBT for panic disorder relative to placebo augmentation. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Panic Disorder
- What is being tested?
- d-cycloserine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 180 participants
- Where
- 4 sitesUnited States
- Study dates
- Apr 2008to Aug 2014
- Phase
- Phase 2
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female outpatients > 18 years of age with a primary psychiatric diagnosis of panic disorder with or without agoraphobia
- CGI-severity score of 4 or higher
- Physical examination and laboratory findings without clinically significant abnormalities
- Off concurrent psychotropic medication for at least 2 weeks prior to initiation of randomized treatment, OR stable on current medication for a minimum of 6 weeks and willing to maintain a stable dose
- Willingness and ability to comply with the requirements of the study protocol
Who cannot join
- Agoraphobia sufficiently severe as to limit patient's ability to travel to and participate in weekly sessions Posttraumatic stress disorder, substance use disorder, eating disorder, or organic mental disorder within the past 6 months
- Lifetime history of psychotic disorder, bipolar disorder, or developmental disorder
- Significant suicidal ideation or suicidal behaviors within the past 6 months
- Significant personality dysfunction likely to interfere with study participation
- Serious medical illness or instability for which hospitalization may be likely within the next year
- Patients with a current or past history of seizures (other than febrile seizures in childhood)
Show all 9Show fewer
- Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception
- Concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of the panic disorder other than general supportive therapy initiated at least 3 months prior to study
- Prior adequate trial of CBT for panic disorder
Trial locations and contacts
4 sites in 1 country.
United States4 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Boston University
Boston, Massachusetts, 02215
Rush University Medical Center
Chicago, Illinois, 60612
Institute of Living
Hartford, Connecticut, 06106
About this study
This is a 5-year double blind, randomized, controlled, trial conducted at three treatment sites, aimed at showing the acute and longer-term effects of DCS augmentation of exposure-based CBT for panic disorder relative to placebo augmentation. By demonstrating that DCS can enhance the results of even a brief treatment strategy, the investigators are seeking to validate an approach that fits well with the practice limitations and applications of CBT in effectiveness studies.
Read the detailed description
In this application, the investigators propose to further validate and expand upon one of the apparent striking successes of translational research. Specifically, basic research on the neural circuitry underlying fear extinction led to the examination of d-cycloserine (DCS), a partial agonist of the NMDA receptor in the amygdala, as an agent capable of enhancing extinction learning (Davis et al., 2006; Davis et al., in press). Following successful validation of this strategy in the animal laboratory (see Ledgerwood et al., 2005; Richardson et al., 2004), Ressler et al. (2004) showed that single doses of d-cycloserine (DCS) could enhance extinction in a human exposure paradigm for height phobic adults. This exciting initial finding was replicated by this research team for the treatment of social anxiety disorder (Hofmann et al., 2006), as well as an initial pilot study of the treatment of panic disorder (Tolin et al., 2006). As discussed by Anderson and Insel (2006), these findings have the potential to foster significant advances in the treatment of anxiety disorders. The present study represents the further application of DCS for augmenting the effects of exposure-based cognitive-behavior therapy (CBT), now applied to the treatment of panic disorder with or without agoraphobia.
In the current application, the investigators propose a five-year study to show the acute and longer-term effects of DCS augmentation of exposure-based CBT relative to placebo augmentation. This study is noteworthy for the use of a brief treatment strategy that has been shown to be successful in previous trials (e.g., Clark et al., 1999; Roy-Byrne et al., 2005) and has served as the basis for the DCS augmentation effect seen in a pilot study for this application. By demonstrating that DCS can enhance the results of even a brief treatment strategy, the investigators are seeking to validate an approach that fits well with the practice limitations and applications of CBT in effectiveness studies (e.g., Katon et al., 2006; Roy-Byrne et al. 2005). Furthermore, by studying the genetic predictors of the overall response to CBT, and DCS augmentation in particular, the investigators hope to further elucidate the nature of DCS augmentation and the selection of particularly responsive subgroups of patients in need. This agenda is in accords with "the ultimate goal of personalized therapy: identifying individual patterns of pathophysiology that indicate which pharmacological or behavioral treatment will be most useful for any individual patient" (Anderson \& Insel, 2006, p. 320).
The study design is a double blind, randomized, controlled, trial conducted at three treatment sites. Patient with panic disorder will randomly receive DCS or placebo 1 hour prior to sessions 3-5 of a 5-session CBT protocol that includes 2 additional booster sessions over the course of follow-up. Patients will be enrolled over 5 years with the identical treatment protocol followed at each of the sites. Sites will nonetheless differ with respect to study management and analysis procedures.
- Conditions
- Panic Disorder
- Being tested
- d-cycloserine, placebo
- Keywords
- Panic Disorder, Anxiety, D-cycloserine, DCS, Cognitive Behavioral Therapy, CBT
- Medical subject headings
- Panic Disorder, Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
d-cycloserineDrug
Also called DCS
50mg
placeboDrug
50mg
| Study group | Role | What they receive |
|---|---|---|
| D-cycloserine | Experimental | DCS-augmented CBT Receives: Drug: d-cycloserine |
| Placebo | Placebo comparator | placebo-augmented CBT Receives: Drug: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Panic Disorder Severity Scale (PDSS)
The percent change in PDSS score from baseline to the relevant assessment points is the continuous primary outcome measure. The PDSS consists of seven items, each rated on a 0 to 4 scale (0 denoting none, and higher ratings reflecting greater degrees of symptom severity; for a possible range in scores from 0 to 28). In the tabular data below we present the total scores (sum of items).
Measured: baseline, mid-TX, post-TX, follow-up visits 1-4
Remission Status
Remission status will be used as the primary categorical outcome variable. The CGI-S was used in determining whether patients met the "CGI-S of 1 or 2" component of the "remission status" criteria (i.e., zero panic attacks and CGI-S of 1 or 2 at endpoint). No values are missing because remission must be confirmed; missing status is assigned to disorder status. Hence results are for the full randomized sample.
Measured: Pre-treatment, Post-Treatment, and each follow-up sessions
Secondary outcomes (3)
Depression Severity
Depression severity was assessed with the MADRS, with scores ranging from 0 to 60. Higher scores indicate greater depression.
Measured: Baseline, Tx Endpoint, Each of 4 follow-up assessments
Quality of Life Ratings
Quality of life as assessed by the Q-LES-Q. Scores range from 14-70 for total raw score, higher scores indicate higher quality of life ratings.
Measured: Baseline, Tx Endpoint, Each of 4 follow-up assessments
Role Functioning
LIFE-RIFT. For this clinician-rated measure, total scores range from 0 to 20, with higher scores indicating greater impairment
Measured: Baseline, Tx Endpoint, Each of 4 follow-up assessments
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Nov 2008 (estimated)
- Study startApr 2008
- Primary completionAug 2014
- Study completionAug 2014
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 Panic DisorderStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 180 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boston University Charles River Campus
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Michael Otto, Boston University Charles River Campus
- Investigators
- Michael W Otto, PhD, Study chair, Boston UniversityDavid F Tolin, PhD, Principal investigator, Institute of LivingMark H Pollack, MD, Principal investigator, Rush University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00790868
- Sponsor's protocol ID
- R01MH081116
- Other IDs
- R01MH081116
- Acronym
- DCSPanic
- Status last verified
- Feb 2018
- First submitted
- 13 Nov 2008
- Last updated
- 7 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Otto MW, Pollack MH, Dowd SM, Hofmann SG, Pearlson G, Szuhany KL, Gueorguieva R, Krystal JH, Simon NM, Tolin DF. RANDOMIZED TRIAL OF D-CYCLOSERINE ENHANCEMENT OF COGNITIVE-BEHAVIORAL THERAPY FOR PANIC DISORDER. Depress Anxiety. 2016 Aug;33(8):737-45. doi: 10.1002/da.22531. Epub 2016 Jun 17.
PubMed 27315514
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exposure, D-Cycloserine Enhancement, and Genetic Modulators in Panic Disorder
- ClinicalTrials.gov ID
- NCT00790868
- Acronym / sponsor ID
- DCSPanic / R01MH081116
- Conditions
- Panic Disorder
- Keywords
- Panic Disorder, Anxiety, D-cycloserine, DCS, Cognitive Behavioral Therapy, CBT
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 180 participants (actual)
- Lead sponsor
- Boston University Charles River CampusUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA), National Institute of Mental Health (NIMH)
- Study start
- Apr 2008 (actual)
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 14 Nov 2008 (estimated)
- Results
- Posted 7 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a 5-year double blind, randomized, controlled, trial conducted at three treatment sites, aimed at showing the acute and longer-term effects of DCS augmentation of exposure-based CBT for panic disorder relative to placebo augmentation. By demonstrating that DCS can enhance the results of even a brief treatment strategy, the investigators are seeking to validate an approach that fits well with the practice limitations and applications of CBT in effectiveness studies.
Detailed description
In this application, the investigators propose to further validate and expand upon one of the apparent striking successes of translational research. Specifically, basic research on the neural circuitry underlying fear extinction led to the examination of d-cycloserine (DCS), a partial agonist of the NMDA receptor in the amygdala, as an agent capable of enhancing extinction learning (Davis et al., 2006; Davis et al., in press). Following successful validation of this strategy in the animal laboratory (see Ledgerwood et al., 2005; Richardson et al., 2004), Ressler et al. (2004) showed that single doses of d-cycloserine (DCS) could enhance extinction in a human exposure paradigm for height phobic adults. This exciting initial finding was replicated by this research team for the treatment of social anxiety disorder (Hofmann et al., 2006), as well as an initial pilot study of the treatment of panic disorder (Tolin et al., 2006). As discussed by Anderson and Insel (2006), these findings have the potential to foster significant advances in the treatment of anxiety disorders. The present study represents the further application of DCS for augmenting the effects of exposure-based cognitive-behavior therapy (CBT), now applied to the treatment of panic disorder with or without agoraphobia.
In the current application, the investigators propose a five-year study to show the acute and longer-term effects of DCS augmentation of exposure-based CBT relative to placebo augmentation. This study is noteworthy for the use of a brief treatment strategy that has been shown to be successful in previous trials (e.g., Clark et al., 1999; Roy-Byrne et al., 2005) and has served as the basis for the DCS augmentation effect seen in a pilot study for this application. By demonstrating that DCS can enhance the results of even a brief treatment strategy, the investigators are seeking to validate an approach that fits well with the practice limitations and applications of CBT in effectiveness studies (e.g., Katon et al., 2006; Roy-Byrne et al. 2005). Furthermore, by studying the genetic predictors of the overall response to CBT, and DCS augmentation in particular, the investigators hope to further elucidate the nature of DCS augmentation and the selection of particularly responsive subgroups of patients in need. This agenda is in accords with "the ultimate goal of personalized therapy: identifying individual patterns of pathophysiology that indicate which pharmacological or behavioral treatment will be most useful for any individual patient" (Anderson \& Insel, 2006, p. 320).
The study design is a double blind, randomized, controlled, trial conducted at three treatment sites. Patient with panic disorder will randomly receive DCS or placebo 1 hour prior to sessions 3-5 of a 5-session CBT protocol that includes 2 additional booster sessions over the course of follow-up. Patients will be enrolled over 5 years with the identical treatment protocol followed at each of the sites. Sites will nonetheless differ with respect to study management and analysis procedures.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| D-cycloserine | Experimental | Drug: d-cycloserineDCS-augmented CBT |
| Placebo | Placebo comparator | Drug: placeboplacebo-augmented CBT |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female outpatients > 18 years of age with a primary psychiatric diagnosis of panic disorder with or without agoraphobia
- CGI-severity score of 4 or higher
- Physical examination and laboratory findings without clinically significant abnormalities
- Off concurrent psychotropic medication for at least 2 weeks prior to initiation of randomized treatment, OR stable on current medication for a minimum of 6 weeks and willing to maintain a stable dose
- Willingness and ability to comply with the requirements of the study protocol
Key exclusion criteria (9 listed)
- Agoraphobia sufficiently severe as to limit patient's ability to travel to and participate in weekly sessions Posttraumatic stress disorder, substance use disorder, eating disorder, or organic mental disorder within the past 6 months
- Lifetime history of psychotic disorder, bipolar disorder, or developmental disorder
- Significant suicidal ideation or suicidal behaviors within the past 6 months
- Significant personality dysfunction likely to interfere with study participation
- Serious medical illness or instability for which hospitalization may be likely within the next year
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 |
|---|---|---|
| d-cycloserineAlso: DCS50mg | Drug | D-cycloserine |
| placebo50mg | Drug | Placebo |
Primary outcome
Panic Disorder Severity Scale (PDSS)
Time frame: baseline, mid-TX, post-TX, follow-up visits 1-4
The percent change in PDSS score from baseline to the relevant assessment points is the continuous primary outcome measure. The PDSS consists of seven items, each rated on a 0 to 4 scale (0 denoting none, and higher ratings reflecting greater degrees of symptom severity; for a possible range in scores from 0 to 28). In the tabular data below we present the total scores (sum of items).
Remission Status
Time frame: Pre-treatment, Post-Treatment, and each follow-up sessions
Remission status will be used as the primary categorical outcome variable. The CGI-S was used in determining whether patients met the "CGI-S of 1 or 2" component of the "remission status" criteria (i.e., zero panic attacks and CGI-S of 1 or 2 at endpoint). No values are missing because remission must be confirmed; missing status is assigned to disorder status. Hence results are for the full randomized sample.
3 secondary outcomes
Depression Severity
Time frame: Baseline, Tx Endpoint, Each of 4 follow-up assessments
Quality of Life Ratings
Time frame: Baseline, Tx Endpoint, Each of 4 follow-up assessments
Role Functioning
Time frame: Baseline, Tx Endpoint, Each of 4 follow-up assessments
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 27315514Otto MW, Pollack MH, Dowd SM, Hofmann SG, Pearlson G, Szuhany KL, Gueorguieva R, Krystal JH, Simon NM, Tolin DF. RANDOMIZED TRIAL OF D-CYCLOSERINE ENHANCEMENT OF COGNITIVE-BEHAVIORAL THERAPY FOR PANIC DISORDER. Depress Anxiety. 2016 Aug;33(8):737-45. doi: 10.1002/da.22531. Epub 2016 Jun 17.
- Individual participant dataSharing planned: No
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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.
Michael W Otto, PhD study chair
Boston University
David F Tolin, PhD principal investigator
Institute of Living
Mark H Pollack, MD principal investigator
Rush University Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing d-cycloserine in people with Panic Disorder, run by Boston University Charles River Campus at 4 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 5 inclusion and 9 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 7 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 7 Mar 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?
Panic Disorder Severity Scale (PDSS) (time frame: baseline, mid-TX, post-TX, follow-up visits 1-4). The study lists 2 primary outcomes in all. 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 NCT00790868, 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 7 Mar 2018.