Exposure, D-Cycloserine Enhancement, and Genetic Modulators in Panic Disorder (DCSPanic)
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|ClinicalTrials.gov Identifier: NCT00790868|
Recruitment Status : Completed
First Posted : November 14, 2008
Results First Posted : March 7, 2018
Last Update Posted : March 7, 2018
|Condition or disease||Intervention/treatment||Phase|
|Panic Disorder||Drug: d-cycloserine Drug: placebo||Phase 2|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||180 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Participant, Investigator)|
|Official Title:||Exposure, D-Cycloserine Enhancement, and Genetic Modulators in Panic Disorder|
|Actual Study Start Date :||April 2008|
|Actual Primary Completion Date :||August 2014|
|Actual Study Completion Date :||August 2014|
Other Name: DCS
Placebo Comparator: Placebo
- 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.
- Depression Severity [ Time Frame: Baseline, Tx Endpoint, Each of 4 follow-up assessments ]Depression severity was assessed with the MADRS, with scores ranging from 0 to 60. Higher scores indicate greater depression.
- Quality of Life Ratings [ Time Frame: Baseline, Tx Endpoint, Each of 4 follow-up assessments ]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.
- Role Functioning [ Time Frame: Baseline, Tx Endpoint, Each of 4 follow-up assessments ]LIFE-RIFT. For this clinician-rated measure, total scores range from 0 to 20, with higher scores indicating greater impairment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00790868
|United States, Connecticut|
|Institute of Living|
|Hartford, Connecticut, United States, 06106|
|United States, Illinois|
|Rush University Medical Center|
|Chicago, Illinois, United States, 60612|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Boston, Massachusetts, United States, 02215|
|Study Chair:||Michael W Otto, PhD||Boston University|
|Principal Investigator:||David F Tolin, PhD||Institute of Living|
|Principal Investigator:||Mark H Pollack, MD||Rush University Medical Center|