Exposure, D-Cycloserine Enhancement, and Genetic Modulators in Panic Disorder
This trial is active, not recruiting.
|Collaborator||National Institute on Drug Abuse (NIDA)|
|Start date||April 2008|
|End date||March 2014|
|Trial size||192 participants|
|Trial identifier||NCT00790868, R01 MH081116, R01MH081116|
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, we are seeking to validate an approach that fits well wtih teh practice limitations and applications of CBT in effectiveness studies.
|United States||No locations recruiting|
|Other Countries||No locations recruiting|
|Hartford, CT||Institute of Living||no longer recruiting|
|Chicago, IL||Rush University Medical Center||no longer recruiting|
|Boston, MA||Boston University||no longer recruiting|
|Boston, MA||Massachusetts General Hospital||no longer recruiting|
|Endpoint classification||efficacy study|
|Intervention model||parallel assignment|
|Masking||double blind (subject, investigator)|
The change in PDSS score from baseline to the relevant assessment points is the continuous primary outcome measure. Remission status will be used as the primary categorical outcome variable.
time frame: mid, post, follow-up
(1) remission status (2) anxiety sensitivity (3) Q-LES-Q, (4) LIFE-RIFT, MADRS, and non-panic anxiety symptom
time frame: same as above
Male or female participants from 18 years up to 80 years old.
Inclusion Criteria: - 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 Exclusion Criteria: - 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) - 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
|Official title||Exposure, D-Cycloserine Enhancement, and Genetic Modulators in Panic Disorder|
|Principal investigator||David F Tolin, PhD|
|Description||In this application, we 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 our research team for the treatment of social anxiety disorder (Hofmann et al., 2006), as well as an initial pilot study by our research team of the treatment of panic disorder (Tolin et al., 2006; see Preliminary Studies). 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, we propose a five-year study to show the acute and longer-term effects of DCS augmentation of exposure-based CBT relative to placebo augmentation. Our 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 (see Preliminary Studies). By demonstrating that DCS can enhance the results of even a brief treatment strategy, we 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, we 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). Our study design calls for 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. We will enter a total of 192 patients 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.|
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