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Exposure, D-Cycloserine Enhancement, and Genetic Modulators in Panic Disorder (DCSPanic)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified April 2013 by Boston University.
Recruitment status was:  Active, not recruiting
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
Information provided by (Responsible Party):
Michael Otto, Boston University Identifier:
First received: November 13, 2008
Last updated: May 23, 2013
Last verified: April 2013
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.

Condition Intervention Phase
Panic Disorder
Drug: d-cycloserine
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Exposure, D-Cycloserine Enhancement, and Genetic Modulators in Panic Disorder

Resource links provided by NLM:

Further study details as provided by Boston University:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • (1) remission status (2) anxiety sensitivity (3) Q-LES-Q, (4) LIFE-RIFT, MADRS, and non-panic anxiety symptom [ Time Frame: same as above ]

Estimated Enrollment: 192
Study Start Date: April 2008
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I
DCS-augmented CBT
Drug: d-cycloserine
Other Name: DCS
Placebo Comparator: II
placebo-augmented CBT
Drug: placebo

Detailed 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.


Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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
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Please refer to this study by its identifier: 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 University
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Boston University
National Institute on Drug Abuse (NIDA)
National Institute of Mental Health (NIMH)
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
  More Information

Responsible Party: Michael Otto, Ph.D., Boston University Identifier: NCT00790868     History of Changes
Other Study ID Numbers: R01MH081116 ( US NIH Grant/Contract Award Number )
Study First Received: November 13, 2008
Last Updated: May 23, 2013

Keywords provided by Boston University:
Panic Disorder
Cognitive Behavioral Therapy

Additional relevant MeSH terms:
Panic Disorder
Pathologic Processes
Anxiety Disorders
Mental Disorders
Anti-Infective Agents, Urinary
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Renal Agents
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Antitubercular Agents
Anti-Bacterial Agents
Molecular Mechanisms of Pharmacological Action processed this record on May 25, 2017