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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Information provided by (Responsible Party):
Michael Otto, Boston University
ClinicalTrials.gov Identifier:
NCT00790868
First received: November 13, 2008
Last updated: May 23, 2013
Last verified: April 2013
  Purpose

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
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, 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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]

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
50mg
Other Name: DCS
Placebo Comparator: II
placebo-augmented CBT
Drug: placebo
50mg

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00790868

Locations
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
Boston University
Boston, Massachusetts, United States, 02215
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Boston University
Investigators
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

No publications provided

Responsible Party: Michael Otto, Ph.D., Boston University
ClinicalTrials.gov Identifier: NCT00790868     History of Changes
Other Study ID Numbers: R01 MH081116, R01MH081116
Study First Received: November 13, 2008
Last Updated: May 23, 2013
Health Authority: United States: Federal Government

Keywords provided by Boston University:
Panic Disorder
Anxiety
D-cycloserine
DCS
Cognitive Behavioral Therapy
CBT

Additional relevant MeSH terms:
Panic Disorder
Anxiety Disorders
Mental Disorders
Cycloserine
Anti-Infective Agents, Urinary
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Renal Agents
Antibiotics, Antitubercular
Anti-Bacterial Agents
Antitubercular Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014