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

Information source: Boston University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Panic Disorder

Intervention: d-cycloserine (Drug); placebo (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: Boston University

Official(s) and/or principal investigator(s):
Michael W Otto, PhD, Study Chair, Affiliation: Boston University
David F Tolin, PhD, Principal Investigator, Affiliation: Institute of Living
Mark H Pollack, MD, Principal Investigator, Affiliation: Rush University Medical Center

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. 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.

Clinical Details

Official title: Exposure, D-Cycloserine Enhancement, and Genetic Modulators in Panic Disorder

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: 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.

Secondary outcome: (1) remission status (2) anxiety sensitivity (3) Q-LES-Q, (4) LIFE-RIFT, MADRS, and non-panic anxiety symptom

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

Minimum age: 18 Years. Maximum age: 80 Years. Gender(s): Both.

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

Locations and Contacts

Institute of Living, Hartford, Connecticut 06106, United States

Rush University Medical Center, Chicago, Illinois 60612, United States

Boston University, Boston, Massachusetts 02215, United States

Massachusetts General Hospital, Boston, Massachusetts 02114, United States

Additional Information

Starting date: April 2008
Last updated: May 23, 2013

Page last updated: August 23, 2015

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