Use of an Antibiotic as an Enhancer for the Treatment of Social Phobia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier:
NCT00128401
First received: August 8, 2005
Last updated: February 20, 2013
Last verified: September 2012
  Purpose

This study examines whether an antibiotic, d-cycloserine (DCS), boosts the effectiveness of cognitive behavior therapy (CBT) for social anxiety. CBT has been shown to be effective for the treatment of social anxiety in children and adults, but even after treatment, approximately 40% may remain diagnosable. The antibiotic DCS has been shown to enhance the type of learning that is promoted by exposure therapy, a main component of CBT. This study will test whether DCS can improve the effectiveness of CBT for social anxiety.

All participants will receive 12 weekly CBT sessions. In addition to receiving the CBT, participants will be randomly assigned (similar to a coin toss) to receive either DCS or a placebo (sugar pill). The pill will be taken 1-2 hours prior to each of the 12 CBT sessions. The pill is taken only on the 12 therapy days.

Prior to receiving treatment, participants will be asked to:

  • participate in interviews to assess diagnosis and how they are doing including mood, degree of nervousness and behavior
  • have a physical examination, a urine test, and an electrocardiogram (EKG)
  • undergo tests involving problem-solving and memory
  • prepare and present a speech to a "virtual audience" using virtual reality goggles
  • undergo functional magnetic resonance imaging (fMRI) while performing tasks that involve looking at pictures, remembering things, testing reaction times, and making simple choices

Those who have not improved by the end of the study will be offered standard antianxiety medication treatment for 1 to 3 months. If a participant does not wish to take medication, study clinicians will help him/her locate psychological care in the community. Participants will be asked to complete a follow-up assessment 3 months after their last CBT session.


Condition Intervention Phase
Phobic Disorders
Anxiety
Social Phobia
Drug: D-Cycloserine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Effect of D-Cycloserine on Treatment of Social Phobia

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Clinical Global Improvement (CGI-S) scale Liebowitz Social Anxiety Scale (LSAS) [ Time Frame: Conclusion of 12 sessions (CBT + DCS/Placebo) and 3 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Examine changes during tx in emotional processes previously shown to distinguish socially anxious individuals from healthy controls. [ Time Frame: Conclusion of 12 sessions ] [ Designated as safety issue: No ]

Enrollment: 50
Study Start Date: August 2005
Study Completion Date: August 2012
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: D-Cycloserine
    N/A
Detailed Description:

Social phobia afflicts between 3%-15% of the US population. As such, it is a particularly common debilitating psychiatric disorder. Like many anxiety disorders, social phobia typically arises during adolescence. Treatment has consisted of medication or cognitive behavioral therapy (CBT). Selective Serotonin Reuptake Inhibitors (SSRIs) represent the first-line pharmacological treatment both in adults as well as adolescents (APA Treatment Guidelines 2004). Similarly, CBT significantly improves outcome in both age groups. This treatment consists of psychoeducation, exposure therapy, and cognitive restructuring. While both treatments produce clinically meaningful benefits, most patients exhibiting positive responses to these treatments continue to exhibit marked residual symptoms, if not full-blown anxiety disorders. Thus, there is great need for treatment advances.

Intense fear of social scrutiny represents a core component of social phobia, and extinction of this fear represents the goal of exposure therapy during CBT (Cohn and Hope). Finding treatments that facilitate extinction is of paramount importance. In animals, extinction involves an active learning process that is blocked by glutamatergic NMDA antagonists and facilitated by NMDA agonists. Specifically, administration of D-cycloserine (DCS), a partial agonist at the glycine modulatory site on the NMDA receptor, produces a dose-dependent facilitation of extinction in the rat. As such, DCS might facilitate extinction during exposure-based CBT. Indeed, Ressler (Ressler et al 2004) recently reported preliminary data from a clinical trial supporting this hypothesis.

We will examine the degree to which DCS treatment can augment the clinical response in social phobia to CBT-exposure-based therapy. Specifically, we will study two groups of individuals with social phobia, both of whom will receive CBT. One group will receive placebo; a second group will receive 50 mg of D-cycloserine 1-2 hours before each exposure therapy session. We hypothesize that compared to placebo, DCS will produce greater reductions in social anxiety symptoms following CBT treatment. Finally, given that chronic social anxiety disorder virtually always begins during childhood, it is particularly vital to develop early interventions for the disorder. Accordingly, our trial will examine both adolescents and adults with the disorder.

  Eligibility

Ages Eligible for Study:   8 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

    1. Subjects between 8 yrs of age (preadolescents) and under 55 yrs of age.
    2. Subjects medically healthy.
    3. Able to give informed consent.
    4. Not on psychotropic meds for a minimum of 6 weeks for fluoxetine; a minimum of 1 week for PRN benzodiazepines and beta blockers, and a minimum of 3 weeks for all other psychotropic meds.
    5. Subjects diagnosed with DSM IV symptoms of social phobia, generalized or specific type.

EXCLUSION CRITERIA:

  1. Current major depressive disorder.
  2. Lifetime diagnosis of psychotic disorder, bipolar disorder, eating disorder, mental retardation, substance or alcohol dependence (other than nicotine); active suicidal ideation.
  3. Current or lifetime history of a neurological disorder (other than tic disorders, febrile seizures of infancy), seizure disorder.
  4. Any unstable medical condition.
  5. Use of any psychoactive substance in the past 30 days.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00128401

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Jennifer A Cameron, C.R.N.P. National Institute of Mental Health (NIMH)
  More Information

Additional Information:
Publications:
Responsible Party: National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )
ClinicalTrials.gov Identifier: NCT00128401     History of Changes
Other Study ID Numbers: 050198, 05-M-0198
Study First Received: August 8, 2005
Last Updated: February 20, 2013
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Cognitive
Behavioral
Adolescent
Therapy
Extinction
Social Phobia

Additional relevant MeSH terms:
Anxiety Disorders
Phobic 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 April 15, 2014