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

Study Overview
=================
Brief Summary
-----------------
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.

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.

Official Title
-----------------
Effect of D-Cycloserine on Treatment of Social Phobia

Conditions
-----------------
Phobic Disorders, Anxiety, Social Phobia

Intervention / Treatment
-----------------
* Drug: D-Cycloserine
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
INCLUSION CRITERIA: Subjects between 8 yrs of age (preadolescents) and under 55 yrs of age. Subjects medically healthy. Able to give informed consent. 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. Subjects diagnosed with DSM IV symptoms of social phobia, generalized or specific type. EXCLUSION CRITERIA: Current major depressive disorder. Lifetime diagnosis of psychotic disorder, bipolar disorder, eating disorder, mental retardation, substance or alcohol dependence (other than nicotine); active suicidal ideation. Current or lifetime history of a neurological disorder (other than tic disorders, febrile seizures of infancy), seizure disorder. Any unstable medical condition. Use of any psychoactive substance in the past 30 days.

Ages Eligible for Study
-----------------
Minimum Age: 8 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: D-Cycloserine<br>An antibiotic, d-cycloserine (DCS) was given to one group and the group is evaluated to see if the drug boosts the effectiveness of cognitive behavior therapy (CBT) for social anxiety. | Drug: D-Cycloserine<br> <br> |
| Placebo Comparator: Placebo<br>Another group was given the placebo and tested for effectiveness of cognitive behavior therapy (CBT) for social anxiety. | Drug: Placebo<br> <br> |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Global Improvement (CGI-S) Scale | Symptom severity and improvement was assessed using the Clinical Global Impressions scale (CGI). It is a 2-item clinician-administered instrument that measures the patients' illness severity and global improvement. The minimum value for the CGI is 1=Normal, not at all ill and the maximum value is 7=Among the most extremely ill patients. | 12 weeks post baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liebowitz Social Anxiety Scale (LSAS) | Social anxiety symptoms were assessed using the Liebowitz Social Anxiety Scale (LSAS). It is a 24-item self-report instrument that measures overall social anxiety fear and avoidance symptoms. This is the baseline assessment. The 24 items are each rated twice, from a 0 to 3 scale, with 0 indicated no level of symptom and 3 indicating a high level of the system. One rating is for anxiety, and the other is for avoidance. Thus, the lowest possible score is 0, and the highest possible score is 144. The total score represents the simple sum of all 48 ratings. | 12 weeks post baseline | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Cognitive, Behavioral, Adolescent, Therapy, Extinction, Social Phobia