D-Cycloserine Enhancement of Exposure in Social Phobia

Phase 4

Completed

• Conditions: Social Anxiety Disorder
• Interventions: Behavioral: Cognitive Behavioral Group Therapy (CBGT); Drug: Placebo; Drug: D-Cycloserine

• Registration Number: NCT00633984
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

The purpose of this study is to test a drug called d-cycloserine to see if it can help people with a condition called social phobia. Social phobia is also called "social anxiety disorder." Social phobia is a constant fear of social or performance situations. Social situations include group gatherings of any kind. Performance situations might include times when a person would have to do something in public, such as speak up in class or at a meeting. A person with this condition worries about being embarrassed, or about other people's opinions. People with social phobia usually feel extremely anxious (nervous and worried) about being the focus of attention. They often avoid social and performance situations. This behavior can have a negative effect on the quality of their lives and relationships.

In this study, we want to find out if d-cycloserine can help control social phobia when the drug is added to the standard treatment for this condition. The standard treatment is cognitive-behavior therapy (CBT). CBT is a form of talk therapy involving discussion with a therapist, along with practicing the feelings or events that the person finds frightening.

Detailed Description

Inclusion criteria:

1. Age 18 or older

2. Primary diagnosis of SAD

3. Physical examination, electrocardiogram, and laboratory findings without clinically significant abnormalities.

4. Willingness and ability to comply with the requirements of the study protocol.

Diagnostic Exclusion Criteria:

1. A lifetime history of bipolar disorder, schizophrenia, psychosis, delusional disorders or obsessive-compulsive disorder; an eating disorder in the past 6 months; organic brain syndrome, mental retardation or other cognitive dysfunction that could interfere with capacity to engage in therapy; a history of substance or alcohol abuse or dependence (other than nicotine) in the last 6 months or otherwise unable to commit to refraining from alcohol use during the acute period of study participation.

2. Patients with posttraumatic stress disorder within the past 6 months are excluded. Entry of patients with other mood or anxiety disorders will be permitted if the social anxiety disorder is judged to be the predominant disorder, in order to increase accrual of a clinically relevant sample. Patients with significant suicidal ideation (MADRS item 10 score \> 3) or who have enacted suicidal behaviors within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.

3. Patients must be off concurrent psychotropic medication (e.g., antidepressants, anxiolytics, beta blockers) for at least 2 weeks prior to initiation of randomized treatment.

4. Significant personality dysfunction likely to interfere with study participation.

5. Serious medical illness or instability for which hospitalization may be likely within the next year.

6. Patients with a current or past history of seizures

7. Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception (e.g., IUD, oral contraceptives, barrier devices, condoms and foam, or implanted progesterone rods stabilized for at least 3 months).

8. Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of the GSAD is excluded. Prohibited psychotherapy includes CBT or psychodynamic therapy focusing on exploring specific, dynamic causes of the phobic symptomatology and provides management skills. General supportive therapy initiated \> 3 months prior is acceptable.

9. Prior non-response to adequately-delivered exposure (i.e., as defined by the patient's report of receiving specific and regular exposure assignments as part of a previous treatment) will exclude participants from the study.

10. Patients with a history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment.

11. Patients receiving isoniazid.

12. Patients unable to understand study procedures and participate in the informed consent process.

Study Timeline

• Study Start: 2007-03
• Study First Submitted: 2008-03-04
• Study First Submitted QC: 2008-03-04
• Study First Posted: 2008-03-12
• Primary Completion: 2012-03
• Study Completion: 2012-09
• Results First Submitted: 2014-01-02
• Status Verified: 2014-04
• Results First Submitted QC: 2014-04-14
• Last Update Submitted: 2014-04-14
• Results First Posted: 2014-05-14
• Last Update Posted: 2014-05-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 169

Inclusion Criteria

1. Male or female outpatients > 18 years of age with a primary psychiatric diagnosis (designated by the patient as the most important source of current distress) of generalized social anxiety disorder (GSAD) as defined by DSM-IV criteria.
2. A total score > 60 on the LSAS.
3. Physical examination, electrocardiogram, and laboratory findings without clinically significant abnormalities.
4. Willingness and ability to comply with the requirements of the study protocol.

Exclusion Criteria

1. A lifetime history of bipolar disorder, schizophrenia, psychosis, delusional disorders or obsessive-compulsive disorder; an eating disorder in the past 6 months; organic brain syndrome, mental retardation or other cognitive dysfunction that could interfere with capacity to engage in therapy; a history of substance or alcohol abuse or dependence (other than nicotine) in the last 6 months or otherwise unable to commit to refraining from alcohol use during the acute period of study participation.
2. Patients with posttraumatic stress disorder within the past 6 months are excluded. Entry of patients with other mood or anxiety disorders will be permitted if the social anxiety disorder is judged to be the predominant disorder, in order to increase accrual of a clinically relevant sample. Patients with significant suicidal ideation (MADRS item 10 score > 3) or who have enacted suicidal behaviors within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.
3. Patients must be off concurrent psychotropic medication (e.g., antidepressants, anxiolytics, beta blockers) for at least 2 weeks prior to initiation of randomized treatment.
4. Significant personality dysfunction likely to interfere with study participation.
5. Serious medical illness or instability for which hospitalization may be likely within the next year.
6. Patients with a current or past history of seizures
7. Pregnant women, lactating women, and women of childbearing potential who are not using medically accepted forms of contraception (e.g., IUD, oral contraceptives, barrier devices, condoms and foam, or implanted progesterone rods stabilized for at least 3 months).
8. Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of the GSAD is excluded. Prohibited psychotherapy includes CBT or psychodynamic therapy focusing on exploring specific, dynamic causes of the phobic symptomatology and provides management skills. General supportive therapy initiated > 3 months prior is acceptable.
9. Prior non-response to adequately-delivered exposure (i.e., as defined by the patient's report of receiving specific and regular exposure assignments as part of a previous treatment) will exclude participants from the study.
10. Patients with a history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment.
11. Patients receiving isoniazid.
12. Patients unable to understand study procedures and participate in the informed consent process.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cognitive Behavioral Group Therapy + D-Cycloserine	Cognitive Behavioral Group Therapy (CBGT)	Participants received Cognitive Behavioral Group Therapy and 50mg D-Cycloserine.
Cognitive Behavioral Group Therapy + Placebo	Cognitive Behavioral Group Therapy (CBGT)	Participants received Cognitive Behavioral Group Therapy and 50mg Placebo.
Cognitive Behavioral Group Therapy + Placebo	Placebo	Participants received Cognitive Behavioral Group Therapy and 50mg Placebo.
Cognitive Behavioral Group Therapy + D-Cycloserine	D-Cycloserine	Participants received Cognitive Behavioral Group Therapy and 50mg D-Cycloserine.

Primary Outcome Measures

Name	Time	Method
Liebowitz Social Anxiety Scale (LSAS)	Week 13	The Liebowitz Social Anxiety Scale (LSAS) is a 24-item measure designed to assess both fear and avoidance of social and performance situations occurring in the last week. Each item is rated from 0-3 for both fear and avoidance with a possible score of 144; 55-65 Moderate social phobia, 65-80 Marked social phobia, 80-95 Severe social phobia, and Greater than 95 - Very severe social phobia. Remission was defined as a score of \< 30 on the Liebowitz Social Anxiety Scale
CGI - Clinical Global Impression of Improvement	Week 13	The Clinician Global Impression-Improvement Scale (CGI-I) is a clinician-rated instrument used to assess global severity of symptoms. The CGI-I ranges from 1 ("very much improved") to 7 ("very much worse"). Response and remission was defined as an improvement score of 1 ("very much improved") or 2 ("much improved") on the CGI-I.

Trial Locations

Locations (1)

Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States