Clinical trial NCT00633984: D-Cycloserine Enhancement of Exposure in Social Phobia
Official title: D-Cycloserine Enhancement of Exposure in Social Phobia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Social Anxiety Disorder
Keywords: Social Anxiety Disorder
Cognitive Behavioral Group Therapy
D-cycloserine
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: Boston University
name: Southern Methodist University
name: National Institutes of Health (NIH)
name: National Institute of Mental Health (NIMH)
First posted: 2008-03-12
Enrollment: 169
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Liebowitz Social Anxiety Scale (LSAS)
timeFrame: Week 13
measure: CGI - Clinical Global Impression of Improvement
timeFrame: Week 13
Secondary outcomes:
Other outcomes:
Locations:
city: Boston
country: United States
facility: Center for Anxiety and Traumatic Stress Disorders, Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: mpollack@partners.org
name: Mark H Pollack, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: shofmann@bu.edu
name: Stefan Hofmann
role: PRINCIPAL_INVESTIGATOR
References:
citation: Zalta AK, Dowd S, Rosenfield D, Smits JA, Otto MW, Simon NM, Meuret AE, Marques L, Hofmann SG, Pollack MH. Sleep quality predicts treatment outcome in CBT for social anxiety disorder. Depress Anxiety. 2013 Nov;30(11):1114-20. doi: 10.1002/da.22170. Epub 2013 Aug 26.
citation: Smits JA, Rosenfield D, Otto MW, Marques L, Davis ML, Meuret AE, Simon NM, Pollack MH, Hofmann SG. D-cycloserine enhancement of exposure therapy for social anxiety disorder depends on the success of exposure sessions. J Psychiatr Res. 2013 Oct;47(10):1455-61. doi: 10.1016/j.jpsychires.2013.06.020. Epub 2013 Jul 16.
citation: Hofmann SG, Smits JA, Rosenfield D, Simon N, Otto MW, Meuret AE, Marques L, Fang A, Tart C, Pollack MH. D-Cycloserine as an augmentation strategy with cognitive-behavioral therapy for social anxiety disorder. Am J Psychiatry. 2013 Jul;170(7):751-8. doi: 10.1176/appi.ajp.2013.12070974.