Effect of D-cycloserine Plus Cognitive Behavioral Therapy on People With Social Phobia

D-cycloserine Enhancement of Exposure in Social Phobia

This study will assess the effectiveness of D-cycloserine combined with cognitive-behavior therapy in treating people with social anxiety disorder.

Study Overview

• Status: Completed
• Conditions: Social Anxiety Disorder
• Intervention / Treatment: Drug: D-cycloserine; Behavioral: Cognitive behavioral therapy (CBT); Drug: Placebo

Detailed Description

Social anxiety disorder (SAD) is among the most common psychiatric conditions and is associated with significant distress and dysfunction in social situations. Although treatment with cognitive-behavior therapy (CBT) is known to help remedy SAD, many patients do not respond to this treatment and most do not reach full recovery. In CBT, patients undergo repeated and prolonged exposure practices to feared social situations to learn better ways to deal with anxiety in these settings. Exposure therapy is based on animal models of extinction of conditioned fears, and recent animal research has identified some of the core pathways and neurotransmitters involved in fear extinction. D-cycloserine (DCS) is a drug that appears to facilitate learning and the process of extinction of conditioned fear in both animals and humans. This study will assess the effectiveness of DCS combined with CBT in treating people with SAD.

Participants in this double-blind study will be randomly assigned to an active or control group. All participants will attend 18 study visits at the Center for Anxiety and Related Disorders over a 9-month period. There will be 12 CBT sessions of 90 minutes each and 6 assessment visits. The CBT sessions will help participants to become more comfortable with social situations. During 5 of the CBT sessions, participants will receive a pill containing either DCS or sugar (placebo). Assessment visits will include interviews, self-report questionnaires, and laboratory tests. These visits will occur at Weeks 1, 7, and 12 during treatment and at Months 3, 6, and 9 post-treatment.

• Study Type: Interventional
• Enrollment (Actual): 169
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Boston University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Meets DSM-IV criteria for generalized social anxiety disorder (GSAD)
• Total score of greater than or equal to 60 on the LSAS
• Physical examination, electrocardiogram, and laboratory findings without clinically significant abnormalities

Exclusion Criteria:

• Lifetime history of bipolar disorder, schizophrenia, psychosis, delusional disorders, or obsessive-compulsive disorder
• Eating disorder within the 6 months prior to study entry
• History of organic brain syndrome, mental retardation, or other cognitive dysfunction
• Substance or alcohol abuse or dependence (other than nicotine) within the 6 months prior to study entry or inability to refrain from alcohol use during the acute period of study participation
• Post-traumatic stress disorder within 6 months prior to study entry; entry of patients with other mood or anxiety disorders will be permitted if the social anxiety disorder is judged to be the predominant disorder
• Suicidal thoughts
• Taking concurrent psychotropic medication (e.g., antidepressants, anxiolytics, beta blockers) within 2 weeks of study entry
• Significant personality dysfunction
• Serious medical illness or instability for which hospitalization may be likely within the next year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: CBT plus d-cycloserine; Participants will receive cognitive behavioral therapy plus D-cycloserine	Drug: D-cycloserine; 50 mg; Other Names: Seromycin; Behavioral: Cognitive behavioral therapy (CBT); CBT sessions aim to help participants become more comfortable with social situations.
Placebo Comparator: CBT plus placebo; Participants will receive cognitive behavioral therapy plus pill placebo	Behavioral: Cognitive behavioral therapy (CBT); CBT sessions aim to help participants become more comfortable with social situations.; Drug: Placebo; Same dosage as active pill; Other Names: Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Social Phobic Disorders Severity and Change Form	Social Phobic Disorders Severity and Change Form (SPD-SC Form; Liebowitz et al., 1992) is an expansion and adaptation of the Clinical Global Impression Scale (CGI) by Guy (1976) to SAD. Similar to the original CGI scale, the SPD-SC Form is rated by an independent evaluator on a 7-point scale to indicate severity (1=normal/not ill; 2 = minimally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most severely ill) and improvement (1=very much improved; 2=much improved; . 3=minimally improved' 4 = no change; 5=nimimal deterioration; 6=severe deterioration; 7=very severe deterioration). The primary outcome measure is units of a scale ranging from 1 (very much improved) to 7 (very severe deterioration).	Measured at Months 3 (immediately after treatment)
Liebowitz Social Anxiety Scale (LSAS)	The Liebowitz Social Anxiety Scale (LSAS; Liebowitz, 1987) is a 24-item scale that provides separate scores for fear and avoidance in social and performance situations; it is widely used in treatment studies of SAD. Total scores range from 0 (no anxiety) to 144 (maximum).	Measured at Months 3

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Social Phobia and Anxiety Inventory	The Social Phobia and Anxiety Inventory (SPAI; Turner, Beidel, Dancu, and Stanley, 1989) is a 45-item self-report measure on the frequency (0 = Never, 1 = Very Infrequent, 2 = Infrequent, 3 = Sometimes, 4 = Frequent, 5 = Very Frequent, 6 = Always) of one's experiences. The inventory includes 32 items assessing somatic, cognitive, and behavioral symptoms of social anxiety and 13 items assessing agoraphobia. The final score is calculated by subtracting the agoraphobia subscale total (max = 78; min = 0) from the social phobia subscale total (max = 192; min = 0). Thus, the final total scores range from 0-114, where higher final scores indicate higher social anxiety.	Measured at Months 3, 6, and 9 post-treatment
Quality of Life Enjoyment and Satisfaction Questionnaire	The Quality of Life Enjoyment and Satisfaction Questionnaire (Endicott et al., 1993) is a 16-item self-report measure that rates aspects of quality of life, including physical health, mood, activities of daily living, and overall life satisfaction. Responses are scored on a 5 point scale. The maximum score is 70 (high satisfaction) and the minimum is 14 (low satisfaction); scores are generally expressed as a percentage of maximum total score (0-100).	Measured at Months 3, 6, and 9 post-treatment
Liebowitz Self-Rated Disability Scale	Liebowitz Self-Rated Disability Scale (Schneier et al., 1994) is an 11-item scale assessing impairment specific to social anxiety. Current (past 2 weeks) and most severe lifetime impairment due to social anxiety disorder are rated on a 0-3 scale of degree of limitation (0=problem does not limit me at all; 3=problem limits me severely). The maximum score is 44 (severe impairment) and the minimum is 0 (no impairment).	Measured at Months 3, 6, and 9 post-treatment
Range of Impaired Functioning Tool	The Range of Impaired Functioning Tool (LIFE-RIFT, Leon et al., 2000) is a clinician rated scale assessing functioning in four domains: work, interpersonal relationships, recreation, and global satisfaction. Each domain is scored 0-5 (0=not applicable, 1=no impairment, 2=slight impairment, 3=mild impairment, 4=moderate impairment, 5=severe impairment). The total score is the sum of each domain's score, with a maximum score of 20 (severe impairment) and a minimum score of 4 (no impairment).	Measured at Months 3, 6, and 9 post-treatment

Collaborators and Investigators

• Sponsor: Boston University Charles River Campus
• Collaborators: National Institute of Mental Health (NIMH)
• Investigators: Principal Investigator: Stefan G. Hofmann, PhD, Boston University; Principal Investigator: Mark H. Pollack, MD, Massachusetts General Hospital; Study Director: Jasper A. Smits, PhD, Southern Methodist University

Publications and helpful links

General Publications

• Hofmann SG, Pollack MH, Otto MW. Augmentation treatment of psychotherapy for anxiety disorders with D-cycloserine. CNS Drug Rev. 2006 Fall-Winter;12(3-4):208-17. doi: 10.1111/j.1527-3458.2006.00208.x.
• Otto MW, Basden SL, Leyro TM, McHugh RK, Hofmann SG. Clinical perspectives on the combination of D-cycloserine and cognitive-behavioral therapy for the treatment of anxiety disorders. CNS Spectr. 2007 Jan;12(1):51-6, 59-61. doi: 10.1017/s1092852900020526.
• Hofmann SG, Meuret AE, Smits JA, Simon NM, Pollack MH, Eisenmenger K, Shiekh M, Otto MW. Augmentation of exposure therapy with D-cycloserine for social anxiety disorder. Arch Gen Psychiatry. 2006 Mar;63(3):298-304. doi: 10.1001/archpsyc.63.3.298.

Study record dates

Study Major Dates

• Study Start: December 1, 2007
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: August 10, 2007
• First Submitted That Met QC Criteria: August 10, 2007
• First Posted (Estimate): August 14, 2007

Study Record Updates

• Last Update Posted (Actual): February 26, 2019
• Last Update Submitted That Met QC Criteria: February 5, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Generalized subtype
• Additional Relevant MeSH Terms: Mental Disorders; Phobic Disorders; Anxiety Disorders; Phobia, Social; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antimetabolites; Anti-Bacterial Agents; Antitubercular Agents; Antibiotics, Antitubercular; Anti-Infective Agents, Urinary; Renal Agents; Cycloserine
• Other Study ID Numbers: R01MH078308 (U.S. NIH Grant/Contract); R01MH075889 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No