Dose Timing of D-Cycloserine to Augment CBT for Social Anxiety Disorder

NCT02066792 | Completed Early Phase 1 Results DMC

• 1 other identifier: R34MH099318
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 3

Brief Summary

The purpose of this study is to examine the efficacy of 50 mg of d-cycloserine in comparison to placebo (a pill containing no medication) for improving the effectiveness of cognitive-behavioral therapy (CBT) in reducing symptoms associated with social anxiety disorder. In addition, the study will examine whether the effectiveness of d-cycloserine depends on the timing of the pill administration (i.e., 1- hour before the session or immediately after the session) as well as the success of the CBT therapy sessions. The investigators hypothesize that the tailored post-session DCS administration condition will outperform the other conditions (pre-session DCS, placebo, and non-tailored post-session DCS). This will be evidenced by short- and long-term improvements in social anxiety severity.

Conditions

Social Anxiety Disorder

Keywords

Social Phobia

Outcome Measures

Primary Outcomes (1)

• Social Anxiety Symptom Severity

  The main outcome was a composite Z-score from the Liebowitz Social Anxiety Scale (LSAS) and the Social Phobic Disorders Severity and Change Form (SPD-SC Form). "The Composite Z-score of the LSAS and SPD-SC Form indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean of a reference population. Negative numbers indicate values lower symptom severity and positive numbers indicate higher symptom severity. The LSAS is a 24-item scale that measures fear and avoidance in social and performance situations within the last week, using 0 (no fear/never avoids) to 3 (severe fear/usually avoids) scale. LSAS scores range from 0-144 with higher scores indicated worse outcomes. The SPD-S is the Clinical Global Impression Scale27 adapted for SAD, which instructs evaluators to use a 7-point scale (1=normal, not at all ill; 7=among the most extremely ill patients) to index the severity of social anxiety.

  Assessments took place at multiple time points from baseline to 3-month follow-up. The three-month is reported

Study Arms (4)

Tailored Post-Session DCS

EXPERIMENTAL

Individuals in this condition will receive 5 weeks of CBT for social anxiety disorder and two pills (i.e. one placebo before and one dcs/placebo after the session). The type of pill (i.e. dcs vs. placebo) will be determined after the session.

Drug: D-Cycloserine; Drug: Placebo; Behavioral: Cognitive Behavioral Therapy

Pre-Session DCS

ACTIVE COMPARATOR

Individuals in this condition will receive 5 weeks of CBT for social anxiety disorder and two pills (i.e. one dcs before and one placebo after the session).

Drug: D-Cycloserine; Drug: Placebo; Behavioral: Cognitive Behavioral Therapy

Placebo

PLACEBO COMPARATOR

Individuals in this condition will receive 5 weeks of CBT for social anxiety disorder and two pills (i.e. one placebo before and one placebo after the session).

Drug: Placebo; Behavioral: Cognitive Behavioral Therapy

Non-Tailored Post-Session DCS

ACTIVE COMPARATOR

Individuals in this condition will receive 5 weeks of CBT for social anxiety disorder and two pills (i.e. one placebo before and one dcs after the session).

Drug: D-Cycloserine; Drug: Placebo; Behavioral: Cognitive Behavioral Therapy

Interventions

D-Cycloserine DRUG

D-cycloserine is a medication thought to be associated with fear extinction.

Also known as: D-cycloserine, DCS

Non-Tailored Post-Session DCS; Pre-Session DCS; Tailored Post-Session DCS

Placebo DRUG

Sugar pill

Non-Tailored Post-Session DCS; Placebo; Pre-Session DCS; Tailored Post-Session DCS

Cognitive Behavioral Therapy BEHAVIORAL

This will be a 5-session version of a group CBT protocol with 4-6 patients and 2 therapists per group emphasizing repeated exposure practices. Session 1 involves an introduction and orientation to the CBT model. Sessions 2-5 emphasize repeated exposure tasks, which consist of role-play activities to confront fearful situations in a group setting while disputing cognitive distortions (coupled with the fading of safety behaviors). At the conclusion of each exposure session, patients will be encouraged to continue to apply home-practice strategies (such as giving speeches in front of a mirror). Continued practice of the interventions will be considered part of treatment, and patients will be asked to refrain from alternative treatment for four weeks following completion of the last treatment session.

Also known as: CBT

Non-Tailored Post-Session DCS; Placebo; Pre-Session DCS; Tailored Post-Session DCS

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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 social anxiety disorder as defined by DSM-5 criteria.
• A total score \> 60 on the LSAS.
• Physical examination and laboratory findings without clinically significant abnormalities.
• Willingness and ability to participate in the informed consent process and comply with the requirements of the study protocol.

You may not qualify if:

• 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.
• PTSD within the past 6 months. Entry of patients with other mood or anxiety disorders will be permitted if the SAD 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.
• Patients must be off concurrent psychotropic medication (e.g., antidepressants, anxiolytics, beta blockers) for at least 2 weeks prior to initiation of randomized treatment.
• Significant personality dysfunction likely to interfere with study participation.
• Serious medical illness or instability for which hospitalization may be likely within the next year.
• Patients with a current or past history of seizures.
• 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).
• Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of the SAD is excluded. Prohibited psychotherapy includes CBT or psychodynamic therapy focusing on exploring specific, dynamic causes of the phobic symptomatology and providing management skills. General supportive therapy initiated \> 3 months prior is acceptable.
• 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).
• Patients with a history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment. Current use of isoniazid or ethionamide compounds
• Insufficient command of the English language

Sponsors & Collaborators

• Rush University Medical Center: collaborator
• Boston University: collaborator
• Southern Methodist University: collaborator
• Jasper A. Smits: lead

Study Sites (3)

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Boston University

Boston, Massachusetts, 02215, United States

Location

University of Texas at Austin

Austin, Texas, 78712, United States

Location

Related Publications (6)

• Taylor CT, Rosenfield D, Dowd SM, Dutcher CD, Hofmann SG, Otto MW, Pollack MH, Smits JAJ. What good are positive emotions for treatment? A replication test of whether trait positive emotionality predicts response to exposure therapy for social anxiety disorder. Behav Res Ther. 2023 Dec;171:104436. doi: 10.1016/j.brat.2023.104436. Epub 2023 Nov 11.

  PMID: 37979218 DERIVED

• Lubin RE, Fitzgerald HE, Rosenfield D, Carpenter JK, Papini S, Dutcher CD, Dowd SM, Hofmann SG, Pollack MH, Smits JAJ, Otto MW. Using pre-treatment de novo threat conditioning outcomes to predict treatment response to DCS augmentation of exposure-based CBT. J Psychiatr Res. 2023 Aug;164:357-363. doi: 10.1016/j.jpsychires.2023.06.008. Epub 2023 Jun 19.

  PMID: 37399757 DERIVED

• Dutcher CD, Dowd SM, Zalta AK, Taylor DJ, Rosenfield D, Perrone A, Otto MW, Pollack MH, Hofmann SG, Smits JAJ. Sleep quality and outcome of exposure therapy in adults with social anxiety disorder. Depress Anxiety. 2021 Nov;38(11):1182-1190. doi: 10.1002/da.23167. Epub 2021 May 19.

  PMID: 34010494 DERIVED

• Smits JAJ, Pollack MH, Rosenfield D, Otto MW, Dowd S, Carpenter J, Dutcher CD, Lewis EM, Witcraft SM, Papini S, Curtiss J, Andrews L, Kind S, Conroy K, Hofmann SG. Dose Timing of D-Cycloserine to Augment Exposure Therapy for Social Anxiety Disorder: A Randomized Clinical Trial. JAMA Netw Open. 2020 Jun 1;3(6):e206777. doi: 10.1001/jamanetworkopen.2020.6777.

  PMID: 32496566 DERIVED

• Hofmann SG, Papini S, Carpenter JK, Otto MW, Rosenfield D, Dutcher CD, Dowd S, Lewis M, Witcraft S, Pollack MH, Smits JAJ. Effect of d-cycloserine on fear extinction training in adults with social anxiety disorder. PLoS One. 2019 Oct 17;14(10):e0223729. doi: 10.1371/journal.pone.0223729. eCollection 2019.

  PMID: 31622374 DERIVED

• Hofmann SG, Carpenter JK, Otto MW, Rosenfield D, Smits JA, Pollack MH. Dose timing of D-cycloserine to augment cognitive behavioral therapy for social anxiety: Study design and rationale. Contemp Clin Trials. 2015 Jul;43:223-30. doi: 10.1016/j.cct.2015.06.015. Epub 2015 Jun 23.

  PMID: 26111923 DERIVED

MeSH Terms

Conditions

Phobia, Social

Interventions

Cycloserine; Cognitive Behavioral Therapy

Condition Hierarchy (Ancestors)

Phobic Disorders; Anxiety Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Isoxazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Oxazolidinones; Oxazoles; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Behavior Therapy; Psychotherapy; Behavioral Disciplines and Activities

Results Point of Contact

• Title: Dr. Jasper Smits
• Organization: Institute for Mental Health Research and Department of Psychology, The University of Texas at Austin

smits@utexas.edu

512-475-8095

Study Officials

• Mark Pollack, M.D.

  Rush University Medical Center

  PRINCIPAL INVESTIGATOR

• Stefan Hofmann, Ph.D.

  Boston University

  PRINCIPAL INVESTIGATOR

• Jasper A Smits, Ph.D.

  University of Texas at Austin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: February 17, 2014
• First Posted: February 20, 2014
• Study Start: April 1, 2014
• Primary Completion: July 1, 2018
• Study Completion: July 1, 2018
• Last Updated: June 15, 2026
• Results First Posted: June 9, 2020

Record last verified: 2020-05

Locations

US (3)