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

NCT ID: NCT02066792

Last Updated: 2020-06-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 152 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2018-07-01

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Tailored Post-Session DCS

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.

Group Type: EXPERIMENTAL

D-Cycloserine

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Sugar pill

Cognitive Behavioral Therapy

Intervention Type: 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.

Pre-Session DCS

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).

Group Type: ACTIVE_COMPARATOR

D-Cycloserine

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Sugar pill

Cognitive Behavioral Therapy

Intervention Type: 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.

Placebo

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).

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Sugar pill

Cognitive Behavioral Therapy

Intervention Type: 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.

Non-Tailored Post-Session DCS

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).

Group Type: ACTIVE_COMPARATOR

D-Cycloserine

Intervention Type: DRUG

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

Placebo

Intervention Type: DRUG

Sugar pill

Cognitive Behavioral Therapy

Intervention Type: 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.

Interventions

D-Cycloserine

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

Intervention Type: DRUG

Placebo

Sugar pill

Intervention Type: DRUG

Cognitive Behavioral Therapy

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.

Intervention Type: BEHAVIORAL

Other Intervention Names

D-cycloserine, DCS; CBT

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Rush University Medical Center

OTHER

Sponsor Role: collaborator

Boston University

OTHER

Sponsor Role: collaborator

Southern Methodist University

OTHER

Sponsor Role: collaborator

University of Texas at Austin

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mark Pollack, M.D.

Role: PRINCIPAL_INVESTIGATOR

Rush University Medical Center

Stefan Hofmann, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Boston University

Jasper A Smits, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Texas at Austin

Locations

Rush University Medical Center

Chicago, Illinois, United States

Boston University

Boston, Massachusetts, United States

University of Texas at Austin

Austin, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 37979218 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37399757 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34010494 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32496566 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31622374 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26111923 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

R34MH099318

Identifier Type: NIH

Identifier Source: org_study_id

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