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| Name | Class |
|---|---|
| Rush University Medical Center | OTHER |
| Boston University | OTHER |
| Southern Methodist University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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). |
|
| 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). |
|
| 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). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| D-Cycloserine | Drug | D-cycloserine is a medication thought to be associated with fear extinction. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| 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 |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rush University Medical Center | Chicago | Illinois | 60612 | United States | ||
| Boston University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 37979218 | Derived | 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. | |
| 37399757 | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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). Individuals are administered dcs after the session if exposure is determined successful (SUDS below 40). Individuals are administered the placebo is exposure is determined unsuccessful. The type of pill (i.e. dcs vs. placebo) administered after session is determined after the session. D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction. Placebo: Sugar pill |
| FG001 | 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). D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction. Placebo: Sugar pill |
| FG002 | 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). Placebo: Sugar pill |
| FG003 | 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). D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction. Placebo: Sugar pill |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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). DCS will be administered if the session is deemed a success. D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction. Placebo: Sugar pill |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Intent-to-treat | Posted | Mean | Standard Error | score on a scale | Assessments took place at multiple time points from baseline to 3-month follow-up. The three-month is reported |
|
Data for adverse events was collected at each assessment point over the course of the study (e.g., in-person screening, baseline appointment, sessions 1-5, and the 1-week, 1-month, and 3-month follow-ups).
Participants were asked if they had experienced any injuries or illnesses at the beginning of each study visit.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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). DCS will be administered if the session is deemed a success. D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction. Placebo: Sugar pill |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Serious Adverse Event | Psychiatric disorders | Systematic Assessment | Participant was hospitalized for an aborted suicide attempt during the follow-up phase of the study. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jasper Smits | Institute for Mental Health Research and Department of Psychology, The University of Texas at Austin | 512-475-8095 | smits@utexas.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Nov 2, 2019 | May 26, 2020 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000072861 | Phobia, Social |
| ID | Term |
|---|---|
| D010698 | Phobic Disorders |
| D001008 | Anxiety Disorders |
| D001523 | Mental Disorders |
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| ID | Term |
|---|---|
| D003523 | Cycloserine |
| D015928 | Cognitive Behavioral Therapy |
| ID | Term |
|---|---|
| D007555 | Isoxazoles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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|
| Placebo | Drug | Sugar pill |
|
| 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. |
|
|
| Boston |
| Massachusetts |
| 02215 |
| United States |
| University of Texas at Austin | Austin | Texas | 78712 | United States |
| 34010494 | 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. |
| 32496566 | 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. |
| 31622374 | 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. |
| 26111923 | 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. |
| BG001 |
| 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). D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction. Placebo: Sugar pill |
| BG002 | 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). Placebo: Sugar pill |
| BG003 | 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). D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction. Placebo: Sugar pill |
| BG004 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | Years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Title |
|---|
| Description |
|---|
| OG000 | 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). Individuals are administered dcs after the session if exposure is determined successful (SUDS below 40). Individuals are administered the placebo is exposure is determined unsuccessful. The type of pill (i.e. dcs vs. placebo) administered after session is determined after the session. D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction. Placebo: Sugar pill |
| OG001 | 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). D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction. Placebo: Sugar pill |
| OG002 | 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). Placebo: Sugar pill |
| OG003 | 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). D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction. Placebo: Sugar pill |
|
|
|
| 0 |
| 40 |
| 0 |
| 40 |
| 0 |
| 40 |
| EG001 | 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). D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction. Placebo: Sugar pill | 0 | 38 | 0 | 38 | 0 | 38 |
| EG002 | 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). Placebo: Sugar pill | 0 | 38 | 1 | 38 | 0 | 38 |
| EG003 | 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). D-Cycloserine: D-cycloserine is a medication thought to be associated with fear extinction. Placebo: Sugar pill | 0 | 36 | 0 | 36 | 0 | 36 |
|
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| D023303 |
| Oxazolidinones |
| D010080 | Oxazoles |
| D012694 | Serine |
| D021542 | Amino Acids, Neutral |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
| D001521 | Behavior Therapy |
| D011613 | Psychotherapy |
| D004191 | Behavioral Disciplines and Activities |