Clinical trial NCT04879641: Optimizing Cognitive-behavioral Therapy for Social Anxiety Disorder Using the Factorial Design
Official title: Optimizing Cognitive-behavioral Therapy for Social Anxiety Disorder Using the Factorial Design: What Works Best and How Does it Work (OPTIMIZE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Social Anxiety Disorder (Social Phobia)
Lead sponsor: University of Bern
Sponsor class: OTHER
Collaborators: name: University of Luebeck
First posted: 2021-05-10
Enrollment: 464
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: The study is a single-center, factorial trial with four experimental factors (treatment components, i.e., psychoeducation, cognitive restructuring, attention training, and exposure) each evaluated at two levels (presence vs. absence) resulting in 16 treatment conditions.
Primary purpose: TREATMENT

Brief summary: Social Anxiety Disorder (SAD) is characterized by a marked fear of negative evaluation in social situations. It is the third most common psychiatric disorder and highly disabling (American Psychiatric Association, 2000). Although effective treatments such as cognitive-behavioral therapy (CBT) are available, most individuals suffering from SAD do not seek and eventually find help, and even in the best available treatments, remission rates are below 50%. The overall aim of the project is to better understand and improve the efficacy of Internet-based CBT (ICBT) that has shown to be efficacious in many trials and that provide broad and low-threshold access to empirically supported treatments. Specifically the objectives of the study are:

1. to investigate the active ingredients of ICBT for SAD by testing the main effects and interactions for the four main treatment components (i.e., psychoeducation, cognitive restructuring, attention training, and exposure);
2. to investigate the effects of each treatment component on hypothesized change mechanisms, and to explore whether and which change mechanisms mediate the effect of the treatment components on symptom reduction.
3. to investigate whether the specific mechanisms mediate the effect of the treatment components on primary and secondary outcomes.

Detailed description: Social Anxiety Disorder (SAD) is characterized by a marked fear of negative evaluation in social situations. It is the third most common psychiatric disorder and highly disabling. Although effective treatments such as cognitive-behavioral therapy (CBT) are available, most individuals suffering from SAD do not seek and eventually find help, and even in the best available treatments, remission rates are below 50%. The overall aim of the project is to improve the efficacy of Internet-based CBT (ICBT) that has shown to be efficacious in many trials and that provide broad and low-threshold access to empirically supported treatments. Specifically, the objectives of the study are:

1. to investigate the active ingredients of ICBT for SAD by testing the main effects and interactions for the four main treatment components (i.e., psychoeducation, cognitive restructuring, attention training, and exposure);
2. to investigate the effects of each treatment component on hypothesized change mechanisms (change of the knowledge of SAD, change on negative social cognitions, changes on self-focused attention, changes on social avoidance and use of safety behaviors), and to explore whether and which change mechanisms mediate the effect of the treatment components on symptom reduction.
3. to investigate whether the specific mechanisms mediate the effect of the treatment components on primary and secondary outcomes.

The study is a single-center, factorial trial with four experimental factors (treatment components, i.e., psychoeducation, cognitive restructuring, attention training, and exposure) each evaluated at two levels (presence vs. absence) resulting in 16 conditions.

Recruitment: Participants will be recruited using reports in newspapers, through internet forums, social media (e.g., Facebook), and via our website (https://www.online-therapy.ch/) in German-speaking countries.

Sampling: After checking the inclusion criteria, participants will be randomized with equal probability to one of the 16 conditions. The random allocation will be unknown to the investigators. In order to keep the sample sizes of the 16 conditions similar, the allocation list will be made using randomly permuted blocks. A total of 464 participants with a Diagnostic and Statistical Manual of Mental Disorders diagnosis of SAD will be included, with 29 patients being assigned to each of the 16 conditions.

Assessment procedures: The primary outcome measure is change in symptoms of SAD at post-treatment, i.e., after 8 weeks. Secondary outcomes include sustaining change at follow up (6 months after baseline), changes in depressive symptoms, changes in general anxiety symptoms, changes in quality of life, adherence to treatment, treatment satisfaction, negative effects and changes of diagnosis of SAD. Furthermore, the hypothesized change mechanisms (change of the knowledge of SAD, change on negative social cognitions, changes in self-focused attention, changes in social avoidance and use of safety behaviors) will be assessed. Self-report measures are taken at pre-treatment (baseline), after 4 weeks (mid-treatment), after 8 weeks (post-treatment), and at 6 months after randomization (follow-up). Besides the self-report measures, a diagnostic interview will be conducted by phone at pre-treatment, eight weeks (posttreatment), and six months (follow-up). The structured M.I.N.I. Interview will be used. The interviews will be administered by advanced Master students in clinical psychology and psychotherapy supervised by the study team. Interrater reliability will be assessed on a subset of the cases.

Treatment: The internet-based self-help program ("Shyne", https://selfhelp1.psy.unibe.ch/shyne/) is based on the well-established cognitive-behavioral treatment of social anxiety by Clark and Wells and has been proven efficacious in previous studies. Shyne is accessed through a secure website, with each participant having a password-protected account. It consists of the following four treatment components: (1) psychoeducation (knowledge about SAD and its treatment); (2) cognitive restructuring (challenging dysfunctional social cognitions); (3) attention training (decrease of self-focused attention); and (4) exposure (decrease of avoidance of feared situations and safety behaviors). These treatment components will be offered in 16 different combinations.

Data analysis: Primary analyses will be conducted on the Intention-To-Treat (ITT) sample (i.e., all randomized participants). The analyses are carried out on the basis of the intention-to-treat (ITT) approach using linear mixed models. In addition, but only secondary, completers analysis will be carried out. In order to test for main and interaction effects of treatment components on outcomes and change mechanisms across the time points of assessment, linear mixed models Analysis of Variance (ANOVA) or latent growth curve modelling will be used. Main effects and interactions will be based on aggregates across experimental conditions. Sensitivity analyses will explore the impact of the imputation of missing values. For binary outcome data (i.e., SAD diagnosis), a logistic regression model will be used. Furthermore, mediation analyses will be used to determine whether the hypothesized change mechanisms mediate the effect of the treatment components on primary and secondary outcomes. The mediation will be tested using an approach that allows multiple mediators in one model. In addition, potential moderation of the treatment components by various measured variables such as comorbid disorder, medication, the severity of SAD, age and sex will be investigated. Reporting will follow CONSORT E-Health standards.

Eligibility criteria: Inclusion Criteria:

* 1. read the study information and sign informed consent;
* 2. are 18 years or older;
* 3. have access to the Internet, to a smartphone, PC or tablet;
* 4. have sufficient knowledge of German;
* 5. exceed predefined cut-off scores on one of the social anxiety measures (22 points on the Social Phobia Scale or 33 points on the Social Interaction Anxiety Scale; SPS \& SIAS);
* 6. fulfil the diagnostic criteria of SAD according to the diagnostic telephone interview (the presence of other disorders does not result in exclusion if SAD is the primary diagnosis)
* 7. in the case of taking psychiatric medication, the treatment is stabilized (over one month)

Exclusion Criteria:

* 1. they score 2 or higher on the suicide item of the PHQ-9 (Spitzer, 1999) or with active suicidal plans in the diagnostic telephone interview.
* 2. they have other comorbid psychiatric conditions that might be the main focus of clinical attention (e.g., psychotic symptoms, bipolar disorder, or other severe disorder)
* 3. they undergo another psychological treatment at the beginning of the study.

Primary outcomes:
measure: Change on social anxiety symptoms at post-treatment
timeFrame: Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline)
Secondary outcomes:
measure: Change on social anxiety symptoms at follow-up
timeFrame: Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline)
measure: Change on the severity of depressive symptoms
timeFrame: Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline)
measure: Change on the severity of general anxiety symptoms
timeFrame: Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline)
measure: Change on quality of life
timeFrame: Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline)
measure: Level of satisfaction with the treatment
timeFrame: Post-treatment (8 weeks after baseline)
measure: Negative effects of the treatment
timeFrame: Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline)
measure: Change on the diagnosis of social anxiety disorder
timeFrame: Baseline, Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline)
Other outcomes:
measure: Change on the knowledge of social anxiety disorder
timeFrame: Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline)
measure: Change on negative social cognitions
timeFrame: Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline)
measure: Change on self-focused attention (or self-consciousness)
timeFrame: Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline)
measure: Change on social avoidance and intensity of distress facing social situations
timeFrame: Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline)
measure: Change on the use of safety behaviors in social situations
timeFrame: Baseline, Mid-treatment (4 weeks after baseline), Post-treatment (8 weeks after baseline), Follow-up (6 months after baseline)
Locations:
city: Bern
country: Switzerland
facility: Clinical Psychology and Psychotherapy Department, University of Bern
Study officials:
affiliation: University Bern, Clinical Psychology and Psychotherapy Department
name: Thomas T Berger, Prof.
role: PRINCIPAL_INVESTIGATOR
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