Neural Markers of Treatment Mechanisms and Prediction of Treatment Outcomes in Social Anxiety
NCT ID: NCT05683223
Last Updated: 2025-02-19
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.
RECRUITING
NA
240 participants
INTERVENTIONAL
2023-05-26
2027-06-30
Brief Summary
Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.
Data collected from participants who experience anxiety will be compared to a group of 50 participants with little or no social anxiety, who will serve as a comparison group.
Related Clinical Trials
Explore similar clinical trials based on study characteristics and research focus.
Brain Markers of Anxiety Disorders and SSRI/CBT Treatment in Children and Adolescents
NCT01160588
Examining Long-Term Effects and Neural Mediators of Behavioral Treatments for Social Anxiety Disorder
NCT00872820
Computer-Based Treatment for Social Anxiety Disorder
NCT03415022
Investigating How the Brain Processes Different Experiences
NCT06051084
Effect of Behavior Therapy on Responses to Social Stimuli in People With Social Phobia
NCT00380731
Detailed Description
Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.
The investigators will recruit 190 adults with social anxiety disorder (SAD) and 50 adult controls. All adults with SAD will participate in group CBT for SAD. Non-responders will continue on with individual CBT plus the addition of sertraline for another 12 weeks. 50 controls will receive baseline EEG and MRI but will not participate in any clinical interventions. The investigators will also perform neuroimaging (task fMRI, rsfMRI, DWI, structural MRI) and collect EEG before treatment, to compare patient and control groups, and to obtain neuromarkers that predict treatment response.
MRI/EEG Tasks
Activation of Negative Valence System. The RDoC recommends "viewing aversive pictures" as a means to activate the Negative Valence System. The investigators will adapt the paradigm that accounted for 40% of CBT outcome variance in which participants viewed blocks of angry or neutral faces. The investigators chose to use a block (rather than an event-related) design because block designs have stronger measurement power for characterizing individuals. Experimental design. Stimuli will be color faces from the NimStim set with angry or neutral expressions. There will be six 15-second blocks per condition, with six faces per block; each face is presented for 1250 ms, followed by 1250 ms of fixation. The task starts and ends with a fixation block, and each pair of face blocks is separated by one fixation block. Two fixed forms are used to counterbalance condition orders. Participants perform a 1-back task by indicating, via button press, the repetition of a face.
Activation of Positive Valence System. As reviewed in Significance, there is evidence that the reward system is atypical in SAD. To investigate this further, the investigators will adapt a widely used reward processing task that was developed by Delgado and that is recommended by the RDoC for probing the initial response to reward. Experimental design. Participants play a guessing game to try to win money. Each trial begins with presentation of a "mystery card" displaying a "?" (duration: 1.5s). Participants are told that card numbers range from 1 to 9, and they indicate whether they think the mystery card number on a given trial is more or less than 5 by pressing a button. Feedback (1s) is given immediately after and consists of either (a) a reward (a green up arrow and "$1"), (b) a loss (red down arrow with "-$0.50"), or (c) a neutral outcome (the number 5 and a grey double-headed arrow). A 1 s intertrial interval (ITI) separates the trials. Participants complete two runs, each of which includes four blocks of eight trials: two blocks yield mostly rewards (6/8 trials), and two blocks yield mostly losses (6/8 trials). There are also four 15 s fixations, to facilitate deconvolution of fMRI responses.
Activation of Cognitive Control System. Based on encouraging prior findings, the investigators have included a cognitive control task in which pretreatment activation of dorsal anterior cingulate cortex (dACC) predicted response to CBT+SSRI in SAD with 83% accuracy. Experimental design. The task is known as the MSIT. It has four blocks each of two conditions (control and interference). Each block lasts 42 s and consists of 24 trials (1750 ms per trial) in pseudo-randomized order with sets of 3 digits (0, 1, 2, or 3) centrally displayed. One "target" digit differs from the other two (distractors). In the control condition, the distractors are always '0' and the target digit corresponds to its position (i.e., '1' in the leftmost position; '2' in the middle position; and '3' in the rightmost position). Thus, on control trials, the target digit and position are congruent. In the interference condition, the distractors are '1', '2', or '3' and the target digit and position are incongruent (e.g., '1' presented in the rightmost position). Participants indicate if the target digit is '1', '2', or '3' by pressing the response buttons. Ignoring the distractors and the misleading position of the target digit on interference trials requires cognitive control.
Our primary hypotheses are that: (1) The investigators will identify patterns of brain activity that distinguish adults with SAD from adults in the comparison group, and that (2) The investigators will be able to identify patterns of brain activity that predict which adults with SAD will (or will not) respond to treatment.
The primary outcome measure will be treatment response (defined elsewhere in this registration).
Conditions
See the medical conditions and disease areas that this research is targeting or investigating.
Study Design
Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.
NON_RANDOMIZED
PARALLEL
2. Treat 190 SAD patients with CBT for SAD, and treat nonresponders with CBT plus SSRI;
TREATMENT
NONE
Study Groups
Review each arm or cohort in the study, along with the interventions and objectives associated with them.
Responders
The experimental arm involves EEG + MRI before and after exposure therapy for social anxiety disorder.
Group CBT for Social Anxiety Disorder
Initial CBT will consist of 12 weekly, 2.5-hour group sessions. Later sessions (after session 7) become more individualized as the exposure practices are tailored to the individual participant's concerns. Most often, the exposures are completed outside the group environment. Session content includes various cognitive behavioral strategies tailored to SAD, such as psychoeducation, examining and challenging cognitive distortions, and exposure exercises.
Non-Responders
The experimental arm involves EEG + MRI before and after exposure therapy for social anxiety disorder. Non-responders to initial exposure therapy will receive sertraline and additional exposure therapy prior to final EEG and MRI.
Group CBT for Social Anxiety Disorder
Initial CBT will consist of 12 weekly, 2.5-hour group sessions. Later sessions (after session 7) become more individualized as the exposure practices are tailored to the individual participant's concerns. Most often, the exposures are completed outside the group environment. Session content includes various cognitive behavioral strategies tailored to SAD, such as psychoeducation, examining and challenging cognitive distortions, and exposure exercises.
Sertraline
Non-responders will initiate sertraline at baseline (week 0) with 25 mg/day followed by a dose increase to 50 mg/day at week 1, 100 mg at week 4, 150 mg at week 6, and 200 mg at week 8. Upward dose titration may be slowed and the dose decreased if necessary due to side effects, but the clinician will attempt to titrate all symptomatic participants up to 200 mg/day if tolerated by week 8, with the last dose increase allowed at week 10. Participants will be assessed at each visit by the study psychiatrist for purposes of dose titration and monitoring. Symptomatic participants unable to reach 200 mg/day of sertraline due to side effects will be maintained in the trial if they are on at least 50 mg/day by week 8; all symptomatic participants will be titrated to their maximally tolerated dose (\< 200 mg/day sertraline). Any participant unable to tolerate sertraline will be discontinued and referred for clinical treatment.
Individual CBT for Social Anxiety Disorder
Participants who show no or only partial response to the initial group CBT will continue with an individual, tailored form of CBT plus adjunctive SSRI. The format of CBT will include
Controls
Controls will receive baseline EEG and MRI, screening questionnaires and intake interview. They will not participate in therapy but complete weekly symptom measures and a second EEG/MRI session 12 weeks after baseline. Control participants will be compared with social anxiety participants to determine differences in neuro-markers at baseline and over follow-up.
No interventions assigned to this group
Interventions
Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.
Group CBT for Social Anxiety Disorder
Initial CBT will consist of 12 weekly, 2.5-hour group sessions. Later sessions (after session 7) become more individualized as the exposure practices are tailored to the individual participant's concerns. Most often, the exposures are completed outside the group environment. Session content includes various cognitive behavioral strategies tailored to SAD, such as psychoeducation, examining and challenging cognitive distortions, and exposure exercises.
Sertraline
Non-responders will initiate sertraline at baseline (week 0) with 25 mg/day followed by a dose increase to 50 mg/day at week 1, 100 mg at week 4, 150 mg at week 6, and 200 mg at week 8. Upward dose titration may be slowed and the dose decreased if necessary due to side effects, but the clinician will attempt to titrate all symptomatic participants up to 200 mg/day if tolerated by week 8, with the last dose increase allowed at week 10. Participants will be assessed at each visit by the study psychiatrist for purposes of dose titration and monitoring. Symptomatic participants unable to reach 200 mg/day of sertraline due to side effects will be maintained in the trial if they are on at least 50 mg/day by week 8; all symptomatic participants will be titrated to their maximally tolerated dose (\< 200 mg/day sertraline). Any participant unable to tolerate sertraline will be discontinued and referred for clinical treatment.
Individual CBT for Social Anxiety Disorder
Participants who show no or only partial response to the initial group CBT will continue with an individual, tailored form of CBT plus adjunctive SSRI. The format of CBT will include
Other Intervention Names
Discover alternative or legacy names that may be used to describe the listed interventions across different sources.
Eligibility Criteria
Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.
Inclusion Criteria
(1) Liebowitz Social Anxiety Scale (LSAS; Mennin et al., 2002) score \<= 30, does not currently meet criteria for an Axis I psychiatric condition, as defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5; American Psychiatric Association, 2013).
1. Outpatients with a primary psychiatric complaint (designated by the patient as the most important source of current distress) of social anxiety with social interaction fear as defined by an Liebowitz Social Anxiety Scale (LSAS) score \>= 60.
2. Overall clinical severity of at least mild as defined by Clinical Global Impressions Scale (CGI-S; Zaider et al., 2003) of at least 3.
3. Medical history interview and laboratory findings without clinically significant abnormalities.
4. Willingness and ability to participate in the informed consent process and comply with the requirements of the study protocol.
Exclusion Criteria
2. . Patients with significant suicidal ideation Montgomery-Åsberg Depression Rating Scale (10 items, self-report) or who have enacted suicidal behaviors within 6 months prior to intake will be excluded from study participation and referred for appropriate clinical intervention.
3. Patients can be taking a concurrent psychotropic medication (e.g., antidepressants, anxiolytics, beta blockers, sertraline), but the dose must be stabilized for at least 2 weeks prior to initiation of randomized treatment.
4. Significant personality dysfunction likely to interfere with study participation.
5. Serious medical illness, associated treatment, or other instability for which hospitalization may be likely within the next year, or which may alter fMRI or EEG measurements. Participants with a history of serious medical illness or treatments that may alter fMRI measurements may enroll in the study 12 months after the condition has been remitted and ending treatment.
6. Patients with a current or past history of seizures.
7. Pregnant women, lactating women, and women of childbearing potential who may become pregnant.
8. Any concurrent psychotherapy initiated within 3 months of baseline, or ongoing psychotherapy of any duration directed specifically toward treatment of the social anxiety is excluded. Individuals with prior CBT experience or treatments that included cognitive and behavioral skills and exposure procedures (e.g., assertiveness and social skills trainings) will be excluded. General supportive or insight-oriented therapy initiated \> 3 months prior is acceptable.
9. 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).
10. Patients with a history of head trauma causing loss of consciousness, seizure or ongoing cognitive impairment.
11. Contraindications for MRI including metal implants, surgical clips, probability of metal fragments, braces, or claustrophobia.
18 Years
50 Years
ALL
Yes
Sponsors
Meet the organizations funding or collaborating on the study and learn about their roles.
Massachusetts Institute of Technology
OTHER
Mclean Hospital
OTHER
National Institute of Mental Health (NIMH)
NIH
Boston University Charles River Campus
OTHER
Responsible Party
Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.
Anthony J. Rosellini
Associate Professor
Principal Investigators
Learn about the lead researchers overseeing the trial and their institutional affiliations.
John Gabrieli, PhD
Role: PRINCIPAL_INVESTIGATOR
Massachusetts Institute of Technology
Daniel Dillon, PhD
Role: PRINCIPAL_INVESTIGATOR
Mclean Hospital
Anthony Rosellini, PhD
Role: PRINCIPAL_INVESTIGATOR
Boston University Charles River Campus
Locations
Explore where the study is taking place and check the recruitment status at each participating site.
Center for Anxiety and Related Disorders at Boston University
Boston, Massachusetts, United States
Countries
Review the countries where the study has at least one active or historical site.
Central Contacts
Reach out to these primary contacts for questions about participation or study logistics.
Facility Contacts
Find local site contact details for specific facilities participating in the trial.
References
Explore related publications, articles, or registry entries linked to this study.
Bush G, Shin LM, Holmes J, Rosen BR, Vogt BA. The Multi-Source Interference Task: validation study with fMRI in individual subjects. Mol Psychiatry. 2003 Jan;8(1):60-70. doi: 10.1038/sj.mp.4001217.
Delgado MR, Nystrom LE, Fissell C, Noll DC, Fiez JA. Tracking the hemodynamic responses to reward and punishment in the striatum. J Neurophysiol. 2000 Dec;84(6):3072-7. doi: 10.1152/jn.2000.84.6.3072.
Tottenham N, Tanaka JW, Leon AC, McCarry T, Nurse M, Hare TA, Marcus DJ, Westerlund A, Casey BJ, Nelson C. The NimStim set of facial expressions: judgments from untrained research participants. Psychiatry Res. 2009 Aug 15;168(3):242-9. doi: 10.1016/j.psychres.2008.05.006. Epub 2009 Jun 28.
Other Identifiers
More Related Trials
Additional clinical trials that may be relevant based on similarity analysis.