Social AnxietyUNFEARNCT03465137
Using the Neuroscience of Fear Extinction for Anxiety Reduction
A study testing Coordinated Anxiety Learning and Management (CALM) in people with Social Anxiety, run by Stanford University at 1 site in United States.
Trial summary
Social anxiety disorder affects as many as 12% of Americans, resulting in significant distress and disability. Although exposure therapy is one of the best treatments available, as many as 25% of patients do not respond and we do not know why. Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Social Anxiety
- What is being tested?
- Coordinated Anxiety Learning and Management (CALM)
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- 14 Jan 2018to 30 Sep 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- age 18-50
- primary diagnosis of social anxiety disorder
- fluent spoken and written English
- able to provide informed consent.
Who cannot join
- history of mania or psychosis
- current moderate or severe substance use disorder
- current major depression greater than moderate severity
- high risk for suicide
- prior traumatic brain injury with loss of consciousness >5 minutes
- general medical condition or impediment to vision, hearing, or motor function likely to interfere with assessments
Show all 11Show fewer
- prior exposure therapy (>2 sessions)
- current use of psychotropic medication
- current psychotherapy other than couples counseling
- post-menopausal status
- pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University Department of Psychiatry & Behavioral Sciences
Palo Alto, California, 94304
About this study
Official title: Developing a Mechanistic Neurobiological Model of Exposure Therapy Response Based on Fear Extinction Theory
Social anxiety disorder affects as many as 12% of Americans, resulting in significant distress and disability. Although exposure therapy is one of the best treatments available, as many as 25% of patients do not respond and we do not know why. Extinction learning is thought to be the mechanism of exposure therapy, and the neuroscience of extinction learning has advanced significantly since exposure therapy was developed; however, there has been little application towards improved clinical outcomes.
This project aims to improve exposure therapy response for patients with social anxiety disorder by directly linking exposure therapy response to the neurobiology of extinction learning. It also aims to increase our scientific understanding of how brain circuits work to support extinction learning. To do this, 80 adults with social anxiety disorder will randomly be assigned to either receive exposure therapy right away, or to wait before therapy. Participants will all complete a functional magnetic resonance imaging scan to assess extinction learning before the therapy.
Read the detailed description
The best available treatment for social anxiety disorder is exposure therapy; however, 25% of socially anxious patients do not respond to an adequate course of exposure therapy and it is unclear why. Prior attempts to identify non-responders using clinical and demographic features have been largely unsuccessful, highlighting the need to examine constructs that are more closely tied to the mechanism of treatment (i.e., extinction learning and recall) and the organ of dysfunction (i.e., the brain). The neurobiology of extinction learning and recall is well understood from decades of animal and pre-clinical laboratory work, which has highlighted the importance of the amygdala, dorsal anterior cingulate cortex (dACC), and ventromedial prefrontal cortex (vmPFC). However, this knowledge has not been leveraged to improve exposure therapy response, despite the assumption that response relies on extinction learning and its successful recall.
Thus, a critical long-term goal is to improve exposure therapy response by tailoring therapy based on the neurobiological profile of each patient. This project addresses that goal by directly linking neurobiological profiles of extinction learning and recall with clinical symptoms and therapy response. A major objective of this project is therefore to build a mechanistic predictive model of exposure therapy response based on the neurobiology of extinction learning and recall.
To accomplish this goal, the investigators will recruit 80 adults with social anxiety disorder who will be randomized to 10 sessions of exposure-focused therapy or waitlist. The primary clinical outcome measure will be the Liebowitz Social Anxiety Scale (LSAS), a validated and widely used measure that assesses anxiety and avoidance symptoms. Pre-therapy, participants will also undergo an experimental protocol for extinction learning and recall. Participants will first view a neutral abstract image repeatedly paired with a loud aversive noise, and another image that is never paired (fear acquisition phase). Following this, participants will view the same images without aversive consequences (extinction learning phase). Better extinction learning will be defined as greater reductions in skin conductance within the extinction learning phase. Brain activation during extinction learning will be assessed in the amygdala, dACC, and vmPFC. Finally, participants will view the same images without aversive consequences one week later (extinction recall phase). Better extinction recall will be defined as less skin conductance during extinction recall relative to fear acquisition. The central hypothesis is that greater activation in the vmPFC during extinction learning will predict both extinction recall and therapy response over and above symptom severity.
- Conditions
- Social Anxiety
- Being tested
- Coordinated Anxiety Learning and Management (CALM)
- Keywords
- Exposure therapy, Behavioral therapy, fMRI, Extinction learning, Social anxiety
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Coordinated Anxiety Learning and Management (CALM)Behavioural
Exposure-focused cognitive behavioral therapy
| Study group | Role | What they receive |
|---|---|---|
| Immediate therapy | Experimental | Participants randomized to the immediate therapy arm will receive a weekly individual psychotherapy intervention called Coordinated Anxiety Learning and Management (CALM). The CALM program is an evidence based, exposure-focused therapy (http://calmtoolsforliving.org). Its computer-assisted format guides the therapist through psychoeducation, an introduction to cognitive restructuring, in-session and at-home exposures, and relapse prevention. Therapy will be delivered in 10 weekly 50-minute sessions within a 12 week period. Receives: Behavioral: Coordinated Anxiety Learning and Management (CALM) |
| Waitlist | No intervention | Participants randomized to the waitlist arm will receive no intervention for 12 weeks. After this 12 week period they will receive a the same weekly individual psychotherapy intervention as the immediate therapy group: Coordinated Anxiety Learning and Management (CALM). The CALM program is an evidence based, exposure-focused therapy (http://calmtoolsforliving.org). Its computer-assisted format guides the therapist through psychoeducation, an introduction to cognitive restructuring, in-session and at-home exposures, and relapse prevention. Therapy will be delivered in 10 weekly 50-minute sessions within a 12 week period. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liebowitz Social Anxiety Scale (LSAS)
A validated, widely-used measure of social anxiety severity, with anxiety and avoidance subscales. Subscales range from 0 to 72, with higher scores indicating greater anxiety and avoidance symptoms. A total score is computed by summing the two subscales (range: 0 to 144, higher scores indicate greater social anxiety severity).
Measured: 12 weeks
Secondary outcomes (3)
Patient Health Questionnaire (PHQ-9)
A validated and widely-used measure of depression symptom severity, ranging from 0 to 27, with higher scores indicating greater depression severity.
Measured: 12 weeks
Brief Fear of Negative Evaluation (BFNE)
A validated measure of fear of negative evaluation, a key concept in social anxiety disorder, ranging from 0 to 32, with higher scores indicating greater fear of negative evaluation.
Measured: 12 weeks
World Health Organization Quality of Life scale (WHO-QOL)
A validated measure of quality of life, which has subscales for physical health, psychological health, social relationships, and environment. Subscales scores are each transformed into a 0-100 range, with higher scores indicating better quality of life. There is no total score and the subscales are not combined.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Mar 2018
- Study start14 Jan 2018
- Primary completion30 Sep 2021
- Study completion30 Sep 2021
Why it stopped: PI left institution
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Social AnxietyStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Immediate therapy versus waitlist arms
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Tali Manber Ball, PhD, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03465137
- Sponsor's protocol ID
- IRB-44722
- Acronym
- UNFEAR
- Status last verified
- Sep 2021
- First submitted
- 7 Mar 2018
- Last updated
- 8 Oct 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: We plan to voluntarily share the raw fMRI data generated by this project through openfmri.org, a project of the Stanford Center for Reproducible Neuroscience. OpenfMRI is a recommended repository for several academic journals. There is no cost for researchers or analysts for use of this repository; the OpenfMRI repository uses a Public Domain license. We will fully de-identify and anonymize our data before uploading to the database, consistent with the OpenfMRI policy. Furthermore, the purpose, risks, and benefits of data sharing will be included in our consent form, and participants will be given the opportunity to exclude their data from the repository. Only participants who consent to and provide HIPAA authorization for this use will have their data uploaded.
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Developing a Mechanistic Neurobiological Model of Exposure Therapy Response Based on Fear Extinction Theory
- ClinicalTrials.gov ID
- NCT03465137
- Acronym / sponsor ID
- UNFEAR / IRB-44722
- Conditions
- Social Anxiety
- Keywords
- Exposure therapy, Behavioral therapy, fMRI, Extinction learning, Social anxiety
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI left institution
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 14 Jan 2018 (actual)
- Primary completion
- 30 Sep 2021 (actual)
- Study completion
- 30 Sep 2021 (actual)
- First posted
- 14 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Social anxiety disorder affects as many as 12% of Americans, resulting in significant distress and disability. Although exposure therapy is one of the best treatments available, as many as 25% of patients do not respond and we do not know why. Extinction learning is thought to be the mechanism of exposure therapy, and the neuroscience of extinction learning has advanced significantly since exposure therapy was developed; however, there has been little application towards improved clinical outcomes.
This project aims to improve exposure therapy response for patients with social anxiety disorder by directly linking exposure therapy response to the neurobiology of extinction learning. It also aims to increase our scientific understanding of how brain circuits work to support extinction learning. To do this, 80 adults with social anxiety disorder will randomly be assigned to either receive exposure therapy right away, or to wait before therapy. Participants will all complete a functional magnetic resonance imaging scan to assess extinction learning before the therapy.
Detailed description
The best available treatment for social anxiety disorder is exposure therapy; however, 25% of socially anxious patients do not respond to an adequate course of exposure therapy and it is unclear why. Prior attempts to identify non-responders using clinical and demographic features have been largely unsuccessful, highlighting the need to examine constructs that are more closely tied to the mechanism of treatment (i.e., extinction learning and recall) and the organ of dysfunction (i.e., the brain). The neurobiology of extinction learning and recall is well understood from decades of animal and pre-clinical laboratory work, which has highlighted the importance of the amygdala, dorsal anterior cingulate cortex (dACC), and ventromedial prefrontal cortex (vmPFC). However, this knowledge has not been leveraged to improve exposure therapy response, despite the assumption that response relies on extinction learning and its successful recall.
Thus, a critical long-term goal is to improve exposure therapy response by tailoring therapy based on the neurobiological profile of each patient. This project addresses that goal by directly linking neurobiological profiles of extinction learning and recall with clinical symptoms and therapy response. A major objective of this project is therefore to build a mechanistic predictive model of exposure therapy response based on the neurobiology of extinction learning and recall.
To accomplish this goal, the investigators will recruit 80 adults with social anxiety disorder who will be randomized to 10 sessions of exposure-focused therapy or waitlist. The primary clinical outcome measure will be the Liebowitz Social Anxiety Scale (LSAS), a validated and widely used measure that assesses anxiety and avoidance symptoms. Pre-therapy, participants will also undergo an experimental protocol for extinction learning and recall. Participants will first view a neutral abstract image repeatedly paired with a loud aversive noise, and another image that is never paired (fear acquisition phase). Following this, participants will view the same images without aversive consequences (extinction learning phase). Better extinction learning will be defined as greater reductions in skin conductance within the extinction learning phase. Brain activation during extinction learning will be assessed in the amygdala, dACC, and vmPFC. Finally, participants will view the same images without aversive consequences one week later (extinction recall phase). Better extinction recall will be defined as less skin conductance during extinction recall relative to fear acquisition. The central hypothesis is that greater activation in the vmPFC during extinction learning will predict both extinction recall and therapy response over and above symptom severity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Immediate therapy versus waitlist arms
| Arm | Type | Receives |
|---|---|---|
| Immediate therapy | Experimental | Behavioral: Coordinated Anxiety Learning and Management (CALM)Participants randomized to the immediate therapy arm will receive a weekly individual psychotherapy intervention called Coordinated Anxiety Learning and Management (CALM). The CALM program is an evidence based, exposure-focused therapy (http://calmtoolsforliving.org). Its computer-assisted format guides the therapist through psychoeducation, an introduction to cognitive restructuring, in-session and at-home exposures, and relapse prevention. Therapy will be delivered in 10 weekly 50-minute sessions within a 12 week period. |
| Waitlist | No intervention | –Participants randomized to the waitlist arm will receive no intervention for 12 weeks. After this 12 week period they will receive a the same weekly individual psychotherapy intervention as the immediate therapy group: Coordinated Anxiety Learning and Management (CALM). The CALM program is an evidence based, exposure-focused therapy (http://calmtoolsforliving.org). Its computer-assisted format guides the therapist through psychoeducation, an introduction to cognitive restructuring, in-session and at-home exposures, and relapse prevention. Therapy will be delivered in 10 weekly 50-minute sessions within a 12 week period. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- age 18-50
- primary diagnosis of social anxiety disorder
- fluent spoken and written English
- able to provide informed consent.
Key exclusion criteria (11 listed)
- history of mania or psychosis
- current moderate or severe substance use disorder
- current major depression greater than moderate severity
- high risk for suicide
- prior traumatic brain injury with loss of consciousness >5 minutes
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Coordinated Anxiety Learning and Management (CALM)Exposure-focused cognitive behavioral therapy | Behavioural | Immediate therapy |
Primary outcome
Liebowitz Social Anxiety Scale (LSAS)
Time frame: 12 weeks
A validated, widely-used measure of social anxiety severity, with anxiety and avoidance subscales. Subscales range from 0 to 72, with higher scores indicating greater anxiety and avoidance symptoms. A total score is computed by summing the two subscales (range: 0 to 144, higher scores indicate greater social anxiety severity).
3 secondary outcomes
Patient Health Questionnaire (PHQ-9)
Time frame: 12 weeks
Brief Fear of Negative Evaluation (BFNE)
Time frame: 12 weeks
World Health Organization Quality of Life scale (WHO-QOL)
Time frame: 12 weeks
Results and safety
The study was stopped early (reason given: PI left institution). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2021.
- Individual participant dataSharing planned: Yes. We plan to voluntarily share the raw fMRI data generated by this project through openfmri.org, a project of the Stanford Center for Reproducible Neuroscience. OpenfMRI is a recommended repository for several academic journals. There is no cost for researchers or analysts for use of this repository; the OpenfMRI repository uses a Public Domain license. We will fully de-identify and anonymize our data before uploading to the database, consistent with the OpenfMRI policy. Furthermore, the purpose, risks, and benefits of data sharing will be included in our consent form, and participants will be given the opportunity to exclude their data from the repository. Only participants who consent to and provide HIPAA authorization for this use will have their data uploaded.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Coordinated Anxiety Learning and Management (CALM) in people with Social Anxiety, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 8 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: PI left institution). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Liebowitz Social Anxiety Scale (LSAS) (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Oct 2021; AzTrials last refreshed its copy on 7 Nov 2026.