Clinical Trial Details
— Status: Terminated
Administrative data
| NCT number |
NCT03135990 |
| Other study ID # |
1701017878 |
| Secondary ID |
|
| Status |
Terminated |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
August 14, 2018 |
| Est. completion date |
March 23, 2020 |
Study information
| Verified date |
February 2022 |
| Source |
Weill Medical College of Cornell University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Anxiety disorders are the most common mental health diagnosis in the US and are associated
with avoidance that causes functional impairments and decreases quality of life. Social
anxiety disorder is among the most prevalent anxiety disorders, with most common age of onset
being in adolescence. The frontline treatment for social anxiety disorder is cognitive
behavioral therapy with exposure. However, a significant number of adolescent patients do not
get better after completing cognitive behavioral therapy or experience relapse. This could be
explained by findings in both mice and humans suggesting that cue-based extinction learning
occurs less readily in adolescents than in children and adults. Studies using mouse-models
have overcome this age disparity by enhancing contextual cues when fear extinction learning
takes place. Providing realistic learning contexts for exposure could be the key to enhancing
treatment effects in adolescents. This is often challenging for a variety of reasons,
including difficulty realistically mimicking anxiety-provoking social situations due to
limited resources, clinician training, time, or motivation. Virtual reality environments
could provide contextual exposures for social anxiety.
This pilot study will test the feasibility of integrating virtual reality technology in
exposure-based treatment in youth ages 13-23 diagnosed with social anxiety disorder with the
goal of approximating equivalent efficacy with traditional cognitive behavioral therapy, and
assessing feasibility of virtual reality technology with this population. We will also pilot
a fear conditioning and extinction learning paradigm to explore the relationship between
extinction learning and efficacy of virtual reality exposure therapy, using physiological
assessment indicators to mark changes in fear response. These markers will also be used prior
to the initiation of the therapy to assess the degree to which virtual reality environments
invoke a true fear response, comparing the 12 participants with social phobia to 12 age
matched, non-anxious control participants. The aims of this study are threefold: to assess
feasibility of using virtual reality in treatment of social anxiety in youth, to examine
whether virtual reality invokes arousal similar to anxiety and test the physiological
assessment protocol, and to evaluate whether exposure using virtual reality environments
reduces symptoms of social anxiety and related functional impairment.
Description:
Lifetime prevalence of social anxiety disorder in adolescents is estimated to be 8.6%, with
the most common age of onset being ages 15-17. Social anxiety disorder is related to
significant functional impairment and, if untreated, puts youth at risk for depression and
substance abuse, and results in failure to meet important academic, social, and occupational
milestones. The current literature supports cognitive behavioral therapy with exposure
therapy, selective serotonin re-uptake inhibitor medications, and their combination for the
treatment of anxiety disorders with good effects. However, even with gold standard treatment,
a significant number of patients do not get better or experience relapse. Exposure therapy is
based on the principles of fear extinction, such that cues associated with threat are
presented in a safe and controlled way until they are experienced as safe and fear responses
are reduced. Studies in mice and non-anxious humans have demonstrated cue-based fear
extinction learning to be less robust in adolescence than it is in childhood or adulthood.
However, mouse-models suggest that context-based extinction learning closes the gap between
age-groups, with adolescents performing as well on extinction learning tasks when put back in
the original environment where the fear was acquired.
Similarly, clinical research suggest that exposure therapy is most useful when exposures are
conducted in the same or similar environments to where the fear is experienced in everyday
life. However, there are many barriers to providing contextual based exposure therapy,
particularly for social anxiety, including paucity of well-trained exposure therapists in
many areas of the country, and difficulty generating or accessing realistic social situations
for convincing exposures.
Virtual reality offers a promising avenue for contextual exposures, by increasing the
availability of certain contexts that cannot be readily mimicked in therapy. Furthermore, in
vivo exposure situations can feel overwhelming for some individuals (patients and
therapists), resulting in refusal to engage in exposure altogether. Virtual reality
technology could allow for more gradual titration of exposure for those patients that require
lower intensity exposures, and can be done in the therapy office for clinicians who do not
have the time, resources, experience, or comfort level to travel outside of their office in
pursuit of appropriate exposure environments. Even for seasoned exposure therapists, virtual
reality could serve as a practice step in preparation for in vivo exposures or could be used
in lieu of in vivo exposures if necessary. There has been extensive research on the use of
virtual reality in facilitating exposure in a variety of populations. However, its
effectiveness has not been demonstrated in adolescents with social phobia, and research is
limited in adolescent samples in general.
The pilot study proposed for this National Alliance for Research on Schizophrenia and
Depression award would test the overall hypothesis that virtual reality technology is
feasible, acceptable, and will enhance exposure-based therapy for socially anxious youth.
Studies will be focused on testing the feasibility of integrating virtual reality technology
into exposure-based treatment in adolescents and young adults (ages 13-23) diagnosed with
social anxiety disorder with the goal of approximating equivalent efficacy with traditional
cognitive behavioral therapy, and assessing feasibility, usability, and acceptability of the
virtual reality technology with this population. In addition, we would pilot a fear
conditioning and extinction learning paradigm with the subjects to explore the relationship
between extinction learning and efficacy of virtual reality exposure therapy, using
physiological assessment indicators to mark changes in fear response, including skin
conductance, heart rate, heart rate variability, and startle. These physiological markers
would also be used prior to the initiation of the therapy to assess the degree to which the
virtual reality environments invoke a true fear response, comparing the 12 subjects with
social phobia to 12 age-matched, non-anxious control subjects. If feasible and effective,
these procedures would be used for a larger future study, and pilot data would be used for a
K-award, R21, or R01 grant application, including neuroimaging to learn more about the neural
circuitry involved in fear learning via virtual reality technology.
SPECIFIC AIMS
Specific Aim 1: To assess the feasibility, acceptability, and usability of simulated exposure
using virtual reality environments in treatment of social anxiety in youth ages 13-23.
Hypothesis: We hypothesize that the use of this technology will be feasible, evidenced by 75%
completion of the treatment protocol.
Specific Aim 2: To examine the degree to which virtual reality environments invoke arousal
consistent with anxiety, and test the feasibility, acceptability, and usability of
psychophysiological assessment protocol.
Hypothesis: We hypothesize that subjects will exhibit elevated arousal during virtual
reality-assisted exposures, evidenced by increased skin conductance, heart rate, and startle
response, and expect the procedures to be feasible and acceptable as evidenced by high
completion and low drop out.
Specific Aim 3: To evaluate the impact of simulated exposure using virtual reality
environments in reducing symptoms of social anxiety and related functional impairment.
Hypothesis: We hypothesize that subjects will exhibit a decrease in anxiety evidenced by
reduction in Anxiety Disorders Interview Schedule Clinician Severity Rating ≤ 4 and
improvement in global functioning evidenced by Clinical Global Impression- Improvement rating
≤ 3.
METHODS
Study Design: 12 adolescents and young adults (ages 13- 23) with social anxiety disorder
(cognitive behavioral therapy + virtual reality), and 12 age-matched comparison subjects
(Controls) will be recruited for participation in this pilot feasibility study. Subjects on
psychiatric medication must be on a stable dose for at least 2 months prior to study
participation and remain symptomatic to the level identified for inclusion in the cognitive
behavioral therapy + virtual reality group (Anxiety Disorders Interview Schedule Clinician
Severity Rating ≥ 4). Controls must not meet criteria for any anxiety disorder. Control
subjects will not complete the intervention, but will participate solely in the initial
virtual reality arousal test and the fear extinction paradigm.
Assessment measures: Clinician administered measures include the Anxiety Disorder Interview
Schedule for DSM 5 to determine initial diagnostic status. The Clinical Global Impression
Scale (CGI) will assess overall symptom severity and improvement. Self-report measures
include the Screen for Child Anxiety Related Disorders and the World Health Organization
Disability Scale-12 assessment of global functioning. Subjects in the virtual reality +
cognitive behavioral therapy group will complete these measures at pre-treatment, at
post-treatment, and at 3 month follow up. Controls will complete these measures at only one
time point.
Virtual Reality technology: virtual reality simulation allows subjects wearing a head-mounted
display to view computer-generated 3-D imagery of a variety of social environments which
evoke distress in individuals diagnosed with social anxiety. Subjects report on distress
levels throughout the exercise.
Cognitive Behavioral Therapy Intervention: The manualized cognitive behavioral therapy
intervention used in this study will be a modified version of the Unified Protocol for
Emotional Disorders in Youth (UP-Y), which is a modular cognitive behavioral therapy protocol
for anxiety disorders and depression with demonstrated efficacy in youth. The modular
approach allows for patient engagement in exposure therapy at earliest readiness, and also
allows for the structured implementation of other cognitive behavioral therapy components.
The 10-session intervention includes psychoeducation about anxiety disorders and their
treatment (1 session), emotion awareness and regulation (2 sessions), exposure therapy using
virtual reality environments (6 sessions), and review and relapse prevention (1 session). All
treatment sessions will be videotaped to ensure fidelity to treatment manual and modules.
Psychophysiological measures: The Biopac system will measure physiological arousal through
measures of skin conductance, heart rate, heart rate variability, and startle response (via
eye blink reflex). Each of the tests involved in collection of biological measures is a
standard, non-painful and non-invasive procedure.
Fear Conditioning & Extinction Paradigm: Subjects will participate in a laboratory test of
extinction training during their initial assessment in order to establish extinction learning
as a potential predictive marker of treatment outcome. Subjects will be exposed to two shapes
on a computer screen, one shape (conditioned stimulus; CS+) will be paired with an aversive
stimulus (unconditioned stimulus) on 38% of the trials, whereas the other shape will never be
paired with aversive stimulus (conditioned stimulus-). Later, they will undergo extinction
training in which the two conditioned stimuli will be repeatedly presented without the
unconditioned stimulus. Extinction will be measured as the difference score of skin
conductance response to the conditioned stimulus+ and conditioned stimulus-.
