Virtual Reality Exposure in Spider Phobia

Study Overview
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Brief Summary
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While knowledge on the neurobiological signatures of fear and anxiety disorders and, in particular, their association with treatment outcome is accumulating, clinical translation still awaits empirical proof of evidence. Exposure-based cognitive-behavioral therapy (CBT) is a first-line treatment, but clinically significant change is only seen in approx. 50-65% of patients. Patient stratification is a powerful option to increase treatment response; however, developing prognostic markers suitable for single-patient predictions still is in its infancy and crucially requires external cross-validation embedded within an a priori prediction approach - a procedure yet largely missing in the field of biomarker research. Employing a bicentric strategy the aim of this study is to test the hypothesis that a priori prediction of treatment outcome based on neurobiological measures is possible in a second, independent sample. Building upon findings from previous mechanistic studies, These will be incorporated into the development of a predictive pattern comprising fear-relevant genotypes and molecules targeting neuropeptides, related epigenetic signatures as well as neurofunctional activation patterns associated with fear circuitry functions, and clinical data. Pre-treatment neurobiological signatures will be tested for their potential as a predictive response marker towards behavioral exposure (virtual reality exposure treatment (VRET) and an in vivo behavioral avoidance test) in a model disorder of fear circuitry dysfunctions (spider phobia). Multivariate pattern analyses employing a machine learning framework will be used to generate predictions on the individual patient level and to cross-validate markers in a second, independent sample. While at site A predictions will be generated following completion of the treatment, response will be predicted at site B a priori, but in a double-blind manner. Comparison of observed vs. predicted response rates will serve as a test of hypothesis. In addition, neuroplastic (on a subsample) and epigenetic changes induced by VRET treatment will be assessed following treatment and, in case of epigenetics, also after 6-months follow-up.

Official Title
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Exposure Treatment in Anxiety Disorders: Proof of Principle for an a Priori Response Prediction Approach

Conditions
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Specific Phobia, Cognitive-behavioral Therapy, Virtual Reality

Intervention / Treatment
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* Behavioral: virtual reality exposure


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 or older specific phobia (animal subtype: spider phobia) according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, 5th Version (DSM-5) right-handedness Caucasian descent willingness to participate in massed exposure Exclusion Criteria: patients exhibiting a primary other anxiety disorder (panic disorder, agoraphobia, social phobia, generalized anxiety disorder), acute suicidality, psychotic, bipolar I, obsessive-compulsive disorder, posttraumatic stress disorder, severe major depression, borderline personality disorder or substance dependency (except nicotine) patients fulfilling MRI-related exclusion criteria patients with current pharmacological or psychotherapeutic treatment, as well as those already previously treated with exposure-based CBT pregnancy or lactation

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: virtual reality exposure<br>one-session exposure conveyed via virtual reality technology | Behavioral: virtual reality exposure<br>* one-session exposure conveyed via virtual reality technology<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spider Phobia Questionnaire (SPQ) | Change in spider phobia symptoms before (baseline) to after therapy | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Behavioral Avoidance Text (BAT) | Change (in cm) in the extend to which a living spider can be approached from before to after therapy | 4 weeks | 
| Behavioral Avoidance Text (BAT) | Change (in cm) in the extend to which a living spider can be approached from before vs. after 6 month follow-up period | 6 months | 
| Clinical Global Impressions (CGI) | Clinician rated symptom severity after completion of treatment (4 weeks) | 4 weeks | 
| Clinical Global Impressions (CGI) | Clinician rated symptom severity after 6 month follow-up period | 6 month | 
| Spider Phobia Questionnaire (SPQ) | Change in spider phobia symptoms before (baseline) vs. after 6 month follow-up period | 6 months |