Virtual Reality Exposure in Spider Phobia

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

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.

Study Overview

• Status: Completed
• Conditions: Specific Phobia; Virtual Reality; Cognitive-behavioral Therapy
• Intervention / Treatment: Behavioral: virtual reality exposure

• Study Type: Interventional
• Enrollment (Actual): 338
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Bavaria
    • Wuerzburg, Bavaria, Germany, 97080
      • Center of Mental Health, Dept. of Psychiatry, Psychosomatics, and Psychiatry, University Hospital of Wuerzburg
  • North Rhine-Westphalia
    • Münster, North Rhine-Westphalia, Germany, 48149
      • Dept. of Psychiatry, University Hospital Münster

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
OTHER: virtual reality exposure; one-session exposure conveyed via virtual reality technology	Behavioral: virtual reality exposure; one-session exposure conveyed via virtual reality technology

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Julius-Maximilians University
• Collaborators: University Hospital Muenster
• Investigators: Principal Investigator: Ulrike Lueken, Prof. Dr., University Hospital of Wuerzburg

Publications and helpful links

General Publications

• Schwarzmeier H, Leehr EJ, Bohnlein J, Seeger FR, Roesmann K, Gathmann B, Herrmann MJ, Siminski N, Junghofer M, Straube T, Grotegerd D, Dannlowski U. Theranostic markers for personalized therapy of spider phobia: Methods of a bicentric external cross-validation machine learning approach. Int J Methods Psychiatr Res. 2020 Jun;29(2):e1812. doi: 10.1002/mpr.1812. Epub 2019 Dec 8.

Study record dates

Study Major Dates

• Study Start (ACTUAL): September 1, 2017
• Primary Completion (ACTUAL): May 31, 2019
• Study Completion (ACTUAL): February 10, 2020

Study Registration Dates

• First Submitted: June 28, 2017
• First Submitted That Met QC Criteria: June 30, 2017
• First Posted (ACTUAL): July 5, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 11, 2020
• Last Update Submitted That Met QC Criteria: February 10, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Anxiety Disorders; Phobic Disorders
• Other Study ID Numbers: Spider_VR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No