Clinical trial NCT03208400: Virtual Reality Exposure in Spider Phobia
Official title: Exposure Treatment in Anxiety Disorders: Proof of Principle for an a Priori Response Prediction Approach
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Specific Phobia
Cognitive-behavioral Therapy
Virtual Reality
Lead sponsor: Julius-Maximilians University
Sponsor class: OTHER
Collaborators: name: University Hospital Muenster
First posted: 2017-07-05
Enrollment: 338
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Spider Phobia Questionnaire (SPQ)
timeFrame: 4 weeks
Secondary outcomes:
measure: Behavioral Avoidance Text (BAT)
timeFrame: 4 weeks
measure: Behavioral Avoidance Text (BAT)
timeFrame: 6 months
measure: Clinical Global Impressions (CGI)
timeFrame: 4 weeks
measure: Clinical Global Impressions (CGI)
timeFrame: 6 month
measure: Spider Phobia Questionnaire (SPQ)
timeFrame: 6 months
Other outcomes:
Locations:
city: Wuerzburg
country: Germany
facility: Center of Mental Health, Dept. of Psychiatry, Psychosomatics, and Psychiatry, University Hospital of Wuerzburg
state: Bavaria
city: Münster
country: Germany
facility: Dept. of Psychiatry, University Hospital Münster
state: North Rhine-Westphalia
Study officials:
affiliation: University Hospital of Wuerzburg
name: Ulrike Lueken, Prof. Dr.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.