NCT03208400

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
338

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Sep 2017

Typical duration for not_applicable

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 28, 2017

Completed
7 days until next milestone

First Posted

Study publicly available on registry

July 5, 2017

Completed
2 months until next milestone

Study Start

First participant enrolled

September 1, 2017

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 31, 2019

Completed
9 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 10, 2020

Completed
Last Updated

February 11, 2020

Status Verified

February 1, 2020

Enrollment Period

1.7 years

First QC Date

June 28, 2017

Last Update Submit

February 10, 2020

Conditions

Specific PhobiaCognitive-behavioral TherapyVirtual Reality

Outcome Measures

Primary Outcomes (1)

  • Spider Phobia Questionnaire (SPQ)

    Change in spider phobia symptoms before (baseline) to after therapy

    4 weeks

Secondary Outcomes (5)

  • Behavioral Avoidance Text (BAT)

    4 weeks

  • Behavioral Avoidance Text (BAT)

    6 months

  • Clinical Global Impressions (CGI)

    4 weeks

  • Clinical Global Impressions (CGI)

    6 month

  • Spider Phobia Questionnaire (SPQ)

    6 months

Study Arms (1)

virtual reality exposure

OTHER

one-session exposure conveyed via virtual reality technology

Behavioral: virtual reality exposure

Interventions

virtual reality exposureBEHAVIORAL

one-session exposure conveyed via virtual reality technology

virtual reality exposure

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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 with current pharmacological or psychotherapeutic treatment, as well as those already previously treated with exposure-based CBT
  • pregnancy or lactation

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Center of Mental Health, Dept. of Psychiatry, Psychosomatics, and Psychiatry, University Hospital of Wuerzburg

Würzburg, Bavaria, 97080, Germany

Location

Dept. of Psychiatry, University Hospital Münster

Münster, North Rhine-Westphalia, 48149, Germany

Location

Related Publications (4)

  • 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.

    PMID: 31814209BACKGROUND

  • Chavanne AV, Meinke C, Langhammer T, Roesmann K, Boehnlein J, Gathmann B, Herrmann MJ, Junghoefer M, Klahn L, Schwarzmeier H, Seeger FR, Siminski N, Straube T, Dannlowski U, Lueken U, Leehr EJ, Hilbert K. Individual-Level Prediction of Exposure Therapy Outcome Using Structural and Functional MRI Data in Spider Phobia: A Machine-Learning Study. Depress Anxiety. 2023 Aug 22;2023:8594273. doi: 10.1155/2023/8594273. eCollection 2023.

    PMID: 40224607DERIVED

  • Langhammer T, Hilbert K, Adolph D, Arolt V, Bischoff S, Bohnlein J, Cwik JC, Dannlowski U, Deckert J, Domschke K, Evens R, Fydrich T, Gathmann B, Hamm AO, Heinig I, Herrmann MJ, Hollandt M, Junghoefer M, Kircher T, Koelkebeck K, Leehr EJ, Lotze M, Margraf J, Mumm JLM, Pittig A, Plag J, Richter J, Roesmann K, Ridderbusch IC, Schneider S, Schwarzmeier H, Seeger F, Siminski N, Straube T, Strohle A, Szeska C, Wittchen HU, Wroblewski A, Yang Y, Straube B, Lueken U. Resting-state functional connectivity in anxiety disorders: a multicenter fMRI study. Mol Psychiatry. 2025 Apr;30(4):1548-1557. doi: 10.1038/s41380-024-02768-2. Epub 2024 Oct 4.

    PMID: 39367057DERIVED

  • Roesmann K, Leehr EJ, Bohnlein J, Gathmann B, Herrmann MJ, Junghofer M, Schwarzmeier H, Seeger FR, Siminski N, Straube T, Dannlowski U, Lueken U. Mechanisms of action underlying virtual reality exposure treatment in spider phobia: Pivotal role of within-session fear reduction. J Anxiety Disord. 2023 Dec;100:102790. doi: 10.1016/j.janxdis.2023.102790. Epub 2023 Oct 14.

    PMID: 37879242DERIVED

MeSH Terms

Conditions

Phobia, Specific

Interventions

Virtual Reality Exposure Therapy

Intervention Hierarchy (Ancestors)

Desensitization, PsychologicBehavior TherapyPsychotherapyBehavioral Disciplines and Activities

Study Officials

  • Ulrike Lueken, Prof. Dr.

    University Hospital of Wuerzburg

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Prof. Dr.

Study Record Dates

First Submitted

June 28, 2017

First Posted

July 5, 2017

Study Start

September 1, 2017

Primary Completion

May 31, 2019

Study Completion

February 10, 2020

Last Updated

February 11, 2020

Record last verified: 2020-02

Data Sharing

IPD Sharing
Will not share

Locations

DE(2)