Psychotherapy of Anxiety Disorders With Noninvasive Brain Stimulation - Using Virtual Reality

Nicht-invasive Hirnstimulation in Der Psychotherapie Von Angsterkrankungen

The aim of the study is to transfer the rTMS stimulation protocol by Raij et al. (2018) into a therapeutic setting to improve exposure therapy in acrophobic patients. The quasi-randomized, placebo-controlled and double-blinded study will include 88 patients with height phobia (according to DSM 5). All participants will perform two exposure sessions in virtual reality (VR). Before exposure therapy, one group will receive verum rTMS of the left frontal cortex, which is indirectly functionally linked to the ventromedial prefrontal cortex (Raij et al., 2018). The control group will receive sham stimulation. A structural MRI and a TMS navigation system will be used for precise localization of the left FC. Anxiety symptoms will be measured using subjective ratings (e.g. Acrophobia Questionnaire) and the behavioural approach task (BAT) in VR and in real life before and after the treatment, and at 6 months follow-up. Furthermore, blood samples will be collected before rTMS and after exposure treatment to assess epigenetic and gene expression based changes.

Study Overview

• Status: Completed
• Conditions: Phobia
• Intervention / Treatment: Device: Verum TMS; Device: Sham TMS

Detailed Description

The following hypotheses are derived:

1. Patients with acrophobia, who receive an active rTMS of the left FC before VRET, show a significantly stronger reduction of phobic symptoms immediately after exposure therapy, compared to the sham stimulation group.
2. Patients with acrophobia, who receive an active rTMS of the left FC before VRET, show a significantly greater increase in approach behavior and significantly less distress during the BAT immediately after exposure therapy, compared to the sham stimulation group.
3. The postulated differences in hypotheses 1 and 2 are still detectable at follow-up after 6 months.

• Study Type: Interventional
• Enrollment (Actual): 87
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Würzburg, Germany, 97080
    • Martin J. Herrmann

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Acrophobia (according to DSM-5)
• Right handed
• German native speaker
• Written informed consent

Exclusion Criteria:

• Neurological and/or severe physical illnesses
• Comorbid Axis I disorder (other than phobias)
• Pretreated phobia of heights
• Use of tricyclic antidepressants, antipsychotics, or other substances that increase cerebral seizure susceptibility
• Craniocerebral injuries, head surgery
• Epileptic seizures, or family history of epilepsy
• Metal parts in the head area
• Cardiac pacemakers
• Infusion pumps
• Heart diseases
• Increased intracranial pressure
• Pregnancy
• Cochlear implants
• Tattoos (done before the year 2000)
• Piercings (if not completely removable)
• Permanent make-up
• Nicotine or pain patches
• other MRI contraindications

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Verum TMS; ITBS (intermittent Theta Burst Stimulation) over left frontal cortex	Device: Verum TMS; Intensity of 100% of the resting motor threshold with iTBS. 600 stimuli applied in bursts of three pulses at 50 Hz given every 200 ms. iTBS will be applied 20 times for 2 s every 10 s.; Other Names: Cool-B70 A/P, MagPro X100, MagVenture®, Denmark
Sham Comparator: Sham TMS; Sham TMS over left frontal cortex	Device: Sham TMS; Sham stimulation with same protocol, but without magnetic stimulation; Other Names: Cool-B70 A/P, MagPro X100,, MagVenture®, Denmark

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective anxiety symptoms	Acrophobia Questionnaire (Cohen, 1977) with two subscales: 1) degree of anxiety (ACRO) and 2) degree of avoidance (AVOI) in height-related situations.	change from T1 (baseline /study start) to T4 (immediately after treatment)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective anxiety in behavioral approach tests (BAT)	anxiety measurement by a behavioral approach test (BAT) in virtual reality (glass elevator on the outside of an high-rise building, height up to 150m) and in real life (open stairwell height up to 11,6m).	change from T1 (baseline /study start) to T4 (immediately after treatment)
Subjective anxiety symptoms (Follow-Up)	Acrophobia Questionnaire (Cohen, 1977) with two subscales: 1) degree of anxiety (ACRO) and 2) degree of avoidance (AVOI) in height-related situations.	change from T1 (baseline/ study start) to T28 (6 months follow-up)
Subjective anxiety in behavioral approach tests (BAT) (Follow-Up)	anxiety measurement by a behavioral approach test (BAT) in virtual reality (glass elevator on the outside of an high-rise building, height up to 150m) and in real life (open stairwell height up to 11,6m).	change from T1 (baseline /study start) to T28 (6 months follow-up)

Collaborators and Investigators

• Sponsor: Wuerzburg University Hospital
• Collaborators: University of Wuerzburg
• Investigators: Principal Investigator: Martin J. Herrmann, PhD, University of Würzburg

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2021
• Primary Completion (Actual): September 27, 2022
• Study Completion (Actual): April 28, 2023

Study Registration Dates

• First Submitted: February 23, 2021
• First Submitted That Met QC Criteria: March 3, 2021
• First Posted (Actual): March 4, 2021

Study Record Updates

• Last Update Posted (Actual): August 2, 2023
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: rTMS; Exposure therapy; VR; PFC; Acrophobia
• Other Study ID Numbers: Wuerzburg45/20-am; PAN_VR (Other Identifier: Clinic for Psychiatry)

Drug and device information, study documents

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