Clinical trial NCT04325087: Reduction of Trauma-induced Intrusions and Amygdala Hyperreactivity Via Non-invasive Brain Stimulation
Official title: Reduction of Trauma-induced Intrusions and Amygdala Hyperreactivity Via Non-invasive Brain Stimulation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Intrusive Thoughts
Post Traumatic Stress Disorder
Keywords: Amygdala
fMRI
Intrusive Thoughts
Post Traumatic Stress Disorder
TMS
Lead sponsor: University Hospital, Bonn
Sponsor class: OTHER
First posted: 2020-03-27
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants receive either three sessions of iTBS over the dorsolateral prefrontal cortex or three sessions of a placebo stimulation.
Primary purpose: BASIC_SCIENCE

Brief summary: The study will focus on the modulation of intrusive memories via functional magnetic resonance imaging (fMRI)-guided repetitive transcranial magnetic stimulation of the dorsolateral prefrontal cortex (dlPFC) directly after exposure to a traumatic video.

Detailed description: Traumatic experiences can lead to posttraumatic stress disorder (PTSD) with clinical manifestations including intrusions, avoidance behavior, and hyperarousal. Unlike most other psychological disorders, a PTSD diagnosis requires a clearly identifiable inciting event. As such, preventive interventions in recently traumatized individuals seem promising.

In this randomized, placebo-controlled study the investigators explore the potential of individualized transcranial magnetic stimulation (TMS) to reduce trauma-induced intrusive thoughts by altering functional connectivity between the dorsolateral prefrontal cortex (dlPFC) and amygdala. Subjects will undergo a functional magnetic resonance imaging (fMRI) session consisting of a resting state scan, an emotion recognition task and an anatomical scan at the beginning of the study (day 1). Resting state data will be used to determine individualized TMS targets for every subject, depending on functional connectivity between the dlPFC and amygdala. Subsequently, the analogue trauma model will be used to induce intrusions in healthy subjects. Subjects will be confronted with a video clip from the movie "Irreversible" and they will complete online questionnaires in the following three days to measure intrusive thoughts, trauma disclosure (i.e. duration of conversations about the aversive movie) and sleeping quality. Intermittent theta-burst stimulation (iTBS) will be administered directly after the video clip and on the following two days (day 2-4). Cognitive tasks will be applied before and after iTBS sessions to examine short-term effects of iTBS on a behavioral level. Finally, subjects will undergo a second fMRI session similar to the first one, to probe iTBS-induced changes in functional connectivity and emotional processing (day 5).

Eligibility criteria: Inclusion Criteria:

* Healthy subjects

Exclusion Criteria:

* current psychiatric illness
* current psychiatric medication or psychotherapy
* past PTSD diagnosis
* MRI contraindication (e.g. metal in body, claustrophobia)
* pregnancy

Primary outcomes:
measure: Number and quality of intrusive thoughts
timeFrame: Three days after trauma exposure
measure: Changes in resting state functional connectivity
timeFrame: 10-minutes resting state fMRI scans before and after three sessions of TMS treatment
measure: Changes in neural response to an emotion recognition task
timeFrame: 15-minutes emotional face matching fMRI task before and after three sessions of TMS treatment
Secondary outcomes:
measure: Changes in executive functioning (One Touch Stockings of Cambridge) and attention (Rapid Visual Information Processing) during iTBS treatment
timeFrame: 15-minutes cognitive tasks pre/post first iTBS and pre/post last iTBS treatment
measure: Trauma disclosure
timeFrame: Three days after trauma exposure
measure: Changes in electrodermal responses to the trauma video
timeFrame: 5 minutes before and during the trauma video
measure: Respiratory changes in response to the trauma video
timeFrame: 5 minutes before and during the trauma video
measure: Heart rate changes in response to the trauma video
timeFrame: 5 minutes before and during the trauma video
measure: Changes in positive and and negative affect in response to the trauma video
timeFrame: 10 minutes before and 10 minutes after trauma exposure
measure: Changes in anxiety in response to the trauma video
timeFrame: 10 minutes before and 10 minutes after trauma exposure
measure: Dissociative symptoms after trauma exposure
timeFrame: 10 minutes after trauma exposure
measure: Childhood maltreatment
timeFrame: Before first fMRI scan
measure: Sleep quality: visual analog scales
timeFrame: Three days after trauma exposure
measure: Delayed discounting task
timeFrame: Before and three days after trauma exposure
measure: Food craving task
timeFrame: Before and three days after trauma exposure
Other outcomes:
Locations:
city: Bonn
country: Germany
facility: Department of Psychiatry, University of Bonn
Study officials:
affiliation: University of Oldenburg
name: Rene Hurlemann, MSc, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: