Reduction of Trauma-induced Intrusions and Amygdala Hyperreactivity Via Non-invasive Brain Stimulation

Post Traumatic Stress Disorder Clinical Trial

— COOL  

Official title:

Reduction of Trauma-induced Intrusions and Amygdala Hyperreactivity Via Non-invasive Brain Stimulation

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04325087
• Other study ID #: COOL
• Status: Recruiting
• Phase: N/A
• Start date: July 1, 2019
• Est. completion date: May 30, 2020

Study information

• Verified date: March 2020
• Source: University Hospital, Bonn
• Contact: Dirk Scheele, PhD
• Phone: +49 (0)228 287
• Email: Dirk.Scheele[@]ukb.uni-bonn.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: May 30, 2020
• Est. primary completion date: May 30, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Intrusive Thoughts
• Post Traumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic

Intervention

Device:
• iTBS
Administration of an iTBS protocol over the dlPFC
• Placebo iTBS
Administration of a placebo TMS protocol over the dlPFC

Locations

Country	Name	City	State
Germany	Department of Psychiatry, University of Bonn	Bonn

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bonn

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number and quality of intrusive thoughts	Sum and stress ratings of intrusive thoughts measured on three consecutive days after trauma exposure by an online questionnaire.	Three days after trauma exposure
Primary	Changes in resting state functional connectivity	Functional connectivity data will be assessed by two 10-minutes resting state fMRI scans before and after three sessions of TMS treatment over the course of three days. The resting state fMRI analysis will focus on changes in functional connectivity between regions-of-interest (ROIs) associated with intrusive memories (prefrontal cortex, amygdala, precuneus, insula, hippocampus, cingulate cortex). Changes in functional connectivity between the first and second fMRI sessions will be computed on the first level and independent t-tests will be used to compare the verum and sham TMS groups.	10-minutes resting state fMRI scans before and after three sessions of TMS treatment
Primary	Changes in neural response to an emotion recognition task	Changes between the first and second fMRI session in the blood-oxygen-level-dependent (BOLD) signal in response to happy, fearful and neutral faces as well as houses will be compared between the experimental groups. Analysis will focus on anatomically defined regions-of-interest (ROI) associated with emotion processing (i.e. amygdala, prefrontal cortex, insula, striatal areas). Changes in the neural response and functional connectivity between the first and second fMRI sessions will be computed on the first level and independent t-tests will be used to compare the verum and sham TMS groups. For analyses of fMRI data, standard procedures of the software SPM12 will be used.	15-minutes emotional face matching fMRI task before and after three sessions of TMS treatment
Secondary	Changes in executive functioning (One Touch Stockings of Cambridge) and attention (Rapid Visual Information Processing) during iTBS treatment	Cognitive tasks conducted with the CanTab software will be used to measure executive functioning (One Touch Stockings of Cambridge) and attention (Rapid Visual Information Processing) on four different time points during the treatment (pre/post first iTBS, pre/post last iTBS). Changes in executive functioning and attention will be tested as moderator variables of other TMS effects.	15-minutes cognitive tasks pre/post first iTBS and pre/post last iTBS treatment
Secondary	Trauma disclosure	Trauma disclosure will be measured by online questionnaires on days 2-4. Subjects will be asked to report the number and duration (in minutes) of conversations about the video. Furthermore, subjects have to report to who they talked with about the video. Trauma disclosure will be tested as a moderator variable of TMS effects.	Three days after trauma exposure
Secondary	Changes in electrodermal responses to the trauma video	Electrodermal responses will be recorded by a BioNomadix System (BIOPAC Systems Inc., Santa Barbara, USA) during a 5-minutes baseline before the start of the trauma video and during the trauma video with two electrodes attached to palm of the right hand.	5 minutes before and during the trauma video
Secondary	Respiratory changes in response to the trauma video	Respiratory rate will be recorded by a BioNomadix System (BIOPAC Systems Inc., Santa Barbara, USA) during a 5-minutes baseline before the start of the trauma video and during the trauma video with belt attached to the subject's chest. Data will be analyzed for changes in breathing frequency and amplitude in response to the trauma video.	5 minutes before and during the trauma video
Secondary	Heart rate changes in response to the trauma video	Heart rate will be recorded by a BioNomadix System (BIOPAC Systems Inc., Santa Barbara, USA) during a 5-minutes baseline before the start of the trauma video and during the trauma video.	5 minutes before and during the trauma video
Secondary	Changes in positive and and negative affect in response to the trauma video	Changes in positive and negative affect will be measured by the PANAS (Positive and Negative Affect Schedule) questionnaire 10 minutes before and 10 minutes after trauma exposure. The PANAS questionnaire consists of two subscale: 1. positive affect (minimum rating = 5, maximum rating = 50), 2. negative affect (minimum rating = 5, maximum rating = 50).	10 minutes before and 10 minutes after trauma exposure
Secondary	Changes in anxiety in response to the trauma video	Changes in anxiety will be measured by the STAI-Trait (State-Trait Anxiety Inventory) questionnaire immediately 10 minutes before and 10 minutes after trauma exposure.(minimum rating = 20, maximum rating = 80, higher values indicate more state anxiety).	10 minutes before and 10 minutes after trauma exposure
Secondary	Dissociative symptoms after trauma exposure	Dissociative symptoms after the trauma video will be measured by questionnaires (Dissociation-Tension-Scale acute) and tested as a moderator variable of TMS effects. Subjects score between 0 and 9, with higher values indicating more dissociative symptoms.	10 minutes after trauma exposure
Secondary	Childhood maltreatment	The Childhood Trauma Questionnaire (CTQ) will be used to measure childhood maltreatment. The scale ranges between 5 and 100 points and higher scores indicate higher childhood maltreatment. CTQ scores will be tested as moderator variable of TMS effects.	Before first fMRI scan
Secondary	Sleep quality: visual analog scales	Sleep quality (delay in sleep onset, calmness, depth of sleep, nightmares, nightly awakenings) will be measured with visual analog scales from 0 to 100. Higher scores represent poor sleep quality.	Three days after trauma exposure
Secondary	Delayed discounting task	To test changes in PFC-associated control of impulsive preferences, subjects will perform a delayed discounting paradigm. Participants will be asked to choose between small immediate rewards and larger later rewards. This task will be conducted twice (before and after the iTBS sessions).	Before and three days after trauma exposure
Secondary	Food craving task	Food craving will be measured twice (before and after the iTBS sessions). Participants will be confronted with pictures of candy and dessert in two types of trials. In "NOW" trials, participants will be instructed to consider the immediate consequence of consuming the pictured food, while "LATER" trials will direct participants to think about the long-term consequences.	Before and three days after trauma exposure

External Links

•   Neuromodulation of Emotion (NEMO) research group