Intrusive ThoughtsCOOLNCT04325087
Reduction of Trauma-induced Intrusions and Amygdala Hyperreactivity Via Non-invasive Brain Stimulation
A study testing iTBS in people with Intrusive Thoughts and Post Traumatic Stress Disorder, run by University Hospital, Bonn at 1 site in Germany.
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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Intrusive Thoughts, Post Traumatic Stress Disorder
- What is being tested?
- iTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteGermany
- Study dates
- 1 Jul 2019to 30 May 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy subjects
Who cannot join
- current psychiatric illness
- current psychiatric medication or psychotherapy
- past PTSD diagnosis
- MRI contraindication (e.g. metal in body, claustrophobia)
- pregnancy
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
Department of Psychiatry, University of Bonn
Bonn, 53105
Dirk Scheele, PhD, +49 (0)228 287 ext. 11151, Dirk.Scheele@ukb.uni-bonn.de
Mitjan Morr, MSc, +49 (0)228 287 ext. 19578, Mitjan.Morr@ukbonn.de
About this study
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.
Read the 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).
- Conditions
- Intrusive Thoughts, Post Traumatic Stress Disorder
- Being tested
- iTBS, Placebo iTBS
- Keywords
- Amygdala, fMRI, Intrusive Thoughts, Post Traumatic Stress Disorder, TMS
- Medical subject headings
- Stress Disorders, Post-Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
iTBSDevice
Administration of an iTBS protocol over the dlPFC
Placebo iTBSDevice
Administration of a placebo TMS protocol over the dlPFC
| Study group | Role | What they receive |
|---|---|---|
| Active iTBS | Experimental | Active stimulation of the dlPFC directly after trauma exposure and on the following two days Receives: Device: iTBS |
| Placebo iTBS | Placebo comparator | Same procedure as in the active stimulation group but with a placebo stimulation imitating the sensation of a real iTBS protocol. Receives: Device: Placebo iTBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Three days after trauma exposure
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.
Measured: 10-minutes resting state fMRI scans before and after three sessions of TMS treatment
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.
Measured: 15-minutes emotional face matching fMRI task before and after three sessions of TMS treatment
Secondary outcomes (12)
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.
Measured: 15-minutes cognitive tasks pre/post first iTBS and pre/post last iTBS treatment
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.
Measured: Three days after trauma exposure
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.
Measured: 5 minutes before and during the trauma video
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.
Measured: 5 minutes before and during the trauma video
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.
Measured: 5 minutes before and during the trauma video
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).
Measured: 10 minutes before and 10 minutes after trauma exposure
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).
Measured: 10 minutes before and 10 minutes after trauma exposure
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.
Measured: 10 minutes after trauma exposure
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.
Measured: Before first fMRI scan
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.
Measured: Three days after trauma exposure
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).
Measured: Before and three days after trauma exposure
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.
Measured: Before and three days after trauma exposure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Mar 2020
- Study start1 Jul 2019
- Primary completion30 May 2020 (estimated)
- Study completion30 May 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Intrusive ThoughtsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants receive either three sessions of iTBS over the dorsolateral prefrontal cortex or three sessions of a placebo stimulation.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Hospital, Bonn
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rene Hurlemann, University Hospital, Bonn
- Investigators
- Rene Hurlemann, MSc, MD, PhD, Principal investigator, University of Oldenburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04325087
- Sponsor's protocol ID
- COOL
- Acronym
- COOL
- Status last verified
- Mar 2020
- First submitted
- 28 Feb 2020
- Last updated
- 27 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Reduction of Trauma-induced Intrusions and Amygdala Hyperreactivity Via Non-invasive Brain Stimulation
- ClinicalTrials.gov ID
- NCT04325087
- Acronym / sponsor ID
- COOL / COOL
- Conditions
- Intrusive Thoughts, Post Traumatic Stress Disorder
- Keywords
- Amygdala, fMRI, Intrusive Thoughts, Post Traumatic Stress Disorder, TMS
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University Hospital, BonnUniversity, hospital or other
- Study start
- 1 Jul 2019 (actual)
- Primary completion
- 30 May 2020 (estimated)
- Study completion
- 30 May 2020 (estimated)
- First posted
- 27 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Participants receive either three sessions of iTBS over the dorsolateral prefrontal cortex or three sessions of a placebo stimulation.
| Arm | Type | Receives |
|---|---|---|
| Active iTBS | Experimental | Device: iTBSActive stimulation of the dlPFC directly after trauma exposure and on the following two days |
| Placebo iTBS | Placebo comparator | Device: Placebo iTBSSame procedure as in the active stimulation group but with a placebo stimulation imitating the sensation of a real iTBS protocol. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Healthy subjects
Key exclusion criteria (5 listed)
- current psychiatric illness
- current psychiatric medication or psychotherapy
- past PTSD diagnosis
- MRI contraindication (e.g. metal in body, claustrophobia)
- pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| iTBSAdministration of an iTBS protocol over the dlPFC | Device | Active iTBS |
| Placebo iTBSAdministration of a placebo TMS protocol over the dlPFC | Device | Placebo iTBS |
Primary outcome
Number and quality of intrusive thoughts
Time frame: Three days after trauma exposure
Sum and stress ratings of intrusive thoughts measured on three consecutive days after trauma exposure by an online questionnaire.
Changes in resting state functional connectivity
Time frame: 10-minutes resting state fMRI scans before and after three sessions of TMS treatment
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.
Changes in neural response to an emotion recognition task
Time frame: 15-minutes emotional face matching fMRI task before and after three sessions of TMS treatment
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.
12 secondary outcomes
Changes in executive functioning (One Touch Stockings of Cambridge) and attention (Rapid Visual Information Processing) during iTBS treatment
Time frame: 15-minutes cognitive tasks pre/post first iTBS and pre/post last iTBS treatment
Trauma disclosure
Time frame: Three days after trauma exposure
Changes in electrodermal responses to the trauma video
Time frame: 5 minutes before and during the trauma video
Respiratory changes in response to the trauma video
Time frame: 5 minutes before and during the trauma video
Heart rate changes in response to the trauma video
Time frame: 5 minutes before and during the trauma video
Changes in positive and and negative affect in response to the trauma video
Time frame: 10 minutes before and 10 minutes after trauma exposure
Changes in anxiety in response to the trauma video
Time frame: 10 minutes before and 10 minutes after trauma exposure
Dissociative symptoms after trauma exposure
Time frame: 10 minutes after trauma exposure
Childhood maltreatment
Time frame: Before first fMRI scan
Sleep quality: visual analog scales
Time frame: Three days after trauma exposure
Delayed discounting task
Time frame: Before and three days after trauma exposure
Food craving task
Time frame: Before and three days after trauma exposure
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Mar 2020.
- Neuromodulation of Emotion (NEMO) research groupLink provided by the sponsor.
- Individual participant dataSharing planned: No
Related trials for Intrusive Thoughts
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rene Hurlemann, MSc, MD, PhD principal investigator
University of Oldenburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing iTBS in people with Intrusive Thoughts and Post Traumatic Stress Disorder, run by University Hospital, Bonn at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Dirk Scheele, PhD (+49 (0)228 287 ext. 11151, Dirk.Scheele@ukb.uni-bonn.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number and quality of intrusive thoughts (time frame: Three days after trauma exposure). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Mar 2020.