Post Traumatic Stress DisorderNCT05646732
Targeting the Default Mode Network: A TMS-fMRI Study
A study testing TMS-fMRI in people with Post Traumatic Stress Disorder and PTSD, run by Allyson Rosen at 1 site in United States.
Trial summary
In post-traumatic stress disorder (PTSD), intrusive, traumatic, autobiographical memories lead to anxiety symptoms. Recent work suggests a new repetitive pulse transcranial magnetic stimulation (rTMS) brain target that might bring relief. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Post Traumatic Stress Disorder, PTSD
- What is being tested?
- TMS-fMRI
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 2 Aug 2023to 31 Jan 2025
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Between 18 and 55 years of age
- Ability to maintain a Motor Threshold (MT) with single pulse TMS
- Ability to safely and comfortably undergo an MRI and TMS
- Able to read, verbalize, understand, and voluntarily sign the Informed Consent Form prior to participating in any study-specific procedures or assessments.
- PTSD diagnosis according to the DSM 5, as determined by the Clinician administered PTSD scale (CAPS-5) criteria.
- Commitment to maintaining a stable medication regimen between the two fMRI sessions
Who cannot join
- Inability to safely and comfortably undergo an MRI. MRI safety will be determined by the center where MRI's are collected.
- Inability to safely and comfortably undergo TMS. TMS exclusions include any history or condition that puts patients at risk.
- Significant dementia as determined by the Montreal Cognitive Assessments (MoCA)
- Common comorbid disorders of Veterans are allowed, but PTSD must be a primary diagnosis causing significant impairment that could not be accounted for by another diagnosis. Medical or mental health conditions that interact with or confound interpretation of PTSD symptoms and anxiety would be exclusionary.
- Being in urgent need of care that would make participation impossible
- Currently taking medications that increase the risk of seizure or influence hemodynamic response
- Presence of any other condition that has the potential to prevent study completion and/or have a confounding effect on the interpretation of results.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
VA Palo Alto
Palo Alto, California, 94304
James Lavacot, BA, 650-493-5000 ext. 65651, James.Lavacot@va.gov
Allyson C Rosen, PhD, 650-512-3094
About this study
In post-traumatic stress disorder (PTSD), intrusive, traumatic, autobiographical memories lead to anxiety symptoms. Recent work suggests a new repetitive pulse transcranial magnetic stimulation (rTMS) brain target that might bring relief. Since this proposed target is not well understood, the goal of the study is to use functional magnetic resonance imaging (fMRI) to identify the brain regions and networks that change with rTMS stimulation at this target area in PTSD patients. Ultimately, this would lead to a personalized approach to rTMS treatment of PTSD based on brain imaging that can be used in a future clinical trial.
Participants will be asked to complete psychological testing and questionnaires as well as an initial MRI and two separate TMS-fMRI sessions. Total participation time across all visits is estimated to be five to six hours.
Research participation will take place at VA Palo Alto as well as at Stanford University.
Read the detailed description
Post-traumatic stress disorder (PTSD) is a devastating illness in which traumatic autobiographical memories are intrusive and lead to anxiety symptoms. These symptoms align with functions of the default mode network (DMN) and, in fact, PTSD patients have abnormalities within the DMN and in its interactions with other networks, notably the salience network and the frontoparietal or central executive network.
Focal repetitive pulse transcranial magnetic stimulation (rTMS) enables neuromodulation of selected brain regions and connected networks to treat specific symptoms, but the brain targets to support this therapy in PTSD are under discovery. A recent analysis uncovered a brain circuit associated with improvement in anxiety and somatic symptoms following the rTMS treatment of depression. The left hemisphere region with the strongest fMRI functional connectivity with this circuit lies within anatomical area 8Av and the DMN. This association suggests that modulating the DMN through stimulation at left 8Av could be a novel rTMS approach for the treatment of anxiety and may help ameliorate anxiety symptoms in PTSD. This target would be novel since the vast majority of clinical trials of rTMS in PTSD have targeted the right frontal regions of the salience and frontoparietal networks instead of the DMN. One potential reason is that the most established nodes of the DMN do not lie directly below the scalp/skull and are thus unreachable by rTMS.
In this proposal, the overall hypothesis is that left area 8Av can serve as a robust, direct brain target for the DMN, thus facilitating therapy for PTSD and the many other disorders involving the DMN. Researchers will use TMS-fMRI in 30 participants with PTSD to test the causal connections between left 8Av and other regions that could mediate a response. Researchers will test the connectivity between 8Av and the inferior parietal lobe (IPL), a region in the DMN involved in context processing, and other nodes of the DMN (e.g., posterior cingulate, ventromedial prefrontal cortex). Pilot data suggests that the functional connection between 8Av and the IPL to be abnormal in people with anxiety relative to controls and that delivering rTMS to these regions ameliorates anxiety. This proposal will also explore whether stimulation at 8Av modulates the anterior insula, a node of the salience network whose functional connectivity predicts benefit from prolonged exposure therapy in PTSD. The TMS-induced BOLD response in these areas to stimulation of 8Av will be measured and compared to conventional seed-based resting-state fMRI functional connectivity analyses that could serve as an alternative marker for capacity for modulation. In addition, researchers will deliver theta burst rTMS (cTBS) stimulation and study how connectivity changes with respect to baseline. The overall goal is to characterize left 8Av functional connectivity in PTSD, and explore the effects of rTMS stimulation parameters. This project will thus provide a mechanistic understanding of rTMS therapy at 8Av, and will reveal the effects of a novel connectivity-based atlas target.
The participants in the study will come for three visits. During the first visit, participants will undergo MRI, psychological, and functional testing that will be used to characterize them as well as confirm their diagnoses and eligibility for the study. Participants will then undergo simultaneous TMS-fMRI and cTBS and fMRI in the second and third visits.
- Conditions
- Post Traumatic Stress Disorder, PTSD
- Being tested
- TMS-fMRI
- Keywords
- Transcranial Magnetic Stimulation, TMS, Magnetic Resonance Imaging, MRI, fMRI, TMS-fMRI
- 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.
TMS-fMRIDevice
Also called Simultaneous TMS and fMRI, Transcranial Magnetic Stimulation and Functional Magnetic Resonance Imaging
Participants will undergo simultaneous TMS and fMRI
| Study group | Role | What they receive |
|---|---|---|
| TMS-fMRI | Experimental | Participants will undergo simultaneous TMS-fMRI as part of this study. There will be two locations stimulated: one control region and one target region. Participants will be randomized with respect to the order of receiving stimulation at the locations, but all participants will receive stimulation at both locations as part of the study. All participants will be considered as one group but order effects will be evaluated as an explanatory variable. Receives: Device: TMS-fMRI |
What is being measured
The primary outcome is the main question the study is designed to answer.
Resting-State fMRI Connectivity
Measure of the connectivity between the left 8Av and DMN nodes.
Measured: During the resting state fMRI (rsfMRI) session
FMRI BOLD Response
Measure of the immediate activation (blood-oxygen-level-dependent change) in the brain regions related to PTSD following transcranial magnetic stimulation using interleaved TMS and fMRI.
Measured: During the TMS-fMRI session
Changes in Connectivity after cTBS
Measure of the connectivity changes between the left 8Av and DMN nodes from the initial resting state fMRI and a resting state fMRI collected immediately following inhibitory TMS (cTBS).
Measured: During the TMS-fMRI session
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Dec 2022
- Study start2 Aug 2023
- Primary completion31 Jan 2025 (estimated)
- Study completion31 Jan 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post Traumatic Stress DisorderStudies 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
- Not applicable
- Intervention model
- Single group
- Model description
- A mechanistic study using TMS-functional MRI
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Allyson Rosen
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor-investigator, Allyson Rosen, Palo Alto Veterans Institute for Research
- Investigators
- Allyson C Rosen, Ph.D., Principal investigator, PAVIR/Palo Alto VAHCS/Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05646732
- Sponsor's protocol ID
- ROANEW_0004
- Other IDs
- MH129799
- Status last verified
- Apr 2024
- First submitted
- 2 Dec 2022
- Last updated
- 3 Apr 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Researchers will not share the IPD without VA permission. The research team has requested guidance and if allowed, IPD may be shared, but for now there is no plan to share IPD. This statement will be updated if this changes.
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting the Default Mode Network: A TMS-fMRI Study
- ClinicalTrials.gov ID
- NCT05646732
- Acronym / sponsor ID
- ROANEW_0004
- Conditions
- Post Traumatic Stress Disorder, PTSD
- Keywords
- Transcranial Magnetic Stimulation, TMS, Magnetic Resonance Imaging, MRI, fMRI, TMS-fMRI
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Allyson RosenUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 2 Aug 2023 (actual)
- Primary completion
- 31 Jan 2025 (estimated)
- Study completion
- 31 Jan 2025 (estimated)
- First posted
- 12 Dec 2022 (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.
In post-traumatic stress disorder (PTSD), intrusive, traumatic, autobiographical memories lead to anxiety symptoms. Recent work suggests a new repetitive pulse transcranial magnetic stimulation (rTMS) brain target that might bring relief. Since this proposed target is not well understood, the goal of the study is to use functional magnetic resonance imaging (fMRI) to identify the brain regions and networks that change with rTMS stimulation at this target area in PTSD patients. Ultimately, this would lead to a personalized approach to rTMS treatment of PTSD based on brain imaging that can be used in a future clinical trial.
Participants will be asked to complete psychological testing and questionnaires as well as an initial MRI and two separate TMS-fMRI sessions. Total participation time across all visits is estimated to be five to six hours.
Research participation will take place at VA Palo Alto as well as at Stanford University.
Detailed description
Post-traumatic stress disorder (PTSD) is a devastating illness in which traumatic autobiographical memories are intrusive and lead to anxiety symptoms. These symptoms align with functions of the default mode network (DMN) and, in fact, PTSD patients have abnormalities within the DMN and in its interactions with other networks, notably the salience network and the frontoparietal or central executive network.
Focal repetitive pulse transcranial magnetic stimulation (rTMS) enables neuromodulation of selected brain regions and connected networks to treat specific symptoms, but the brain targets to support this therapy in PTSD are under discovery. A recent analysis uncovered a brain circuit associated with improvement in anxiety and somatic symptoms following the rTMS treatment of depression. The left hemisphere region with the strongest fMRI functional connectivity with this circuit lies within anatomical area 8Av and the DMN. This association suggests that modulating the DMN through stimulation at left 8Av could be a novel rTMS approach for the treatment of anxiety and may help ameliorate anxiety symptoms in PTSD. This target would be novel since the vast majority of clinical trials of rTMS in PTSD have targeted the right frontal regions of the salience and frontoparietal networks instead of the DMN. One potential reason is that the most established nodes of the DMN do not lie directly below the scalp/skull and are thus unreachable by rTMS.
In this proposal, the overall hypothesis is that left area 8Av can serve as a robust, direct brain target for the DMN, thus facilitating therapy for PTSD and the many other disorders involving the DMN. Researchers will use TMS-fMRI in 30 participants with PTSD to test the causal connections between left 8Av and other regions that could mediate a response. Researchers will test the connectivity between 8Av and the inferior parietal lobe (IPL), a region in the DMN involved in context processing, and other nodes of the DMN (e.g., posterior cingulate, ventromedial prefrontal cortex). Pilot data suggests that the functional connection between 8Av and the IPL to be abnormal in people with anxiety relative to controls and that delivering rTMS to these regions ameliorates anxiety. This proposal will also explore whether stimulation at 8Av modulates the anterior insula, a node of the salience network whose functional connectivity predicts benefit from prolonged exposure therapy in PTSD. The TMS-induced BOLD response in these areas to stimulation of 8Av will be measured and compared to conventional seed-based resting-state fMRI functional connectivity analyses that could serve as an alternative marker for capacity for modulation. In addition, researchers will deliver theta burst rTMS (cTBS) stimulation and study how connectivity changes with respect to baseline. The overall goal is to characterize left 8Av functional connectivity in PTSD, and explore the effects of rTMS stimulation parameters. This project will thus provide a mechanistic understanding of rTMS therapy at 8Av, and will reveal the effects of a novel connectivity-based atlas target.
The participants in the study will come for three visits. During the first visit, participants will undergo MRI, psychological, and functional testing that will be used to characterize them as well as confirm their diagnoses and eligibility for the study. Participants will then undergo simultaneous TMS-fMRI and cTBS and fMRI in the second and third visits.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A mechanistic study using TMS-functional MRI
| Arm | Type | Receives |
|---|---|---|
| TMS-fMRI | Experimental | Device: TMS-fMRIParticipants will undergo simultaneous TMS-fMRI as part of this study. There will be two locations stimulated: one control region and one target region. Participants will be randomized with respect to the order of receiving stimulation at the locations, but all participants will receive stimulation at both locations as part of the study. All participants will be considered as one group but order effects will be evaluated as an explanatory variable. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Between 18 and 55 years of age
- Ability to maintain a Motor Threshold (MT) with single pulse TMS
- Ability to safely and comfortably undergo an MRI and TMS
- Able to read, verbalize, understand, and voluntarily sign the Informed Consent Form prior to participating in any study-specific procedures or assessments.
- PTSD diagnosis according to the DSM 5, as determined by the Clinician administered PTSD scale (CAPS-5) criteria.
Key exclusion criteria (7 listed)
- Inability to safely and comfortably undergo an MRI. MRI safety will be determined by the center where MRI's are collected.
- Inability to safely and comfortably undergo TMS. TMS exclusions include any history or condition that puts patients at risk.
- Significant dementia as determined by the Montreal Cognitive Assessments (MoCA)
- Common comorbid disorders of Veterans are allowed, but PTSD must be a primary diagnosis causing significant impairment that could not be accounted for by another diagnosis. Medical or mental health conditions that interact with or confound interpretation of PTSD symptoms and anxiety would be exclusionary.
- Being in urgent need of care that would make participation impossible
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 |
|---|---|---|
| TMS-fMRIAlso: Simultaneous TMS and fMRI, Transcranial Magnetic Stimulation and Functional Magnetic Resonance ImagingParticipants will undergo simultaneous TMS and fMRI | Device | TMS-fMRI |
Primary outcome
Resting-State fMRI Connectivity
Time frame: During the resting state fMRI (rsfMRI) session
Measure of the connectivity between the left 8Av and DMN nodes.
FMRI BOLD Response
Time frame: During the TMS-fMRI session
Measure of the immediate activation (blood-oxygen-level-dependent change) in the brain regions related to PTSD following transcranial magnetic stimulation using interleaved TMS and fMRI.
Changes in Connectivity after cTBS
Time frame: During the TMS-fMRI session
Measure of the connectivity changes between the left 8Av and DMN nodes from the initial resting state fMRI and a resting state fMRI collected immediately following inhibitory TMS (cTBS).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2024.
- Individual participant dataSharing planned: No. Researchers will not share the IPD without VA permission. The research team has requested guidance and if allowed, IPD may be shared, but for now there is no plan to share IPD. This statement will be updated if this changes.
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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.
Allyson C Rosen, Ph.D. principal investigator
PAVIR/Palo Alto VAHCS/Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing TMS-fMRI in people with Post Traumatic Stress Disorder and PTSD, run by Allyson Rosen at 1 site in United States.
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 6 inclusion and 7 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: looking for participants now, as of the sponsor's last update on 3 Apr 2024. 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 United States. 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact James Lavacot, BA (6504935000 ext. 65651, james.lavacot@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Resting-State fMRI Connectivity (time frame: During the resting state fMRI (rsfMRI) session). 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 3 Apr 2024.