AnxietyNCT07415772
Effect of cTBS on Startle and TMS-evoked BOLD
A study testing Active TMS in people with Anxiety, run by University of Pennsylvania at 1 site in United States.
Trial summary
The right dorsolateral prefrontal cortex (dlPFC) is increasingly being targeted with transcranial magnetic stimulation (TMS) to reduce anxiety expression; however, there is little mechanistic evidence supporting an optimized treatment protocol. Read more about this study
- Who is it for?
- Ages 18 to 50 yearsHealthy volunteers can take part
- Conditions the study is for
- Anxiety
- What is being tested?
- Active TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 140 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2026to 30 Jun 2031
- 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 50 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Able to give their consent
- Right-handed
- Individuals receiving therapy for anxiety must be stable on their regimen for at least 4 weeks prior to study enrollment.
Who cannot join
- Non-english speaking
- Any significant medical or neurological problems
- Current or past non-anxiety-related psychiatric comorbidity, active or history of active suicidal ideation
- Alcohol/drug problems in the past year or lifetime alcohol or drug dependence
- Medications that act on the central nervous system
- History of seizure
Show all 15Show fewer
- History of epilepsy
- Increased risk of seizure for any reason
- Pregnancy, or positive pregnancy test
- Any medical condition that increases risk for fMRI or TMS
- Any metal in their body which would make having an MRI scan unsafe
- Any sort of medical implants
- Hearing loss
- Claustrophobia
- orthostatic hypotension
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
University of Pennsylvania
Philadelphia, Pennsylvania, 19104-6013
Nicholas Balderston, PhD, 215-746-3058, nicholas.balderston@pennmedicine.upenn.edu
About this study
Official title: The Effect of Right dlPFC cTBS on Acute Measures of Anxiety, Functional Connectivity, and TMS-evoked BOLD Responses.
The right dorsolateral prefrontal cortex (dlPFC) is increasingly being targeted with transcranial magnetic stimulation (TMS) to reduce anxiety expression; however, there is little mechanistic evidence supporting an optimized treatment protocol. Thus, the objective of the current project is to develop an interleaved TMS/fMRI that can assess the effect of neuromodulatory (potentially therapeutic) TMS protocols on neural and behavioral measures related to anxiety expression. PUBLIC HEALTH RELEVANCE: These results will yield direct evidence that 1 Hz and cTBS modulate brain activity associated with anxiety expression and regulation, thus informing novel TMS based anxiety treatments.
Read the detailed description
The right dorsolateral prefrontal cortex (dlPFC) is increasingly being targeted with transcranial magnetic stimulation (TMS) to reduce anxiety expression in anxiety disorders, depression, and posttraumatic stress disorder (PTSD). However, we lack the basic evidence to determine critical details regarding the optimal stimulation parameters including the dose, target, and protocol. In addition, there is little mechanistic evidence for why any particular right dlPFC target/dose/protocol should be effective for a given set of patients. Indeed, there is little consensus as to whether such mechanistic evidence should generalize across disorders. Accordingly, there is a critical need to understand the mechanisms of action underlying neuromodulatory right dlPFC TMS protocols, yet there is not a standardized protocol to yield such evidence. Without a reliable approach to approach to generate such information, it will be difficult or impossible to develop and optimize novel TMS treatments for disorders like PTSD and anxiety. The objective of the current project is to develop a protocol using interleaved TMS/fMRI that can assess the effect of neuromodulatory (potentially therapeutic) TMS protocols on neural and behavioral measures related to anxiety expression. Our central hypothesis is that inhibition of the right dlPFC via cTBS will also inhibit activity throughout its downstream targets, resulting in reduced anxiety, connectivity, and TMS-evoked responses among these downstream circuits during threat. Accordingly, our approach will be to measure anxious arousal, resting state functional connectivity, and TMS evoked BOLD responses before and immediately after 600 pulses of cTBS or sham stimulation in 100 high anxious individuals using a within-subjects crossover design. For anxious arousal, our primary outcome will be anxiety potentiated startle (APS) recorded with electromyography during the neutral, predictable, and unpredictable (NPU) threat paradigm administered in the lab before and after the scanning session. For the interleaved TMS/fMRI runs, our primary outcome will be TMS-evoked BOLD responses in these same downstream regions. This study is innovative because it is the first to combine these technologies to study the effect of neuromodulatory TMS on threat-related TMS-evoked BOLD responses. This project is significant because it will provide future researchers with an systematic approach for evaluating the effectiveness of neuromodulatory TMS protocols on several neural and behavioral indices of anxiety expression. It will also yield direct evidence that cTBS modulate brain activity associated with anxiety expression and regulation.
- Conditions
- Anxiety
- Being tested
- Active TMS, Sham TMS
- Keywords
- anxiety, transcranial magnetic stimulation
- Medical subject headings
- Anxiety Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active TMSDevice
Subjects will receive a continuous 1800 pulse cTBS train to the right dlPFC at 100% of motor threshold. The train will consist of 50 Hz bursts, repeated at intervals of 200 ms (5 Hz) for 40 sec.
Sham TMSDevice
Subjects will receive a series of 100 single pulses to the right dlPFC at 100% of motor threshold. Pulses will be randomly jittered and have an average interpulse interval of 6 ± 4 seconds. Single pulses delivered in such a fashion have been shown to have little or no neuromodulatory effect on subsequent cortical excitability.
| Study group | Role | What they receive |
|---|---|---|
| Transcranial Magnetic Stimulation | Other | A MagVenture MagPro 100X stimulator with a B91 figure-8 coil will be used for the TMS/fMRI rTMS sessions. Motor threshold testing will be done outside of the scanner using a separate MagVenture MagPro 100X with a separate B65 coil. Receives: Device: Active TMS; Device: Sham TMS |
What is being measured
The primary outcome is the main question the study is designed to answer.
TMS-evoked BOLD responses
Subjects will complete 16 minutes of high-resolution multi-band, multi-echo interleaved TMS/fMRI before and after the TMS. During these runs, subjects will receive periodic single pulses of TMS delivered to the right dlPFC. TMS-evoked BOLD responses to these pulses will be the primary outcome measure
Measured: Subjects will undergo 4 study visits spaced over a 5-week period. On visits 3 (week 2) and 4 (week 5), TMS-evoked BOLD responses will be recorded immediately (within 5 minutes) before and after the intervention.
Anxiety Potentiated Startle
Subjects will complete the NPU threat task. The primary outcome, APS, will be calculated by subtracting the blink magnitude during the neutral ITI from the unpredictable ITI. We hypothesize that cTBS will reduce APS compared to sham TMS.
Measured: Subjects will undergo 4 study visits spaced over a 5-week period. On visits 3 (week 2) and 4 (week 5), Anxiety Potentiated Startle will be recorded immediately (within 15 minutes) before and after the intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Feb 2026
- Study start1 Nov 2026 (estimated)
- Primary completion1 Jun 2031 (estimated)
- Study completion30 Jun 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AnxietyStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- 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
- Crossover
- Masking
- None (open label)
- Enrolment
- 140 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Nicholas Balderston, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07415772
- Sponsor's protocol ID
- 860105
- Status last verified
- Oct 2026
- First submitted
- 16 Jan 2026
- Last updated
- 14 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 14 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Right dlPFC cTBS on Acute Measures of Anxiety, Functional Connectivity, and TMS-evoked BOLD Responses.
- ClinicalTrials.gov ID
- NCT07415772
- Acronym / sponsor ID
- 860105
- Conditions
- Anxiety
- Keywords
- anxiety, transcranial magnetic stimulation
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 140 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 1 Nov 2026 (estimated)
- Primary completion
- 1 Jun 2031 (estimated)
- Study completion
- 30 Jun 2031 (estimated)
- First posted
- 17 Feb 2026 (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 right dorsolateral prefrontal cortex (dlPFC) is increasingly being targeted with transcranial magnetic stimulation (TMS) to reduce anxiety expression; however, there is little mechanistic evidence supporting an optimized treatment protocol. Thus, the objective of the current project is to develop an interleaved TMS/fMRI that can assess the effect of neuromodulatory (potentially therapeutic) TMS protocols on neural and behavioral measures related to anxiety expression. PUBLIC HEALTH RELEVANCE: These results will yield direct evidence that 1 Hz and cTBS modulate brain activity associated with anxiety expression and regulation, thus informing novel TMS based anxiety treatments.
Detailed description
The right dorsolateral prefrontal cortex (dlPFC) is increasingly being targeted with transcranial magnetic stimulation (TMS) to reduce anxiety expression in anxiety disorders, depression, and posttraumatic stress disorder (PTSD). However, we lack the basic evidence to determine critical details regarding the optimal stimulation parameters including the dose, target, and protocol. In addition, there is little mechanistic evidence for why any particular right dlPFC target/dose/protocol should be effective for a given set of patients. Indeed, there is little consensus as to whether such mechanistic evidence should generalize across disorders. Accordingly, there is a critical need to understand the mechanisms of action underlying neuromodulatory right dlPFC TMS protocols, yet there is not a standardized protocol to yield such evidence. Without a reliable approach to approach to generate such information, it will be difficult or impossible to develop and optimize novel TMS treatments for disorders like PTSD and anxiety. The objective of the current project is to develop a protocol using interleaved TMS/fMRI that can assess the effect of neuromodulatory (potentially therapeutic) TMS protocols on neural and behavioral measures related to anxiety expression. Our central hypothesis is that inhibition of the right dlPFC via cTBS will also inhibit activity throughout its downstream targets, resulting in reduced anxiety, connectivity, and TMS-evoked responses among these downstream circuits during threat. Accordingly, our approach will be to measure anxious arousal, resting state functional connectivity, and TMS evoked BOLD responses before and immediately after 600 pulses of cTBS or sham stimulation in 100 high anxious individuals using a within-subjects crossover design. For anxious arousal, our primary outcome will be anxiety potentiated startle (APS) recorded with electromyography during the neutral, predictable, and unpredictable (NPU) threat paradigm administered in the lab before and after the scanning session. For the interleaved TMS/fMRI runs, our primary outcome will be TMS-evoked BOLD responses in these same downstream regions. This study is innovative because it is the first to combine these technologies to study the effect of neuromodulatory TMS on threat-related TMS-evoked BOLD responses. This project is significant because it will provide future researchers with an systematic approach for evaluating the effectiveness of neuromodulatory TMS protocols on several neural and behavioral indices of anxiety expression. It will also yield direct evidence that cTBS modulate brain activity associated with anxiety expression and regulation.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Transcranial Magnetic Stimulation | Other | Device: Active TMS, Device: Sham TMSA MagVenture MagPro 100X stimulator with a B91 figure-8 coil will be used for the TMS/fMRI rTMS sessions. Motor threshold testing will be done outside of the scanner using a separate MagVenture MagPro 100X with a separate B65 coil. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Able to give their consent
- Right-handed
- Individuals receiving therapy for anxiety must be stable on their regimen for at least 4 weeks prior to study enrollment.
Key exclusion criteria (15 listed)
- Non-english speaking
- Any significant medical or neurological problems
- Current or past non-anxiety-related psychiatric comorbidity, active or history of active suicidal ideation
- Alcohol/drug problems in the past year or lifetime alcohol or drug dependence
- Medications that act on the central nervous system
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 |
|---|---|---|
| Active TMSSubjects will receive a continuous 1800 pulse cTBS train to the right dlPFC at 100% of motor threshold. The train will consist of 50 Hz bursts, repeated at intervals of 200 ms (5 Hz) for 40 sec. | Device | Transcranial Magnetic Stimulation |
| Sham TMSSubjects will receive a series of 100 single pulses to the right dlPFC at 100% of motor threshold. Pulses will be randomly jittered and have an average interpulse interval of 6 ± 4 seconds. Single pulses delivered in such a fashion have been shown to have little or no neuromodulatory effect on subsequent cortical excitability. | Device | Transcranial Magnetic Stimulation |
Primary outcome
TMS-evoked BOLD responses
Time frame: Subjects will undergo 4 study visits spaced over a 5-week period. On visits 3 (week 2) and 4 (week 5), TMS-evoked BOLD responses will be recorded immediately (within 5 minutes) before and after the intervention.
Subjects will complete 16 minutes of high-resolution multi-band, multi-echo interleaved TMS/fMRI before and after the TMS. During these runs, subjects will receive periodic single pulses of TMS delivered to the right dlPFC. TMS-evoked BOLD responses to these pulses will be the primary outcome measure
Anxiety Potentiated Startle
Time frame: Subjects will undergo 4 study visits spaced over a 5-week period. On visits 3 (week 2) and 4 (week 5), Anxiety Potentiated Startle will be recorded immediately (within 15 minutes) before and after the intervention.
Subjects will complete the NPU threat task. The primary outcome, APS, will be calculated by subtracting the blink magnitude during the neutral ITI from the unpredictable ITI. We hypothesize that cTBS will reduce APS compared to sham TMS.
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 14 Oct 2026.
- Individual participant dataSharing planned: Undecided
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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.
Nicholas Balderston, PhD principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active TMS in people with Anxiety, run by University of Pennsylvania 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 3 inclusion and 15 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: opening soon, as of the sponsor's last update on 14 Oct 2026. 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 Nicholas Balderston, PhD (12157463058, nicholas.balderston@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
TMS-evoked BOLD responses (time frame: Subjects will undergo 4 study visits spaced over a 5-week period. On visits 3 (week 2) and 4 (week 5), TMS-evoked BOLD responses will be recorded immediately (within 5 minutes) before and after the intervention.). The study lists 2 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 14 Oct 2026; AzTrials last refreshed its copy on 26 Oct 2026.