Posttraumatic Stress DisorderNCT06234969
A Mechanistic Trial of the Neurobiology of Extinction Learning and Intraparietal Sulcus Stimulation
A study testing Continuous Theta Burst Stimulation to the Intraparietal Sulcus in people with Posttraumatic Stress Disorder, run by University of Pennsylvania at 1 site in United States.
Trial summary
This study will be the first of its kind to explore the impact of continuous theta burst stimulation (cTBS) to the intraparietal sulcus (IPS) on arousal symptoms among patients with posttraumatic stress disorder (PTSD). Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Posttraumatic Stress Disorder
- What is being tested?
- Continuous Theta Burst Stimulation to the Intraparietal Sulcus
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Apr 2024to 31 Oct 2028
- 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 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Adult aged 18-60
- Meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for PTSD according to the Clinician-Administered PTSD Scale for DSM-5
- No metal implants
Who cannot join
- Pregnancy
- Seizure disorder or epilepsy
- Increased risk of seizure
- Non-English speaking
- Any medical condition that increases risk for fMRI or cTBS
- Medical implant
Show all 10Show fewer
- Hearing loss sufficient to interfere with startle
- Claustrophobia
- Recent medication or therapy changes (in the past 8 weeks)
- Current severe substance use disorder
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
Center for the Treatment and Study of Anxiety, University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Lily A Brown, PhD, 215-746-3346, lilybr@pennmedicine.upenn.edu
Sonalee Joshi, PhD, 21-746-3342, sonalee.joshi@pennmedicine.upenn.edu
About this study
This study will be the first of its kind to explore the impact of continuous theta burst stimulation (cTBS) to the intraparietal sulcus (IPS) on arousal symptoms among patients with posttraumatic stress disorder (PTSD). The investigators will demonstrate that IPS cTBS results in significant reduction in arousal (measured by startle response) compared to sham cTBS, that IPS cTBS interacts with extinction training to further improve arousal, and that there is a dose/response effect of cTBS on arousal. The investigators will also demonstrate that IPS cTBS significantly improves retention of extinction learning, the experimental analogue of exposure therapy.
Read the detailed description
Posttraumatic stress disorder (PTSD) is associated with alterations in arousal that do not respond well to evidence-based practices. Patients with PTSD tend to fall into one of two groups in extinction training (and in exposure therapy): 1) over-engagers, where arousal is too high; and 2) under-engagers, where patients are so worried about becoming upset that they distract themselves from the task (which prevents learning). In this mechanistic clinical trial, the investigators will evaluate a strategy to augment extinction training with neuromodulation to reduce arousal and improve extinction retention. Augmenting extinction training with continuous theta burst stimulation (cTBS, a type of transcranial magnetic stimulation) delivered to the intraparietal sulcus (IPS) may lead to targeted reductions in arousal. The investigative team has shown that the IPS is a "connectivity hub" for arousal and that stimulating this region with TMS can reduce excessive arousal in healthy people. The goal for this R01 is to evaluate the main effects of IPS cTBS (versus sham cTBS, a between-subject comparison) and its interaction with extinction training (vs. neutral training) on arousal among patients with PTSD. The investigators hypothesize that reducing parietal hyperexcitability will help patients with PTSD to modulate arousal during extinction training-enough arousal to ensure that they can benefit, but not too much arousal which prevents learning. These results could translate into future opportunities for novel therapeutic targets among patients with PTSD. The specific aims are as follows: Aim 1: To evaluate the optimal dose of IPS cTBS. H1: Attenuation of startle for IPS cTBS vs. sham cTBS will plateau at 1200 pulses, the anticipated optimal cumulative dose. Aim 2: To compare the main effect of IPS cTBS and its interaction with extinction training on arousal (measured by startle response). Using a two (between group: sham vs. IPS cTBS) x 2 (within group: extinction training vs. control/neutral training) randomized controlled design among patients with PTSD (N = 120), the investigators will examine the potential benefit of cTBS and extinction training on reduction in arousal. H2a: IPS cTBS will result in greater reduction in arousal compared to sham cTBS. H2b: Participants who receive IPS cTBS will have a significantly lower difference in retention of extinction learning vs. control/neutral training (indicative of greater retention of extinction learning) compared to participants who receive sham cTBS. Secondary: The investigators will test analogous hypotheses on subjective outcomes and on cognitive outcomes and the investigators hypothesize similar directions of effects. Aim 3: To evaluate neural mechanisms of action of IPS cTBS + extinction training. Participants will complete a resting state fMRI scan on tests of retention of learning experimental visits to evaluate neural changes from training. H3: The investigators will observe attenuated activation (relative to pre-test) of the IPS for participants who received IPS cTBS compared to those who received sham cTBS.
- Conditions
- Posttraumatic Stress Disorder
- Being tested
- Continuous Theta Burst Stimulation to the Intraparietal Sulcus, Sham Continuous Theta Burst Stimulation
- 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.
Continuous Theta Burst Stimulation to the Intraparietal SulcusDevice
Continuous Theta Burst Stimulation delivered to the Intraparietal Sulcus
Sham Continuous Theta Burst StimulationDevice
Sham Continuous Theta Burst Stimulation
| Study group | Role | What they receive |
|---|---|---|
| Continuous theta burst stimulation to the intraparietal sulcus | Experimental | Continuous theta burst stimulation will be delivered to the individually targeted intraparietal sulcus site at 100% RMT. Receives: Device: Continuous Theta Burst Stimulation to the Intraparietal Sulcus |
| Sham continuous theta burst stimulation | Placebo comparator | We will use the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the pulse to mimic actual stimulation. Receives: Device: Sham Continuous Theta Burst Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Electromyography startle response
Startle will be recorded from the left orbicularis oculi at 2000 Hz.
Measured: Days 4, 5, 34 and 35
Secondary outcomes (3)
Subjective Units of Distress (SUDS)
We will assess SUDS using the prompt "On a scale from 0 - 10, how distressed does this recording make you?"
Measured: Days 4, 5, 34 and 35
Negative outcome expectancy
On a scale from 0 ("certain no negative outcome") to 10 ("certain negative outcome"), how certain are you that the negative outcome will happen as you listen this script?
Measured: Days 4, 5, 34 and 35
fMRI
We will collect resting state functional connectivity.
Measured: Days 2, 5, and 35
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2024
- Study start29 Apr 2024
- Primary completion31 Jul 2028 (estimated)
- Study completion31 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Posttraumatic Stress DisorderStudies 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
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Lily A Brown, PhD, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06234969
- Sponsor's protocol ID
- 849571
- Status last verified
- Oct 2025
- First submitted
- 22 Jan 2024
- Last updated
- 30 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: We will share data through the NIMH Data Archive using only de-identified data connected through the global unique identifier (GUID).
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Mechanistic Trial of the Neurobiology of Extinction Learning and Intraparietal Sulcus Stimulation
- ClinicalTrials.gov ID
- NCT06234969
- Acronym / sponsor ID
- 849571
- Conditions
- Posttraumatic Stress Disorder
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 29 Apr 2024 (actual)
- Primary completion
- 31 Jul 2028 (estimated)
- Study completion
- 31 Oct 2028 (estimated)
- First posted
- 31 Jan 2024 (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.
This study will be the first of its kind to explore the impact of continuous theta burst stimulation (cTBS) to the intraparietal sulcus (IPS) on arousal symptoms among patients with posttraumatic stress disorder (PTSD). The investigators will demonstrate that IPS cTBS results in significant reduction in arousal (measured by startle response) compared to sham cTBS, that IPS cTBS interacts with extinction training to further improve arousal, and that there is a dose/response effect of cTBS on arousal. The investigators will also demonstrate that IPS cTBS significantly improves retention of extinction learning, the experimental analogue of exposure therapy.
Detailed description
Posttraumatic stress disorder (PTSD) is associated with alterations in arousal that do not respond well to evidence-based practices. Patients with PTSD tend to fall into one of two groups in extinction training (and in exposure therapy): 1) over-engagers, where arousal is too high; and 2) under-engagers, where patients are so worried about becoming upset that they distract themselves from the task (which prevents learning). In this mechanistic clinical trial, the investigators will evaluate a strategy to augment extinction training with neuromodulation to reduce arousal and improve extinction retention. Augmenting extinction training with continuous theta burst stimulation (cTBS, a type of transcranial magnetic stimulation) delivered to the intraparietal sulcus (IPS) may lead to targeted reductions in arousal. The investigative team has shown that the IPS is a "connectivity hub" for arousal and that stimulating this region with TMS can reduce excessive arousal in healthy people. The goal for this R01 is to evaluate the main effects of IPS cTBS (versus sham cTBS, a between-subject comparison) and its interaction with extinction training (vs. neutral training) on arousal among patients with PTSD. The investigators hypothesize that reducing parietal hyperexcitability will help patients with PTSD to modulate arousal during extinction training-enough arousal to ensure that they can benefit, but not too much arousal which prevents learning. These results could translate into future opportunities for novel therapeutic targets among patients with PTSD. The specific aims are as follows: Aim 1: To evaluate the optimal dose of IPS cTBS. H1: Attenuation of startle for IPS cTBS vs. sham cTBS will plateau at 1200 pulses, the anticipated optimal cumulative dose. Aim 2: To compare the main effect of IPS cTBS and its interaction with extinction training on arousal (measured by startle response). Using a two (between group: sham vs. IPS cTBS) x 2 (within group: extinction training vs. control/neutral training) randomized controlled design among patients with PTSD (N = 120), the investigators will examine the potential benefit of cTBS and extinction training on reduction in arousal. H2a: IPS cTBS will result in greater reduction in arousal compared to sham cTBS. H2b: Participants who receive IPS cTBS will have a significantly lower difference in retention of extinction learning vs. control/neutral training (indicative of greater retention of extinction learning) compared to participants who receive sham cTBS. Secondary: The investigators will test analogous hypotheses on subjective outcomes and on cognitive outcomes and the investigators hypothesize similar directions of effects. Aim 3: To evaluate neural mechanisms of action of IPS cTBS + extinction training. Participants will complete a resting state fMRI scan on tests of retention of learning experimental visits to evaluate neural changes from training. H3: The investigators will observe attenuated activation (relative to pre-test) of the IPS for participants who received IPS cTBS compared to those who received sham cTBS.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Continuous theta burst stimulation to the intraparietal sulcus | Experimental | Device: Continuous Theta Burst Stimulation to the Intraparietal SulcusContinuous theta burst stimulation will be delivered to the individually targeted intraparietal sulcus site at 100% RMT. |
| Sham continuous theta burst stimulation | Placebo comparator | Device: Sham Continuous Theta Burst StimulationWe will use the coil's electric stimulation functionality that allows for the delivery of a brief electric pulse to the scalp simultaneous to the pulse to mimic actual stimulation. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Adult aged 18-60
- Meets Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria for PTSD according to the Clinician-Administered PTSD Scale for DSM-5
- No metal implants
Key exclusion criteria (10 listed)
- Pregnancy
- Seizure disorder or epilepsy
- Increased risk of seizure
- Non-English speaking
- Any medical condition that increases risk for fMRI or cTBS
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 |
|---|---|---|
| Continuous Theta Burst Stimulation to the Intraparietal SulcusContinuous Theta Burst Stimulation delivered to the Intraparietal Sulcus | Device | Continuous theta burst stimulation to the intraparietal sulcus |
| Sham Continuous Theta Burst StimulationSham Continuous Theta Burst Stimulation | Device | Sham continuous theta burst stimulation |
Primary outcome
Electromyography startle response
Time frame: Days 4, 5, 34 and 35
Startle will be recorded from the left orbicularis oculi at 2000 Hz.
3 secondary outcomes
Subjective Units of Distress (SUDS)
Time frame: Days 4, 5, 34 and 35
Negative outcome expectancy
Time frame: Days 4, 5, 34 and 35
fMRI
Time frame: Days 2, 5, and 35
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 30 Oct 2025.
- Individual participant dataSharing planned: Yes. We will share data through the NIMH Data Archive using only de-identified data connected through the global unique identifier (GUID).
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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.
Lily A Brown, 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 Continuous Theta Burst Stimulation to the Intraparietal Sulcus in people with Posttraumatic Stress Disorder, 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 10 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 30 Oct 2025. 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. 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?
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 Lily A Brown, PhD (2157463346, lilybr@pennmedicine.upenn.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Electromyography startle response (time frame: Days 4, 5, 34 and 35). 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 30 Oct 2025.