Intensive PTSD Treatment Combined With Transcranial Magnetic Stimulation: A Pilot Study
Phase: NA
Conditions: PTSD
Sponsor: Rush University Medical Center

Addressing Intensive PTSD Treatment Non-Response Via Transcranial Magnetic Stimulation: A 
Pilot Study 
 
NCT06271733 
 
3/7/2025 

Addressing Intensive PTSD Treatment Non-Response Via Transcranial Magnetic 
Stimulation: A Pilot Study 
Principal Investigator: Philip Held, Ph.D.
Co-Principal Investigator: Sheila M. Dowd, Ph.D.
Study Coordinator: Sarah Pridgen, M.A.
Abstract:
The 2- and 3-week Cognitive Processing Therapy-based intensive treatment program for 
veterans with PTSD at Rush University Medical Center’s Road Home Program (RHP) has been 
shown to be highly effective (Zalta et al., 2018; Held et al., 2020). Close to 60% of all veterans 
who complete the program no longer meet the diagnostic criteria for PTSD upon treatment 
completion and over 75% experience significant symptom reductions (Held et al., 2020). Despite 
its demonstrated effectiveness, not all veterans benefit equally from treatment. 
Although the rate of treatment non-responders in the Intensive Outpatient Program (IOP) at the 
Road Home Program at Rush (~25%) compares favorably to traditional PTSD treatment (30-
51%; Steenkamp et al., 2015), it is important to explore alternatives to our regular programing in 
which can help the ~25% who do not experience a meaningful reduction in PTSD or symptoms. 
The goal of this study is to determine whether complementing regular intensive PTSD treatment 
with intermittent theta burst stimulation (iTBS) applied to the right dorsolateral prefrontal cortex 
(DLPFC) can improve treatment response for individuals who are likely non-responders. 
Specifically, the present study will evaluate iTBS  during the second week of the 2-week IOP for 
veterans and service members who have not experienced PTSD symptom reductions over the 
course of the first week of the Road Home Program intensive PTSD treatment program. 
Scientific Review:
Despite the efficacy of many evidence-based treatments for psychiatric disorders, a large 
percentage of treatment completers maintain their diagnosis and symptoms after treatment (e.g., 
Nemeroff, 2012; Schottenbauer et al., 2008; Larsen et al., 2019). For veterans with PTSD, 
approximately 66% of all individuals who successfully complete an evidence-based treatment 
retain their PTSD diagnosis (Steenkamp et al., 2015). 
An intervention that has been shown to be effective for non-response to first-line 
psychotherapies is transcranial magnetic stimulation (TMS). TMS is a safe, noninvasive 
intervention that uses a magnetic field to modulate cortical activity in brain areas linked to an 
overactive stress response. When compared to sham conditions which resemble the TMS 
condition but do not utilize any magnetic fields (i.e., proposed active ingredient), TMS has been 
associated with reduced depressive symptoms in treatment non-responders (e.g., Somani & Kar, 
2019). Although the bulk of research examines TMS as a treatment for major depressive 
disorder, TMS has also shown promise in reducing symptoms of other psychiatric disorders such 
as PTSD (Kan et al., 2020). 
In prior research TMS was associated with medium to large reductions in core PTSD symptoms 
when compared to sham conditions. Symptom reductions achieved via TMS have been 
ORA: 21110503-IRB01   Date IRB Approved: 11/18/2024   Amendment Date: 3/7/2025

demonstrated to persist (Kan et al., 2020). A recent study compared Cognitive Processing 
Therapy (CPT) combined with TMS to CPT with a sham condition and found that CPT 
combined with TMS was associated with greater PTSD symptom reductions during treatment 
and at six-month follow-up than CPT combined with a sham condition (Kozel et al., 2018). This 
finding suggests that TMS may be beneficial as an augmentation to CPT. However, to our 
knowledge, previous literature has not yet examined whether TMS improves outcomes for 
individuals who are likely to not respond to CPT treatment. 
Due to the demand for briefer TMS protocols, theta burst stimulation (iTBS) is a variation on 
TMS. Studies have found iTBS to be more efficient than standard TMS but still associated with 
significant improvements and low side effects in both depression and PTSD (Philip et.al., 2019; 
Chu, et. al., 2020). The present study will utilize the more efficient iTBS protocol applied to the 
right dorsolateral prefrontal cortex (DLPFC) in order to reduce the length of stay for the 
participants.
Roughly one in four participants who complete Cognitive Processing Therapy (CPT) in the 2-
week intensive outpatient program (IOP) at the Road Home Program at Rush do not report a 
meaningful reduction in PTSD symptoms and can be classified as non-responders. The present 
study seeks to determine whether adding iTBS to standard IOP programming reduces PTSD 
symptoms among participants who have not reported reduced symptoms by the end of the first 
week of treatment (i.e., likely non-responders). 
Research Plan: 
We plan to evaluate the incremental impact adding iTBS to the IOP has on overall PTSD and 
depression symptom reductions among likely non-responders. Using our established machine 
learning algorithms, we plan to identify individuals who are predicted to be likely non-
responders by the end of the first IOP week. Identified individuals will then be offered to 
participate in a study on PTSD and iTBS for the remainder of their treatment (last six days of the 
IOP). Interested individuals will be consented by study staff . On the Friday of the first week and 
throughout the second week of the IOP, individuals receive a dose of  TMS prior to each of their 
two CPT sessions per day.
To better evaluate the results of TMS, we will do propensity score matching using demographic 
(i.e., gender, age) and clinical characteristics (i.e., PCL-5 at intake and IOP Day 5). This data 
will be pulled from the Road Home Data Repository (ORA#14011508) for analysis.  
Inclusion and Exclusion Criteria:
Inclusion Criteria: 

Veterans or service members between the ages of 18 and 65 who are attending the 2-
week Intensive Outpatient Program at the Road Home Program and have not had 
significant PTSD symptom change based on the PCL-5 during the first week of 
treatment.

Participants with an HDRS-21 score ≤ 26 at screening visit

Negative pregnancy test in women of childbearing age
ORA: 21110503-IRB01   Date IRB Approved: 11/18/2024   Amendment Date: 3/7/2025


Subject is able to adhere to the treatment schedule
Exclusion Criteria: 

Individuals with implants and non-removable metals which prevent them from safely 
receiving TMS, including:
o
Aneurysm clips or coils
o
Stents in the head, neck, or brain
o
Deep brain stimulators
o
Metallic implants in the head, neck, or brain (braces and dental implants do not 
interfere and are safe for TMS)
o
Shrapnel or bullet fragments in or near the head
o
Facial tattoos with metallic or magnetic-sensitive ink
o
Other metal devices or ferromagnetic objects implanted in or near the head
o
Pacemakers, intra-cardiac lines, or implanted medical pumps

Individuals with a history of seizures or epilepsy (except those therapeutically induced by 
ECT)

Individuals diagnosed with major, chronic mental health illnesses such as Psychotic 
Disorders, Bipolar Disorders, and Obsessive Compulsive Disorder

Individuals with a history of substance abuse within the past six months

Individuals with a history of significant head trauma with a loss of consciousness for 
longer than 5 minutes

Individuals with severe or frequent headaches

Individuals with significant hearing loss

Individuals with significant neurological disorders such as Parkinson’s disease, 
Huntington’s chorea, and Multiple sclerosis

Individuals with unstable physical disease, such as unstable cardiac diseases

Individuals currently on Benzodiazepine at a dose higher than 3mg or Lorazepam or 
equivalent.

Women who are breastfeeding

Individuals with previous TMS treatment
Study Population: 
We plan to enroll a total of 15 likely non-responders  and will evaluate PTSD and depression 
symptom reductions from pre-to post-treatment and pre- to 1- and 3-month follow-ups. 
Study Activities:
Screening/Baseline Assessment:
On day 5 of IOP treatment, participants who have not had significant PTSD symptom change 
based on the PCL-5 will be approached to participate in the study. 
Acute Treatment Phase:
The present study uses the FDA cleared NeuroStar TMS Therapy System. Participants will 
receive two iTBS treatments daily for 5 days. At each iTBS session the study personnel will 
collect and record any adverse events reported. 
ORA: 21110503-IRB01   Date IRB Approved: 11/18/2024   Amendment Date: 3/7/2025

Prior to the initiation of iTBS on the first day, each participant’s motor threshold (MT) will be 
established with an active coil. The MT will be determined by the stimulator output sufficient to 
induce movement in the contralateral hand >50% of the time.
Treatment Parameters:
o
Total Number of pulses: 1800
o
Orientation: right dorsolateral prefrontal cortex (DLPFC)
o
Pulses: 3
o
Interpulse interval: 20 seconds
o
Bursts per second: 5
o
Stimulation time: 2 seconds
o
Interval: 10 seconds
o
Intensity: 90% active motor threshold
o
Total treatment time: 12 minutes
1- and 3-Month Follow-Ups:
Participants will be contacted to complete assessments.
Measures: 
Study participants will complete the same validated measures as individuals enrolled in the Road 
Home Program IOP at treatment endpoint and at the 1- and 3-month follow-up timepoints. In 
addition to these measures completed by all IOP participants, participants in this study will 
complete the  HAM-D to measure  depressive symptoms, respectively, at the time of enrollment 
on Friday of the first week of treatment, 1-month follow-up, and at 3-month follow-up. 
Measure
Focus
Timing
PTSD Checklist for 
DSM-5
PTSD Symptoms
IOP Baseline*, 
Endpoint*, 1-month*, 
3-month*
Patient Health 
Questionnaire
Depression 
Symptoms
IOP Baseline*, 
Endpoint*, 1-month*, 
3-month*
Hamilton Depression 
Rating Scale 
Depression 
Symptoms
End of first week, 1-
month, 3-month
PROMIS SF8a
Satisfaction with 
Social Roles and 
Functioning
IOP Baseline*, 
Endpoint*, 3-month*
Veteran RAND-12
Mental and physical 
functioning
IOP Baseline*, 3-
month*
Neurobehavioral 
Symptom Inventory
Neurobehavioral 
symptoms
IOP Baseline*, 
Endpoint*
* Part of the standard Road Home Program IOP assessment schedule. 
ORA: 21110503-IRB01   Date IRB Approved: 11/18/2024   Amendment Date: 3/7/2025

 
 
 
Risks: 
TMS is well-tolerated and associated with few side-effects. The most common side-effect, which 
is reported in less than half of individuals, is mild headache. Some individuals report feeling 
sensations on the scalp or facial twitching which should not be painful or and should diminish 
rapidly. Due to the noise the TMS machine produces, earplugs are given to individuals to 
mitigate any discomfort. The most serious risk of TMS is seizures, however, the risk of 
experiencing a seizure during TMS is exceedingly low. Qualified medical staff will be present 
during the TMS administration and would be able to intervene immediately and ensure patient 
safety in the event of an adverse event. Qualified medical staff is also present during business 
hours as part of the Road Home Program IOP. Participants will be advised to call 911 or go to 
their nearest emergency room in case of emergencies.
Describe the procedures that will be in place to minimize any risks:  
Prior to beginning TMS treatments, a medical history asking about possible implants or other 
metals in the body will be completed. Participants will be thoroughly screened for any magnetic-
sensitive objects prior to each treatment session. Participants will be asked to remove any 
magnetic-sensitive objects from their person (e.g., jewelry, credit cards). Participants will be 
given earplugs during treatment for their comfort and hearing protection. TMS treatments will be 
administered and supervised by qualified medical staff trained in TMS. The participant can stop 
treatment at any time. Qualified medical staff will be present during the TMS administration and 
would be able to intervene immediately and ensure patient safety in the event of an adverse 
event. Qualified medical staff is also present during business hours as part of the Road Home 
Program IOP. Participants will be advised to call 911 or go to their nearest emergency room in 
case of emergencies.
To minimize the risk of loss of confidentiality, all study staff will work very hard to ensure that 
all data is stored securely so that only members of the study staff will have access to identifiable 
data. No identifiable data will ever be disclosed to any outside parties. Participants' identities will 
not be revealed on any report, publication, or at scientific meetings.
Benefits: 
Participants may experience direct benefits as a result of participating in this study. If iTBS is 
effective at improving outcomes for likely non-responders, as hypothesized, these individuals 
may experience meaningful PTSD and depression symptom reductions.  
Assuming the proposed project is successful and veterans who are likely non-responders report 
substantially larger PTSD and depression symptom reductions following TMS compared to no 
additional intervention, iTBS could become part of the routine clinical programming that is 
offered to likely non-responders. As a result, overall program outcomes, including satisfaction, 
should further improve.
If successful, the proposed project may also have broader implications for the future of IOP 
programming. Whereas IOP programming is currently relatively static, the successful project 
would suggest that modifying and personalizing the care veterans receive based on their 
observed treatment response can further improve care. As such, this project would lay the 
ORA: 21110503-IRB01   Date IRB Approved: 11/18/2024   Amendment Date: 3/7/2025

foundation for future studies that examine various program modification that can help tailor 
treatment to each warrior based on their symptoms prior to and during treatment.
Informed Consent:
Informed consent will be obtained prior to any study procedures. Potential participants will be 
informed that their decision about participation will in no way affect the care that they receive at 
the Road Home Program or at RUMC.
Are you applying for a waiver of consent or assent? (Waiver of consent implies you will not 
obtain written or signed consent.)
No.
Will a Certificate of Confidentiality be obtained for this study?
No.
Data Storage:
Specify the site at which the data will be stored and how it will be stored:
Sources of data that will be included in this study are captured in the IRB-approved data 
repository (ORA# 14011508). All survey data are collected using online surveys (REDCap), 
which are regularly used for Department of Psychiatry procedures. All electronic data that is 
collected through self-reported questionnaires will be password protected and stored on the 
RUMC secure server. A request for de-identified data will be submitted to Sarah Pridgen, the 
data repository manager, who will manage all access to data from the data repository. Only 
individuals that have been IRB approved will have access to any data collected. The information 
that is collected in this study will not be disclosed to any outside parties. All the findings in this 
study will be reported at a group level will no risk of identifying individual participants.
Given the clinical nature of this study, study participants’ MRN will be obtained to link their 
study data to their Electronic Medical Record in Epic, REDCap, and any data that is stored on 
the secure Rush network server. Medical record data will be stored in Epic in accordance with 
RUMC policy. 
How long will the data be maintained and/or stored?
This project will examine whether ITBS can aid veterans at risk of treatment non-response. 
Results will be evaluated, in part, via the same measures given as part of the routine care in the 
Road Home Program IOP. Because much of the outcome data is connected to routine care, all 
study-related data will be maintained and stored securely indefinitely.
Who, other than the specified study team, will have access to the study records or data? 
Specify their name, role, and affiliation.
No one outside of the specified study team will have access to the study data or records. 
If coded or identified data will be released, specify the persons/agencies to whom the 
information will be released. Please also indicate the provisions that will be taken to assure 
that the transmission of the data will maintain confidentiality:
ORA: 21110503-IRB01   Date IRB Approved: 11/18/2024   Amendment Date: 3/7/2025

Results from analyses of group level limited use datasets may be presented in grants, 
manuscripts, or professional presentation in the future.
Describe what will happen to the data or dataset (including photographs and/or 
audio/video recordings) when the study is completed. Please indicate your plans for the 
destruction of identifiers at the earliest opportunity consistent with the conduct of the 
research and/or clinical needs, if applicable:
Because much of the outcome data is connected to routine care (ORA# 14011508), all study-
related data will be maintained and stored securely indefinitely.
What process will be in place to assure that all investigators seeking access to the data bank 
have received IRB approval or exemption for their studies?
The individuals listed on this IRB or first approved in the future specifically on this IRB protocol 
will have access to the data set for research activities. In addition, individuals who obtain IRB 
approval to use the data set established by this study will be given access to a de-identified data 
set containing only the approved variables of interest following a formal request for a data set 
submitted to the principal investigator. All such research activities will be conducted with a de- 
identified data set and will be reported at the group level with no risk of identifying individual 
patients.
Justify your needs to collect PHI in this study:
PHI will be collected to access Epic and REDCap in order to characterize the participant sample. 
Treatment dates are collected as part of routine clinical care to document treatment progress. 
Describe how and where PHI will be destroyed following the completion of the study: 
Not applicable. PHI exists in Epic and REDCap or in a restricted folder on the RUMC secure 
server; data will remain here secure and indefinitely. No identifiable data will ever be shared 
with personnel outside of the approved study staff. 
Will subjects be able to request that their information be removed from the data bank?
No.
If no, please explain why not: 
The data collected are necessary clinic procedures that are conducted to ensure proper care. As is 
true with all clinical care, patients have the right to refuse care procedures. Thus, patients could 
refuse to complete the questionnaires which are used to determine PTSD symptom severity. 
However, once the questionnaires have been collected, these data become part of the patient’s 
clinical record and cannot be removed. 
Costs: 
There will be no cost to participants to participate in this study.
Compensation: 
ORA: 21110503-IRB01   Date IRB Approved: 11/18/2024   Amendment Date: 3/7/2025

Participants will be compensated for their time if they complete the additional surveys: $20 at the 
end of the first week of treatment, $20 for 1-month post-treatment, and $40 for 3-month follow-
up surveys. 
ORA: 21110503-IRB01   Date IRB Approved: 11/18/2024   Amendment Date: 3/7/2025