TMS for Post-Traumatic Stress Disorder

Overseen By Allyson C Rosen, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Allyson Rosen

Must not be taking: Seizure risk, Hemodynamic influencers

Disqualifiers: Significant dementia, Urgent care need, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat post-traumatic stress disorder (PTSD) using transcranial magnetic stimulation (TMS) combined with brain imaging (fMRI). The researchers aim to observe changes in brain activity with this treatment, potentially paving the way for personalized therapy for PTSD in the future. Participants will undergo psychological tests and brain scans and receive TMS at various brain locations. Individuals diagnosed with PTSD who can tolerate MRI and TMS procedures make excellent candidates for this study. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to innovative PTSD treatments.

Do I have to stop taking my current medications for the trial?

The trial requires you to maintain a stable medication regimen between the two fMRI sessions. However, if you are currently taking medications that increase the risk of seizure or influence hemodynamic response, you may be excluded from participating.

What prior data suggests that this TMS-fMRI technique is safe for PTSD patients?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) is generally a safe treatment. It is non-invasive, meaning it doesn't involve surgery or entering the body. Studies have found that the FDA has already approved rTMS for treating depression that doesn't respond to other treatments. This approval suggests it might also be safe for other conditions like PTSD, although more research is needed.

Reports indicate that rTMS might not always improve PTSD symptoms immediately after treatment. However, it doesn't seem to have serious safety issues. Some people might experience mild side effects like headaches or feeling light-headed, but these usually resolve quickly.

Overall, rTMS appears promising for treating PTSD and has a good safety record. This study aims to examine how rTMS affects the brain in people with PTSD, which could help improve future treatments. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about TMS-fMRI for treating Post-Traumatic Stress Disorder (PTSD) because it combines transcranial magnetic stimulation (TMS) with functional magnetic resonance imaging (fMRI) to precisely target brain regions involved in PTSD. Unlike traditional treatments like psychotherapy or medication, which can take weeks to show effects, TMS-fMRI offers the potential for more immediate and focused intervention. This method allows for real-time monitoring of brain activity, enabling researchers to understand the precise impact of TMS on brain function and potentially leading to more personalized and effective treatments for PTSD.

What evidence suggests that TMS-fMRI is effective for PTSD?

Studies have shown that repetitive transcranial magnetic stimulation (rTMS) might alleviate PTSD symptoms. Research suggests that rTMS targets specific brain areas, potentially reducing anxiety and unwanted memories associated with PTSD. Although rTMS is already approved for depression treatment, its potential for PTSD generates excitement. Early findings indicate that rTMS could alter brain activity in ways that might lessen PTSD symptoms. More research is needed to fully understand its effects on PTSD, but the potential is promising. Participants in this trial will undergo TMS-fMRI, which combines TMS and fMRI to explore its effects on PTSD. ^{2 6 7 8 9}

Who Is on the Research Team?

Allyson C Rosen, Ph.D.

Principal Investigator

PAVIR/Palo Alto VAHCS/Stanford University

Are You a Good Fit for This Trial?

This trial is for individuals aged 18-55 with PTSD, who can safely undergo MRI and TMS procedures. Participants must be able to understand and sign the consent form, have a confirmed PTSD diagnosis per DSM 5 criteria, and commit to not changing their medication between two fMRI sessions.

Inclusion Criteria

Able to read, verbalize, understand, and voluntarily sign the Informed Consent Form prior to participating in any study-specific procedures or assessments

Commitment to maintaining a stable medication regimen between the two fMRI sessions

I can safely have an MRI and TMS without discomfort.

Exclusion Criteria

Presence of any other condition that has the potential to prevent study completion and/or have a confounding effect on the interpretation of results

Being in urgent need of care that would make participation impossible

Inability to safely and comfortably undergo an MRI. MRI safety will be determined by the center where MRI's are collected

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 visit

1 visit (in-person)

Baseline Assessment

Participants undergo MRI, psychological, and functional testing to characterize them and confirm eligibility

1 visit

1 visit (in-person)

TMS-fMRI Sessions

Participants undergo simultaneous TMS-fMRI and cTBS and fMRI in two separate sessions

2 visits

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TMS-fMRI

Trial Overview The study tests whether targeting a new brain area with repetitive pulse transcranial magnetic stimulation (rTMS) while using functional magnetic resonance imaging (fMRI) can help manage PTSD symptoms by altering brain activity. It aims at personalizing rTMS treatment based on brain imaging.

How Is the Trial Designed?

Group I: TMS-fMRI Experimental Treatment 1 Intervention

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.

TMS-fMRI is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder
• Migraines

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive-Compulsive Disorder

Who Is Running the Clinical Trial?

Allyson Rosen

Lead Sponsor

Trials

1

Recruited

30+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Patients with PTSD following minor head trauma showed significantly lower motor evoked potential (MEP) inhibition compared to healthy controls, indicating abnormal motor cortex excitability.

The study, involving 14 PTSD patients and 23 healthy subjects, suggests that PTSD may lead to changes in intracortical inhibition, which could be linked to neuroticism and other psychological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cortical hyperexcitability in post-traumatic stress disorder secondary to minor accidental head trauma: a neurophysiologic study. Centonze, D., Palmieri, MG., Boffa, L., et al.[2018]

In a study of 20 drug-naive PTSD patients and 16 healthy controls, PTSD patients exhibited significant impairments in GABA(A)-ergic function, particularly in the right hemisphere, indicating a potential imbalance in neurotransmitter systems related to their symptoms.

The findings suggest that the altered cortical excitability in PTSD patients, characterized by increased glutamatergic activity and decreased GABA(A)-ergic function, could inform new treatment strategies using neuromodulation techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dysfunctions of cortical excitability in drug-naïve posttraumatic stress disorder patients. Rossi, S., De Capua, A., Tavanti, M., et al.[2021]

In a study of 33 adults with comorbid major depressive disorder and posttraumatic stress disorder, TMS therapy was shown to alter brain connectivity, particularly between the subgenual anterior cingulate cortex and the default mode network, which predicted clinical improvement.

After TMS treatment, reductions in connectivity between specific brain regions were associated with symptom relief, suggesting that these connectivity changes may serve as biomarkers for treatment response in patients with these disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder. Philip, NS., Barredo, J., van 't Wout-Frank, M., et al.[2020]

In a study involving 18 patients with PTSD, low-frequency repetitive transcranial magnetic stimulation (rTMS) to the right prefrontal cortex significantly improved overall PTSD symptoms, particularly in re-experiencing and total scores on the Clinician-Administered PTSD Scale (CAPS).

The results suggest that rTMS is a safe and effective treatment option for PTSD, with a notable impact on specific symptom clusters, indicating potential for further research into optimizing rTMS protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-frequency, Repetitive Transcranial Magnetic Stimulation for the Treatment of Patients with Posttraumatic Stress Disorder: a Double-blind, Sham-controlled Study. Nam, DH., Pae, CU., Chae, JH.[2021]

In a study involving 24 PTSD patients, high-frequency repetitive transcranial magnetic stimulation (rTMS) at 10 Hz significantly improved core PTSD symptoms and alleviated anxiety over 10 daily sessions.

The results indicate that rTMS targeting the right dorsolateral prefrontal cortex is more effective than low-frequency or sham stimulation, suggesting its potential as a therapeutic intervention for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of the right dorsolateral prefrontal cortex in posttraumatic stress disorder: a double-blind, placebo-controlled study. Cohen, H., Kaplan, Z., Kotler, M., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

In a study of 20 male combat veterans with treatment-resistant PTSD, repetitive transcranial magnetic stimulation (rTMS) significantly reduced hyperarousal symptoms, suggesting its potential effectiveness for this specific symptom.

However, rTMS did not show significant improvements in overall PTSD symptoms or co-occurring depression and anxiety scores, indicating that while it may help with hyperarousal, further research is needed to understand its broader efficacy in PTSD treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is transcranial magnetic stimulation effective in treatment-resistant combat related posttraumatic stress disorder? Oznur, T., Akarsu, S., Celik, C., et al.[2014]

In a study involving 30 patients with PTSD, both left and right dorsolateral prefrontal cortex (DLPFC) stimulation using 20 Hz rTMS significantly reduced PTSD symptoms, with right DLPFC stimulation showing a larger effect.

The treatment was safe, with no cognitive worsening observed, and the benefits lasted for at least three months after the treatment, suggesting that rTMS could be an effective long-term intervention for PTSD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive brain stimulation with high-frequency and low-intensity repetitive transcranial magnetic stimulation treatment for posttraumatic stress disorder. Boggio, PS., Rocha, M., Oliveira, MO., et al.[2021]

In a study involving 429 pediatric patients undergoing transcranial magnetic stimulation (TMS) for motor and language mapping, most adverse events were benign, with seizures occurring in 5.8% of sessions but not conclusively linked to TMS.

TMS was safely performed in patients with cranial metal, and useful mapping results were achieved in nearly all cases, indicating that TMS is a safe option for functional mapping in pediatric patients with epilepsy or brain tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-guided TMS is safe in a predominately pediatric clinical population. Braden, AA., Weatherspoon, SE., Boardman, T., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9193572/

Transcranial Magnetic Stimulation for Post-traumatic Stress ... Overall, TMS is a relatively safe treatment. Currently, the only FDA- approved to treat refractory depression, but with the potential to treat many other ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12452984/

The Effects of Repetitive Transcranial Magnetic Stimulation on ... One-year clinical outcomes following theta burst stimulation for post-traumatic stress disorder. Neuropsychopharmacology. 2020;45(6):940–946 ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S016503272100327X

Transcranial magnetic stimulation as a treatment for ... TMS shows potential as a treatment for PTSD, although further research is required to understand the neurological mechanisms of TMS on specific PTSD symptoms.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT02981381

Synchronized Transcranial Magnetic Stimulation for PTSD It is hypothesized that sTMS will be effective for PTSD and mood symptoms. Detailed Description. Posttraumatic stress disorder (PTSD) is a highly prevalent ...

5. nature.com nature.com/articles/s41398-020-0851-5

Non-invasive brain stimulation for posttraumatic stress ... Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) hold promise for the treatment of posttraumatic stress ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39092744/

Repetitive transcranial magnetic stimulation for post- ... Our review suggests that active rTMS probably makes little to no difference to PTSD severity immediately following treatment compared to sham stimulation.

7. sciencedirect.com sciencedirect.com/science/article/pii/S109471592201399X

Repetitive Transcranial Magnetic Stimulation for ... Veterans with mTBI had greater PTSD symptoms, yet neither TBI status nor cumulative head injuries reduced TMS effectiveness.

8. clinicaltrials.gov clinicaltrials.gov/study/NCT05512143?term=AREA%5BConditionSearch%5D(PTSD)%20AND%20AREA%5BInterventionSearch%5D(TMS)%20AND%20SEARCH%5BLocation%5D(AREA%5BLocationCountry%5DUnited%20States)&rank=3

NCT05512143 | TMS for PTSD and Blood Pressure Repetitive transcranial magnetic stimulation (TMS) is a safe, non-invasive, promising novel approach to treat PTSD and reduce risk for CVD. TMS dramatically ...

9. mdpi.com mdpi.com/2076-3425/13/9/1274

Repetitive Transcranial Magnetic Stimulation (rTMS) in ... If this additional therapy is successful, it may strengthen the case for regulatory authorities to approve this additional technique of treating PTSD.