Personalized TMS-fNIRS for PTSD

Overseen By Kevin Johnson, PhD, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Florida State University

Must not be taking: Tricyclics, Clozapine

Disqualifiers: Schizophrenia, Substance use, Severe TBI, 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: Unknown

Duration: 30 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new technology called TMS-fNIRS (Transcranial Magnetic Stimulation combined with Functional Near-Infrared Spectroscopy) to better understand and treat PTSD (post-traumatic stress disorder). The researchers aim to determine if this technology can more accurately measure brain activity and improve the dosing of TMS (transcranial magnetic stimulation) therapy. Participants will receive either real or sham (inactive) stimulation to test the technology's effectiveness. Suitable candidates have a PTSD diagnosis and have remained stable on any medication or therapy for at least a month. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could enhance PTSD treatment options.

Will I have to stop taking my current medications?

The trial requires that you do not change your psychotropic medications (medications affecting mood, perception, or behavior) for at least one month before starting and throughout the study. If you are taking medications that significantly lower the seizure threshold, you may not be eligible to participate.

What prior data suggests that this TMS-fNIRS technology is safe for PTSD patients?

Research shows that TMS (transcranial magnetic stimulation) is generally well-tolerated by patients. Studies have found that TMS can safely treat conditions like PTSD and depression. Most side effects are mild and temporary, such as slight headaches or scalp discomfort, and they usually resolve soon after treatment.

Adding fNIRS (functional near-infrared spectroscopy) to TMS aims to enhance precision by directly measuring brain activity. This could help ensure the correct amount of TMS is administered, reducing the risk of incorrect dosing. While specific data on TMS-fNIRS is limited, the technology's components have been used safely before.

Overall, early findings suggest that TMS-fNIRS is a promising and safe method for guiding therapy in PTSD and other conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the TMS-fNIRS technique for treating PTSD because it combines two innovative technologies: Transcranial Magnetic Stimulation (TMS) and functional Near-Infrared Spectroscopy (fNIRS). Unlike traditional treatments like medication and talk therapy, TMS-fNIRS targets the brain's dl-PFC area to directly modulate neural activity. This non-invasive method not only aims to provide more immediate relief from PTSD symptoms but also offers real-time monitoring of brain responses, which could lead to more personalized and effective treatment plans. By integrating these advanced technologies, there's hope for a faster and more precise approach to managing PTSD.

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

Research has shown that transcranial magnetic stimulation (TMS) can improve symptoms of depression and anxiety, which are common in PTSD. Studies have also found TMS to be important for treating mental health issues like PTSD. In this trial, participants will receive either active or sham TMS-fNIRS over the dl-PFC. Adding functional near-infrared spectroscopy (fNIRS) may help track changes in brain activity during TMS treatment. Early findings suggest that fNIRS can detect physical changes that occur with TMS therapy. This combination, TMS-fNIRS, aims to offer more personalized treatment, potentially improving outcomes for those with PTSD. ^{1 2 3 4 6}

Who Is on the Research Team?

Frank A Kozel, M.D., M.S.C.R., D.F.A.P.A.

Principal Investigator

Florida State University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-70 with PTSD, who may also have mild TBI. Participants must be eligible for TMS treatment, diagnosed with PTSD using CAPS-5, and on a stable psychotropic medication or psychotherapy regimen for at least one month prior to the study.

Inclusion Criteria

Diagnosis of PTSD based on CAPS-5

I am considered a candidate for TMS therapy for my PTSD.

I understand the study details and can follow its requirements.

Exclusion Criteria

OCD cannot be the primary disorder but can have OCD symptoms

Current, planned, or suspected pregnancy

Suicidal risk that precludes safe participation defined as clinical impression that the participant is at significant risk for suicide

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive TMS-fNIRS therapy, randomized to active or sham stimulation of the dl-PFC, with four different TMS-fNIRS protocols

30 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TMS-fNIRS

Trial Overview The study tests personalized TMS-fNIRS technology as a potential replacement for indirect motor threshold procedures in dosing TMS. It aims to directly measure frontal brain activity in patients with depression, PTSD, or TBI.

How Is the Trial Designed?

Group I: TMS-fNIRS over the dl-PFC (Active) Active Control 1 Intervention

TMS-fNIRS dl-PFC data will be acquired with participants being randomized to active or sham stimulation of the dl-PFC, with the randomizing of the order of four different TMS-fNIRS protocols.

Group II: TMS-fNIRS over the dl-PFC (Sham) Placebo Group 1 Intervention

TMS-fNIRS dl-PFC data will be acquired with participants being randomized to active or sham stimulation of the dl-PFC, with the randomizing of the order of four different TMS-fNIRS protocols.

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

Approved in United States as TMS for:

• Major Depressive Disorder
• Post-Traumatic Stress Disorder (PTSD)
• Traumatic Brain Injury (TBI)

Approved in European Union as rTMS for:

• Major Depressive Disorder
• Chronic Pain
• Post-Traumatic Stress Disorder (PTSD)
• Traumatic Brain Injury (TBI)

Approved in Canada as TMS for:

• Major Depressive Disorder
• Chronic Pain
• Post-Traumatic Stress Disorder (PTSD)
• Traumatic Brain Injury (TBI)

Who Is Running the Clinical Trial?

Florida State University

Lead Sponsor

Trials

234

Recruited

41,100+

Published Research Related to This Trial

The study confirms that the combined use of repetitive transcranial magnetic stimulation (rTMS) and functional near-infrared spectroscopy (fNIRS) can reliably measure brain responses, showing moderate-to-high reliability in oxygenated hemoglobin concentration changes across groups.

The spatial patterns of brain activity measured by this method are highly reproducible, indicating that this combined approach could be a valuable clinical tool for assessing rTMS effects on brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Test-retest assessment of cortical activation induced by repetitive transcranial magnetic stimulation with brain atlas-guided optical topography. Tian, F., Kozel, FA., Yennu, A., et al.[2019]

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 11 healthy subjects, low-frequency rTMS applied to the right frontal lobe led to significant changes in oxygenated hemoglobin levels in the left frontal lobe, indicating both deactivation during stimulation and subsequent activation afterward.

These results suggest that rTMS can effectively modulate brain activity, and if confirmed in depressed patients, near-infrared spectroscopy (NIRS) could be a useful tool for monitoring the effects of rTMS and tailoring treatment for individuals.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deactivation and activation of left frontal lobe during and after low-frequency repetitive transcranial magnetic stimulation over right prefrontal cortex: a near-infrared spectroscopy study. Hanaoka, N., Aoyama, Y., Kameyama, M., et al.[2007]

The combination of Transcranial Magnetic Stimulation (TMS) and functional Near-Infrared Spectroscopy (fNIRS) has been explored in 53 studies, showing that TMS can significantly affect cortical hemodynamic measures, particularly in the dorsolateral prefrontal cortex (DLPFC) and motor cortex (M1), with 21 out of 22 studies reporting significant changes in oxygenated hemoglobin levels ([HbO]).

While TMS+fNIRS shows promise for assessing cortical excitability and brain activity, the review highlights the need for more controlled studies due to the variability in methodologies and a lack of replicated findings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Review of Integrated Functional Near-Infrared Spectroscopy (fNIRS) and Transcranial Magnetic Stimulation (TMS) Studies. Curtin, A., Tong, S., Sun, J., et al.[2020]

In a study of 770 veterans with major depressive disorder (MDD), TMS treatment led to significant reductions in both MDD and PTSD symptoms, with a response rate of 41.4% and remission rate of 20% for MDD after receiving an adequate dose of 30 sessions.

The treatment was found to be safe, with side effects aligning with the known safety profile of TMS, and 65.3% of veterans with comorbid PTSD experienced clinically meaningful symptom reductions, indicating TMS's effectiveness in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prefrontal transcranial magnetic stimulation for depression in US military veterans - A naturalistic cohort study in the veterans health administration. Madore, MR., Kozel, FA., Williams, LM., et al.[2023]

Transcranial magnetic stimulation (TMS) is a promising noninvasive treatment for PTSD, showing safety and efficacy in numerous studies, including nine randomized controlled trials and various prospective studies.

While TMS has demonstrated positive outcomes for PTSD, there is a need for more standardized approaches and long-term studies to better understand treatment duration and optimize patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for post-traumatic stress disorder. Petrosino, NJ., Cosmo, C., Berlow, YA., et al.[2022]

The study involved 11 healthy participants and demonstrated that simultaneous functional Near Infrared Spectroscopy (fNIRS) and repetitive Transcranial Magnetic Stimulation (rTMS) can effectively measure brain activation and connectivity, particularly in the motor and prefrontal cortices.

Stimulation of these brain regions led to a significant decrease in oxygenated hemoglobin levels in both the stimulated and opposite cortices, indicating reliable cortical responses that could aid in understanding brain disorders and the effects of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Using simultaneous repetitive Transcranial Magnetic Stimulation/functional Near Infrared Spectroscopy (rTMS/fNIRS) to measure brain activation and connectivity. Kozel, FA., Tian, F., Dhamne, S., et al.[2023]

A study involving 17 healthy participants demonstrated that a continuous-wave LED-based functional near-infrared spectroscopy (fNIRS) system can effectively measure changes in blood flow in the dorsolateral prefrontal cortex (DLPFC) during transcranial magnetic stimulation (TMS).

High-frequency TMS stimulation resulted in a significantly larger response in cortical activity compared to other stimulation types, suggesting that this method can enhance the evaluation of TMS therapies and their effects on brain function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of evoked responses to pulse-matched high frequency and intermittent theta burst transcranial magnetic stimulation using simultaneous functional near-infrared spectroscopy. Curtin, A., Sun, J., Ayaz, H., et al.[2020]

In a study of 29 individuals with comorbid major depressive disorder (MDD) and posttraumatic stress disorder (PTSD), machine learning analysis of EEG coherence was able to predict clinical outcomes after TMS treatment, with a high area under the curve of 0.83 for MDD and 0.71 for PTSD.

The study demonstrated that EEG coherence could effectively differentiate between pre- and post-TMS treatment states, achieving an accuracy of around 75-78% across different brain wave frequencies, suggesting potential for EEG as a screening tool for TMS candidates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of machine learning in predicting clinical response to transcranial magnetic stimulation in comorbid posttraumatic stress disorder and major depression: A resting state electroencephalography study. Zandvakili, A., Philip, NS., Jones, SR., et al.[2021]

In a study of 12 patients with both PTSD and major depression, 75% experienced a significant improvement in depression symptoms after receiving repetitive transcranial magnetic stimulation (rTMS) over 10 days.

While rTMS showed effectiveness in alleviating depression and related symptoms like anxiety and insomnia, it had only minimal impact on the core symptoms of PTSD, suggesting that different treatment approaches may be needed for mood and PTSD symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression. Rosenberg, PB., Mehndiratta, RB., Mehndiratta, YP., et al.[2006]

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]

Citations

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Title: TMS-fNIRS Personalized Dosing NCT Number TMS is a promising potential therapy for PTSD, and the technology developed in this project will help advance research and clinical practice for. PTSD, ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12129770/

Status and trends in transcranial magnetic stimulation research Studies have shown that TMS plays an important role in some psychiatry diseases, such as depression, post-traumatic stress disorder (PTSD), and ...

3. withpower.com withpower.com/trial/phase-brain-injuries-8-2023-1476e

Personalized TMS-fNIRS for PTSD Research shows that repetitive transcranial magnetic stimulation (rTMS) can improve symptoms of depression and anxiety, which are often present in PTSD, though ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6518445/

Using Functional Near-Infrared Spectroscopy to Study the ... This case study suggests fNIRS may be sensitive to physiological changes that accompany rTMS treatment.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04568369

Treatment of Post-concussion Syndrome With TMS: Using ... The primary objective of this study is to determine whether rTMS treatment can significantly improve persistent post-concussion symptoms.

6. frontiersin.org frontiersin.org/journals/neurology/articles/10.3389/fneur.2019.00476/full

Using Functional Near-Infrared Spectroscopy to Study the ... This case study suggests fNIRS may be sensitive to physiological changes that accompany rTMS treatment.