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?

The intent of this study is to establish technical feasibility in a clinical population (PTSD, with or without mild TBI) of personalized TMS-fNIRS technology. Thereby demonstrating the utility of transcranial magnetic stimulation - functional near-infrared spectroscopy (TMS-fNIRS) technology as a direct measure of frontal brain activity, potentially replacing the indirect motor threshold procedure that may lead to improper dosing of TMS. Personalized TMS-fNIRS technology will guide therapy for depression, post-traumatic stress disorder (PTSD), and/or traumatic brain injury (TBI)

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.

Is TMS-fNIRS safe for humans?

Transcranial Magnetic Stimulation (TMS) has been used for many years as a noninvasive treatment for psychiatric conditions like depression and PTSD, and it is generally considered safe and well-tolerated in humans. ^{1 2 3 4 5}

How is the TMS-fNIRS treatment for PTSD different from other treatments?

The TMS-fNIRS treatment for PTSD is unique because it combines transcranial magnetic stimulation (TMS), which uses magnetic pulses to stimulate brain activity, with functional near-infrared spectroscopy (fNIRS), a noninvasive imaging technique that measures brain activity by detecting changes in blood flow. This combination allows for real-time monitoring of brain responses during treatment, potentially offering more precise and personalized therapy compared to traditional methods. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment 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 it may not significantly improve core PTSD symptoms. Additionally, combining TMS with functional near-infrared spectroscopy (fNIRS) can help measure brain responses, potentially enhancing the understanding and effectiveness of the treatment. ^{3 6 8 10 11}

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

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 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 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]

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 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]

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 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]

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]

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]

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]

Citations

1. United States 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. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation treatment of comorbid posttraumatic stress disorder and major depression. [2006]

3. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Is transcranial magnetic stimulation effective in treatment-resistant combat related posttraumatic stress disorder? [2014]

4. United States pubmed.ncbi.nlm.nih.gov

Test-retest assessment of cortical activation induced by repetitive transcranial magnetic stimulation with brain atlas-guided optical topography. [2019]

5. Ireland 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. [2007]

6. Netherlands 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. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Prefrontal transcranial magnetic stimulation for depression in US military veterans - A naturalistic cohort study in the veterans health administration. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Network Mechanisms of Clinical Response to Transcranial Magnetic Stimulation in Posttraumatic Stress Disorder and Major Depressive Disorder. [2020]

9. England pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation for post-traumatic stress disorder. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Using simultaneous repetitive Transcranial Magnetic Stimulation/functional Near Infrared Spectroscopy (rTMS/fNIRS) to measure brain activation and connectivity. [2023]

11. Switzerland pubmed.ncbi.nlm.nih.gov

A Systematic Review of Integrated Functional Near-Infrared Spectroscopy (fNIRS) and Transcranial Magnetic Stimulation (TMS) Studies. [2020]