eTMS for Stress-Related Disorders

(ETMS4Stress Trial)

Overseen By Neil B Austin

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Marcia Bockbrader, MD PhD

Disqualifiers: Uncontrolled conditions, Active addiction, Pregnancy, others

Stay on Your Current Meds You can continue your current medications while participating

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 30

Duration: 6 weeks

30 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn about the safety, feasibility, and preliminary efficacy of EEG-enhanced transcranial magnetic stimulation (eTMS) as an adjunct to standard-of-care therapies for chronic trauma and stressor related disorders (TSRD) among US military veterans. The main questions the study aims to answer are: * Is it safe to provide 30 sessions of eTMS for veterans with chronic TSRD? * Is it feasible to provide 30 sessions of eTMS as an adjunct to standard-of-care therapies for veterans with chronic TSRD? * Does health-related quality of life improve among veterans after 30 sessions of eTMS as an adjunct to standard-of-care therapies for chronic TSRD? Participants will undergo 30 sessions of eTMS as an adjunct to standard-of-care therapies for veterans with chronic TSRD, weekly reassessment during treatment, and intermittent follow-up for 36 weeks post-enrollment.

Do I need to stop my current medications for the eTMS trial?

The trial does not specify if you need to stop your current medications. It mentions that eTMS is an adjunct to standard-of-care therapies, which suggests you may continue your existing treatments.

What data supports the effectiveness of the treatment eTMS for stress-related disorders?

Research shows that transcranial magnetic stimulation (TMS), especially when combined with EEG, can help improve symptoms in people with psychiatric disorders by modulating brain activity. This suggests that eTMS might be effective for stress-related disorders by targeting and adjusting brain circuits involved in these conditions. ^{1 2 3 4 5}

Is eTMS safe for humans?

eTMS, also known as transcranial magnetic stimulation (TMS), is generally considered safe for humans, with common minor side effects like headaches. However, there is a low risk of seizures, especially at high intensities, and guidelines exist to minimize these risks. ^{6 7 8 9 10}

How is eTMS different from other treatments for stress-related disorders?

eTMS (electromagnetic transcranial magnetic stimulation) is unique because it uses magnetic fields to noninvasively stimulate specific areas of the brain, potentially modulating neural circuits and improving symptoms in stress-related disorders. Unlike traditional treatments, eTMS can directly target and alter brain activity, offering a novel approach to managing these conditions. ^{3 4 11 12 13}

Eligibility Criteria

This trial is for US military veterans with chronic trauma and stressor-related disorders who have experienced deployment-related stressful events. They must be enrolled in addiction or opioid reduction services if applicable, agree to limit alcohol intake, and not exceed a certain daily dose of opioids. Those with uncontrolled medical conditions, active untreated addictions (except cannabis), or contraindications to TMS like metal implants are excluded.

Inclusion Criteria

Positive identification as a Veteran per discharge paperwork (DD-214, DD-215, NGB-22, NGB-22A) and photo ID, or Veterans Health Administration Veteran Health Identification Card (VHIC)

Agreement to limit daily alcoholic beverage consumption to no more than 2 servings

Informed consent for study participation, off label-eTMS, and data use

Exclusion Criteria

Uncontrolled medical, psychological or neurological conditions including, but not limited to: uncontrolled psychosis or mania, uncontrolled seizure disorder or EEG abnormalities that indicate risk of seizure, i.e., epileptiform discharges during the EEG recording, uncontrolled cardiac, pulmonary, or endocrine disorder (e.g., diabetes), acute pain or illness, active, untreated addiction to prescription drugs, alcohol or illicit substances (not including cannabis or derivatives, which are available in many states under medical prescription or for recreational use), clinically significant medical condition or abnormality that in the Investigator's judgment might pose a potential safety risk to the subject or limit the interpretation of the trial results, pregnant, or female unwilling to use effective birth control during the course of the trial (unless cleared for participation by obstetrician/gynecologist), absolute contraindications to TMS: presence of aneurysm clips or coils, cochlear or ocular implant, cortical epidural stimulator, deep brain stimulator, pacemaker or defibrillator, retained intracranial metal foreign body (bullets, shrapnel - excluding titanium and oral implants), steel stents or shunts, active vagal nerve stimulator, ventriculoperitoneal (VP) shunt, prior TMS treatment, unwilling or unable to adhere to the study treatment, data collection schedule, or study procedures

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 30 sessions of eTMS as an adjunct to standard-of-care therapies for veterans with chronic TSRD

6 weeks

30 sessions (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

36 weeks

Intermittent visits

Treatment Details

Interventions

• eTMS

Trial Overview The study tests the safety and effectiveness of EEG-enhanced transcranial magnetic stimulation (eTMS) as an additional treatment alongside standard care for veterans' chronic trauma disorders. It involves 30 sessions of eTMS over several weeks, with regular reassessments and follow-ups extending up to 36 weeks post-enrollment.

Participant Groups

Group I: Adjunctive eTMS treatment (no delay) Experimental Treatment 1 Intervention

6 weeks (30 sessions) of daily eTMS as an adjunct to standard of care TSRD treatment

Who Is Running the Clinical Trial?

Marcia Bockbrader, MD PhD

Lead Sponsor

Trials

1

Recruited

30+

Ohio Department of Mental Health and Addiction Services

Collaborator

Trials

1

Recruited

30+

Findings from Research

The integration of transcranial magnetic stimulation (TMS) with electroencephalographic (EEG) imaging allows researchers to gain real-time insights into how the brain reacts and connects, enhancing our understanding of brain function and behavior.

This TMS-EEG technique can reveal individual differences in brain responses and how these responses change during tasks, which could significantly advance both clinical applications and basic neuroscience research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combining TMS and EEG offers new prospects in cognitive neuroscience. Miniussi, C., Thut, G.[2009]

In a pilot study involving three patients with Panic Disorder who had not responded to other treatments, transcranial magnetic stimulation (TMS) showed only modest and partial symptom improvement after 10 sessions, which was not clinically significant.

An alternate TMS approach using both high and low frequency stimulation was well tolerated but did not lead to additional benefits, suggesting that while TMS is safe, its efficacy in treating Panic Disorder needs further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Panic disorder and transcranial magnetic stimulation]. García-Toro, M., Salva Coll, J., Crespí Font, M., et al.[2008]

Transcranial magnetic stimulation (TMS) is a noninvasive technique that can both assess and modulate brain activity, showing promise in treating psychiatric disorders by targeting specific cortical areas.

Combining TMS with EEG (TMS-EEG) allows researchers to objectively study brain functions and has been effective in improving symptoms in conditions like schizophrenia and mood disorders, paving the way for personalized treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Examining and Modulating Neural Circuits in Psychiatric Disorders With Transcranial Magnetic Stimulation and Electroencephalography: Present Practices and Future Developments. Ferrarelli, F., Phillips, ML.[2022]

The review highlights the use of concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) to explore neural mechanisms in various psychiatric disorders, which could enhance diagnostic accuracy and lead to new treatment options.

TMS-EEG has shown promise in identifying alterations in brain activity patterns, such as cortical excitability and connectivity, which may serve as biomarkers for predicting treatment responses in conditions like major depressive disorder and schizophrenia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

TMS-EEG: An emerging tool to study the neurophysiologic biomarkers of psychiatric disorders. Cao, KX., Ma, ML., Wang, CZ., et al.[2022]

TMS-EEG is a non-invasive technique that combines transcranial magnetic stimulation with electroencephalography, allowing researchers to study brain circuits and assess properties like excitability and connectivity in various clinical populations.

This review highlights the potential of TMS-EEG to identify predictors of treatment response and understand the underlying mechanisms of brain disorders, suggesting it could be a valuable tool for improving clinical outcomes in psychiatric and neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical utility and prospective of TMS-EEG. Tremblay, S., Rogasch, NC., Premoli, I., et al.[2022]

Transcranial magnetic stimulation (TMS) is generally safe and does not cause persistent changes in cognitive function or EEG, although transient effects may occur during treatment.

While TMS does not typically induce seizures, there is a potential risk for individuals with heightened susceptibility, indicating that further research is needed to fully understand any unwanted effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of transcranial magnetic stimulation reconsidered: evidence regarding cognitive and other cerebral effects. Bridgers, SL.[2007]

In a study involving 9 normal volunteers, rapid-rate transcranial magnetic stimulation (rTMS) was found to be generally safe, but it caused temporary hearing threshold shifts in 3 subjects and a seizure in one subject at the highest intensity, indicating a potential risk for seizures.

The study also demonstrated that rTMS can increase cortical excitability in contralateral muscles, with the extent of this effect varying based on the intensity and frequency of the stimulation, suggesting a need for careful monitoring and guidelines to mitigate side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of rapid-rate transcranial magnetic stimulation in normal volunteers. Pascual-Leone, A., Houser, CM., Reese, K., et al.[2019]

Repetitive Transcranial Magnetic Stimulation (rTMS) has a good overall safety profile for treating depression, with common side effects like headaches being minor and manageable.

While there is a low incidence of serious side effects such as seizures and hypomania, these are linked to specific risk factors, suggesting that proper screening can enhance patient safety during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. Loo, CK., McFarquhar, TF., Mitchell, PB.[2021]

Repetitive transcranial magnetic stimulation (rTMS) is a powerful tool that can effectively treat clinical depression and potentially other brain disorders, but it carries risks, including the potential to induce seizures, as evidenced by 7 known cases by 1996.

A workshop established safety guidelines for rTMS, emphasizing the importance of monitoring, ethical considerations, and the expertise required for its administration to minimize risks and enhance therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. Wassermann, EM.[2022]

A patient with treatment-resistant depression (TRD) showed unexpected improvement after experiencing a seizure during repetitive transcranial magnetic stimulation (rTMS), suggesting a potential link between seizure activity and therapeutic effects in TRD.

While rTMS is generally safe, known adverse events include headaches and seizures; this case highlights an unusual outcome where a seizure may have contributed to the patient's improvement, warranting further investigation into the mechanisms of rTMS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. Kim, JW., Bae, KY., Kim, SW., et al.[2020]

Continuous EEG monitoring during repetitive transcranial magnetic stimulation (rTMS) in patients with major depression, schizophrenia, and obsessive-compulsive disorder can enhance safety by tracking ongoing brain activity, especially when stimulation parameters exceed standard safety guidelines.

The combination of EEG and rTMS may provide valuable insights into brain physiology and the specific effects of magnetic stimulation, although this area remains largely underexplored in current research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electroencephalogram and repetitive transcranial magnetic stimulation. Boutros, NN., Berman, RM., Hoffman, R., et al.[2006]

In a study involving 17 healthy young individuals, the researchers found that the EEG responses to Transcranial Magnetic Stimulation (TMS) closely resembled those from sham stimulation, indicating that peripheral sensory and auditory stimuli significantly influence TMS-evoked EEG potentials (TEPs).

The results highlight the importance of controlling for multisensory effects in TMS-EEG studies, as the similarities in TEPs suggest that distinguishing between true cortical activation and responses from peripheral stimulation is crucial for accurate interpretation of TMS effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies. Conde, V., Tomasevic, L., Akopian, I., et al.[2022]

Transcranial magnetic stimulation (TMS) at intensities above resting motor threshold (RMT) produces significantly stronger cortical responses compared to sham stimulation, indicating effective direct activation of neurons.

In this study with 12 healthy subjects, TMS at 110% RMT resulted in the highest amplitudes of TMS evoked potentials and increased beta power, demonstrating that TMS can selectively enhance specific brain oscillations, distinguishing it from non-specific sensory responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of cortical EEG responses to realistic sham versus real TMS of human motor cortex. Gordon, PC., Desideri, D., Belardinelli, P., et al.[2022]

References

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

Combining TMS and EEG offers new prospects in cognitive neuroscience. [2009]

2. Spain pubmed.ncbi.nlm.nih.gov

[Panic disorder and transcranial magnetic stimulation]. [2008]

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

Examining and Modulating Neural Circuits in Psychiatric Disorders With Transcranial Magnetic Stimulation and Electroencephalography: Present Practices and Future Developments. [2022]

4. England pubmed.ncbi.nlm.nih.gov

TMS-EEG: An emerging tool to study the neurophysiologic biomarkers of psychiatric disorders. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Clinical utility and prospective of TMS-EEG. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

The safety of transcranial magnetic stimulation reconsidered: evidence regarding cognitive and other cerebral effects. [2007]

7. Ireland pubmed.ncbi.nlm.nih.gov

Safety of rapid-rate transcranial magnetic stimulation in normal volunteers. [2019]

8. England pubmed.ncbi.nlm.nih.gov

A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. [2021]

9. Ireland pubmed.ncbi.nlm.nih.gov

Risk and safety of repetitive transcranial magnetic stimulation: report and suggested guidelines from the International Workshop on the Safety of Repetitive Transcranial Magnetic Stimulation, June 5-7, 1996. [2022]

10. Korea (South) pubmed.ncbi.nlm.nih.gov

Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. [2020]

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

Electroencephalogram and repetitive transcranial magnetic stimulation. [2006]

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

The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies. [2022]

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

Comparison of cortical EEG responses to realistic sham versus real TMS of human motor cortex. [2022]