eTMS for Stress-Related Disorders
(ETMS4Stress Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Marcia Bockbrader, MD PhD
Disqualifiers: Uncontrolled conditions, Active addiction, Pregnancy, others
Stay on Your Current Meds
No Placebo Group
Prior Safety Data
Approved in 2 Jurisdictions
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.
12345Is 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.
678910How 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.
34111213Eligibility 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
+6 more
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
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Adjunctive eTMS treatment (no delay)Experimental Treatment1 Intervention
6 weeks (30 sessions) of daily eTMS as an adjunct to standard of care TSRD treatment
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
BEP Medical Group LLCColumbus, OH
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Who Is Running the Clinical Trial?
Marcia Bockbrader, MD PhDLead Sponsor
Ohio Department of Mental Health and Addiction ServicesCollaborator
References
Combining TMS and EEG offers new prospects in cognitive neuroscience. [2009]The combination of brain stimulation by transcranial magnetic stimulation (TMS) with simultaneous electroencephalographic (EEG) imaging has become feasible due to recent technical developments. The TMS-EEG integration provides real-time information on cortical reactivity and connectivity through the analysis of TMS-evoked potentials (TEPs), and how functional activity links to behavior through the study of TMS-induced modulations thereof. It reveals how these effects vary as a function of neuronal state, differing between individuals and patient groups but also changing rapidly over time during task performance. This review discusses the wide range of possible TMS-EEG applications and what new information may be gained using this technique on the dynamics of brain functions, hierarchical organization, and cortical connectivity, as well as on TMS action per se. An advance in the understanding of these issues is timely and promises to have a substantial impact on many areas of clinical and basic neuroscience.
[Panic disorder and transcranial magnetic stimulation]. [2008]Transcranial magnetic stimulation (TMS) has been tried in some Anxiety Disorders (Obsessive-compulsive disorder and Posttraumatic Stress Disorder) with different results. We present a pilot study including three Panic Disorder patients. The subjects who were enrolled had a history of the disease for at least 1 year and they had unsuccessfully followed psychotherapy and pharmacological treatment. The patients received 10 sessions during two weeks; each session lasted 30 trains of 60 seconds at a frequency of 1 Hz, on the right dorsolateral prefrontal cortex, at 110% of the motor threshold. All three patients experienced a modest and partial symptom improvement that did not seemed to be clinically relevant. Two patients accepted to participate in a TMS second phase, where the previous stimulation parameters were alternated with an application of 30 trains of 20 Hz during 2 seconds on the left prefrontal cortex. This alternate application of high and low frequency TMS in each session was also well tolerated, but failed to produce additional improvement. In addition to presenting these three cases, we emphasize some features concerning the neurobiological basis of the anxiety disorders and we connect them to the previously described TMS neurophysiological actions in order to justify further investigation.
Examining and Modulating Neural Circuits in Psychiatric Disorders With Transcranial Magnetic Stimulation and Electroencephalography: Present Practices and Future Developments. [2022]Transcranial magnetic stimulation (TMS) is a noninvasive brain stimulation technique uniquely equipped to both examine and modulate neural systems and related cognitive and behavioral functions in humans. As an examination tool, TMS can be used in combination with EEG (TMS-EEG) to elucidate directly, objectively, and noninvasively the intrinsic properties of a specific cortical region, including excitation, inhibition, reactivity, and oscillatory activity, irrespective of the individual's conscious effort. Additionally, when applied in repetitive patterns, TMS has been shown to modulate brain networks in healthy individuals, as well as ameliorate symptoms in individuals with psychiatric disorders. The key role of TMS in assessing and modulating neural dysfunctions and associated clinical and cognitive deficits in psychiatric populations is therefore becoming increasingly evident. In this article, the authors review TMS-EEG studies in schizophrenia and mood disorders, as most TMS-EEG studies to date have focused on individuals with these disorders. The authors present the evidence on the efficacy of repetitive TMS (rTMS) and theta burst stimulation (TBS), when targeting specific cortical areas, in modulating neural circuits and ameliorating symptoms and abnormal behaviors in individuals with psychiatric disorders, especially when informed by resting-state and task-related neuroimaging measures. Examples of how the combination of TMS-EEG assessments and rTMS and TBS paradigms can be utilized to both characterize and modulate neural circuit alterations in individuals with psychiatric disorders are also provided. This approach, along with the evaluation of the behavioral effects of TMS-related neuromodulation, has the potential to lead to the development of more effective and personalized interventions for individuals with psychiatric disorders.
TMS-EEG: An emerging tool to study the neurophysiologic biomarkers of psychiatric disorders. [2022]The etiology of psychiatric disorders remains largely unknown. The exploration of the neurobiological mechanisms of mental illness helps improve diagnostic efficacy and develop new therapies. This review focuses on the application of concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) in various mental diseases, including major depressive disorder, bipolar disorder, schizophrenia, autism spectrum disorder, attention-deficit/hyperactivity disorder, substance use disorder, and insomnia. First, we summarize the commonly used protocols and output measures of TMS-EEG; then, we review the literature exploring the alterations in neural patterns, particularly cortical excitability, plasticity, and connectivity alterations, and studies that predict treatment responses and clinical states in mental disorders using TMS-EEG. Finally, we discuss the potential mechanisms underlying TMS-EEG in establishing biomarkers for psychiatric disorders and future research directions. This article is part of the special Issue on 'Stress, Addiction and Plasticity'.
Clinical utility and prospective of TMS-EEG. [2022]Concurrent transcranial magnetic stimulation and electroencephalography (TMS-EEG) has emerged as a powerful tool to non-invasively probe brain circuits in humans, allowing for the assessment of several cortical properties such as excitability and connectivity. Over the past decade, this technique has been applied to various clinical populations, enabling the characterization and development of potential TMS-EEG predictors and markers of treatments and of the pathophysiology of brain disorders. The objective of this article is to present a comprehensive review of studies that have used TMS-EEG in clinical populations and to discuss potential clinical applications. To provide a technical and theoretical framework, we first give an overview of TMS-EEG methodology and discuss the current state of knowledge regarding the use of TMS-EEG to assess excitability, inhibition, plasticity and connectivity following neuromodulatory techniques in the healthy brain. We then review the insights afforded by TMS-EEG into the pathophysiology and predictors of treatment response in psychiatric and neurological conditions, before presenting recommendations for how to address some of the salient challenges faced in clinical TMS-EEG research. Finally, we conclude by presenting future directions in line with the tremendous potential of TMS-EEG as a clinical tool.
The safety of transcranial magnetic stimulation reconsidered: evidence regarding cognitive and other cerebral effects. [2007]The potential of transcranial magnetic stimulation (TMS) to cause undesired or unexpected effects on cognition and other cerebral functions has received only limited study, although extensive clinical use has suggested that obvious problems are unlikely. Evidence so far accumulated suggests that exposure to TMS in the expected clinical situations will have no persistent effects on the electroencephalogram (EEG) or on cognitive function, although transient effects may occur. The absence of increases in either prolactin or adrenocorticotropic hormone (ACTH) in subjects undergoing TMS indicates that seizure-like events do not routinely occur, although recent evidence suggests that TMS may cause seizures or enhance the occurrence of epileptiform abnormalities in circumstances of heightened susceptibility. Despite these observations, treated seizure patients are unlikely to experience seizures with TMS. The technique is generally safe, but not entirely free from unwanted effects, and further study to define those effects is warranted.
Safety of rapid-rate transcranial magnetic stimulation in normal volunteers. [2019]In 9 normal volunteers, we studied the safety of rapid-rate transcranial magnetic stimulation (rTMS) applied to different scalp positions at various frequencies and intensities. Pure tone threshold audiometry showed temporary threshold shifts in 3 subjects. In the subject stimulated at the highest intensity, rTMS induced a focal, secondarily generalized seizure despite the absence of definite risk factors for seizures. Rapid-rate TMS did not result in any important changes in the neurological examination findings, cognitive performance, electroencephalogram, electrocardiogram, and hormone levels (prolactin, adrenocorticotropic hormone, thyroid-stimulating hormone, luteinizing hormone, and follicle-stimulating hormone). In 10 additional subjects, the electromyographic activity in several contralateral muscles showed that trains of rTMS applied to the motor cortex induced a spread of cortical excitability. The spread of excitability depended on the intensity and frequency of the stimuli and probably constituted an early epileptogenic effect of rTMS. Guidelines for preventing the undesirable side effects of rTMS are offered.
A review of the safety of repetitive transcranial magnetic stimulation as a clinical treatment for depression. [2021]There is growing interest worldwide in rTMS as a clinical treatment for depression. Apart from efficacy, its safety as a clinical treatment must be considered before its widespread use can be advocated. All published, sham-controlled rTMS depression trials were reviewed for reported side-effects and outcomes of formal neuropsychological testing. In addition, all reports of seizures occurring with rTMS were reviewed. Other safety concerns (effects on hearing; headache, pain, induced currents in electrical circuits, histotoxicity, electromagnetic field exposure, psychiatric complications, safety in pregnancy) are discussed. Common side-effects were of a minor nature, e.g. headache. There was a low incidence of accidental seizures and induced hypomania, both of which were associated with identified risk factors for which subjects should be screened. Long-term effects of repeated rTMS sessions are as yet unknown. When given within recommended guidelines, the overall safety profile of rTMS is good, and supports its further development as a clinical treatment.
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]Single-pulse transcranial magnetic stimulation (TMS) is a safe and useful tool for investigating various aspects of human neurophysiology, particularly corticospinal function, in health and disease. Repetitive TMS (rTMS), however, is a more powerful and potentially dangerous modality, capable of regionally blocking or facilitating cortical processes. Although there is evidence that rTMS is useful for treating clinical depression, and possibly other brain disorders, it had caused 7 known seizures by 1996 and could have other undesirable effects. In June 1996 a workshop was organized to review the available data on the safety of rTMS and to develop guidelines for its safe use. This article summarizes the workshop's deliberations. In addition to issues of risk and safety, it also addresses the principles and applications of rTMS, nomenclature, and potential therapeutic effects of rTMS. The guidelines for the use of rTMS, which are summarized in an appendix, cover the ethical issues, recommended limits on stimulation parameters, monitoring of subjects (both physiologically and neuropsychologically), expertise and function of the rTMS team, medical and psychosocial management of induced seizures, and contra-indications to rTMS.
Treatment-Resistant Depression Entering Remission Following a Seizure during the Course of Repetitive Transcranial Magnetic Stimulation. [2020]Major depressive disorder is often resistant to antidepressant treatment. Repetitive transcranial magnetic stimulation (rTMS) has been used in treatment-resistant depression (TRD). Known adverse events of rTMS include transient headache, local pain, syncope, seizure induction, and hypomania induction. This report outlines a patient with TRD who unexpectedly improved following a seizure during the course of rTMS, which has never been reported.
Electroencephalogram and repetitive transcranial magnetic stimulation. [2006]Scalp recordings of the electroencephalogram (EEG) have been used in association with repetitive transcranial magnetic stimulation (rTMS) investigations as a safety measure in monitoring ongoing EEG activity and as a neurophysiologic tool in examining the specific effects induced by the magnetic stimulus on the EEG or evoked potentials (EPs). Medline review on the use of EEG or EPs with rTMS reveals that this area has been largely unexplored. Limited available studies attest to the potential for studies combining EEG/EPs and rTMS to be useful in further elucidating the normal brain physiology. Herein, we report on our experience with continuous EEG sampling combined with rTMS in patients with major depression (n = 14), schizophrenia (n = 7), and obsessive-compulsive disorder (n = 5). Our data support the practice of using continuous EEG monitoring when the stimulation parameters fall outside established safety guidelines.
The non-transcranial TMS-evoked potential is an inherent source of ambiguity in TMS-EEG studies. [2022]Transcranial Magnetic Stimulation (TMS) excites populations of neurons in the stimulated cortex, and the resulting activation may spread to connected brain regions. The distributed cortical response can be recorded with electroencephalography (EEG). Since TMS also stimulates peripheral sensory and motor axons and generates a loud "click" sound, the TMS-evoked EEG potentials (TEPs) reflect not only neural activity induced by transcranial neuronal excitation but also neural activity due to somatosensory and auditory processing. In 17 healthy young individuals, we systematically assessed the contribution of multisensory peripheral stimulation to TEPs using a TMS-compatible EEG system. Real TMS was delivered with a figure-of-eight coil over the left para-median posterior parietal cortex or superior frontal gyrus with the coil being oriented perpendicularly or in parallel to the target gyrus. We also recorded the EEG responses evoked by realistic sham stimulation over the posterior parietal and superior frontal cortex, mimicking the auditory and somatosensory sensations evoked by real TMS. We applied state-of-the-art procedures to attenuate somatosensory and auditory confounds during real TMS, including the placement of a foam layer underneath the coil and auditory noise masking. Despite these precautions, the temporal and spatial features of the cortical potentials evoked by real TMS at the prefrontal and parietal site closely resembled the cortical potentials evoked by realistic sham TMS, both for early and late TEP components. Our findings stress the need to include a peripheral multisensory control stimulation in the design of TMS-EEG studies to enable a dissociation between truly transcranial and non-transcranial components of TEPs.
Comparison of cortical EEG responses to realistic sham versus real TMS of human motor cortex. [2022]The analysis of cortical responses to transcranial magnetic stimulation (TMS) recorded by electroencephalography (EEG) has been successfully applied to study human cortical physiology. However, in addition to the (desired) activation of cortical neurons and fibers, TMS also causes (undesired) indirect brain responses through auditory and somatosensory stimulation, which may contribute significantly to the overall EEG signal and mask the effects of intervention on direct cortical responses.