Non-Invasive Brain Stimulation Techniques Development

Overseen By Neil G Baker

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: National Institute of Mental Health (NIMH)

Must not be taking: Tricyclics, Antipsychotics, Stimulants, others

Disqualifiers: Pregnancy, Axis I disorders, Seizures, others

Compensation: Varies

Number of Visits: 5

180 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore the use of non-invasive brain stimulation (NIBS) to improve the diagnosis and treatment of psychiatric and neurological conditions. Researchers are testing different methods, such as the location and duration of brain stimulation, while observing brain reactions during the process. Participants will complete various tasks and tests, including brain scans and muscle activity measurements. The trial seeks healthy individuals who are native English speakers without a history of neurological issues or certain medical conditions. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new diagnostic and treatment methods.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any medications that affect brain function, such as psychotropic drugs, and any medications that lower the seizure threshold.

What prior data suggests that these non-invasive brain stimulation techniques are safe?

Studies have shown that Transcranial Magnetic Stimulation (TMS) is generally safe. Most side effects are minor and manageable, such as mild headaches or scalp discomfort. Serious side effects are rare and can usually be avoided by adhering to safety guidelines. Unlike some other treatments, TMS does not cause seizures or memory loss and does not require anesthesia, making it less risky overall. For those considering participation in a clinical trial involving TMS, research indicates that the treatment has a strong safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about non-invasive brain stimulation techniques like Transcranial Magnetic Stimulation (TMS) because they offer a novel way to modulate brain activity without the need for surgery or medication. Unlike traditional treatments for conditions like depression, which often involve pharmaceuticals targeting neurotransmitters, TMS uses magnetic fields to stimulate nerve cells in the brain directly. This method holds promise for fewer side effects and a more targeted approach. Additionally, the use of sham TMS as a placebo helps refine our understanding of TMS's effectiveness, potentially leading to more personalized and effective mental health treatments.

What evidence suggests that these brain stimulation techniques could be effective?

This trial will compare Transcranial Magnetic Stimulation (TMS) with Sham TMS. Studies have shown that TMS can improve symptoms of major depression. Research indicates that TMS is particularly effective for individuals whose depression hasn't improved with other treatments, increasing their chances of recovery. A large review of many studies found that the right amount of TMS leads to better mental health outcomes. TMS uses magnetic fields to stimulate brain cells, which can enhance mood and mental function. Overall, evidence supports TMS as a promising non-invasive option for treating psychiatric and neurological conditions. ^{3 6 7 8 9}

Who Is on the Research Team?

Carlos A Zarate, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Are You a Good Fit for This Trial?

Healthy English speakers aged 18-65 can join this trial. It's not for pregnant or breastfeeding women, those with serious medical conditions, hearing loss, metal implants, claustrophobia in MRI machines, drug/alcohol abuse history within a year, or anyone at increased risk of seizures.

Inclusion Criteria

I am a native English speaker.

Subjects must be able to give written informed consent prior to participation in this study

All subjects must have undergone a screening assessment under protocol 01-M-0254, The Evaluation of Patients with Mood and Anxiety Disorders and Healthy Volunteers or under protocol 17-M-0181 (Recruitment and Characterization of Research Volunteers for NIMH Intramural Studies)

Exclusion Criteria

I am not pregnant or breastfeeding.

I haven't had seizures, epilepsy, stroke, brain surgery, or serious head trauma recently.

A current NIMH employee or staff or their immediate family member

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 hours

1 visit (in-person)

Baseline

Participants undergo baseline procedures including MRI and training in behavioral tasks

Varies

Experimental NIBS Sessions

Participants engage in up to 4 sessions per substudy involving NIBS with EEG, EMG, and/or fMRI

1-3 hours per session

Up to 4 visits per substudy

Follow-up

Participants are monitored for safety and effectiveness after NIBS sessions

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Sham TMS
• TMS

Trial Overview The study tests non-invasive brain stimulation (NIBS) techniques like Transcranial Magnetic Stimulation (TMS) and Sham TMS to improve their effectiveness. Participants will undergo behavioral tests, muscle activity measurement, brain imaging (MRI), and brain wave recording (EEG).

How Is the Trial Designed?

Group I: arm 1 Experimental Treatment 1 Intervention

these are within subject repeated measures studies across a number of conditions

Group II: arm 2 Placebo Group 1 Intervention

these are within subject repeated measures studies across a number of conditions (which can include sham TMS as a placebo)

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

Transcranial magnetic stimulation (TMS) was successfully used in a 2-year-old boy with EBV encephalitis, leading to improvements in mutism, ataxia, and other neurological deficits after treatment.

The case suggests that TMS can normalize decreased brain cortex activity, indicating its potential as a therapeutic tool for various neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation. A case report and review of the literature. Anninos, P., Kotini, A., Tamiolakis, D., et al.[2006]

Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation technique that offers advantages over other methods like vagus nerve stimulation and deep brain stimulation, which require surgery or anesthesia.

TMS has shown promise in various areas, including as a therapeutic tool for neuropsychiatric conditions, a research instrument in neuroscience, and a potential method to enhance cognitive performance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms and the current state of transcranial magnetic stimulation. George, MS., Nahas, Z., Kozol, FA., et al.[2019]

Transcranial magnetic stimulation (TMS) is safe to use with implanted deep brain stimulation (DBS) devices at low to moderate intensities, as no movement or temperature increase was observed during stimulation at 0.2 Hz with 100% intensity for 1 hour.

However, caution is advised when using high-intensity TMS (over 50%) near looped DBS leads, as it can exceed the safety limit for charge density, potentially leading to electrical tissue injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of transcranial magnetic stimulation with deep brain stimulation instruments. Shimojima, Y., Morita, H., Nishikawa, N., et al.[2010]

Sham transcranial magnetic stimulation (TMS) is commonly used in research to differentiate real effects from side effects, but it has limitations in accurately controlling for placebo and sensory effects.

The authors argue that sham TMS cannot fully serve as a control condition because it does not adequately demonstrate the specificity of TMS effects, suggesting that it should be used alongside other control strategies in TMS studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rethinking the role of sham TMS. Duecker, F., Sack, AT.[2020]

In a study involving 33 patients undergoing rTMS treatment, the sham condition used was effective as most participants could not distinguish between real and sham stimulation, indicating its suitability for clinical trials.

Both groups, those receiving real stimulation and those receiving sham, showed a high willingness to recommend rTMS to others, suggesting that the treatment is perceived positively regardless of the actual stimulation received.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sham or real--post hoc estimation of stimulation condition in a randomized transcranial magnetic stimulation trial. Herwig, U., Cardenas-Morales, L., Connemann, BJ., et al.[2015]

The new 'sandwich' TMS setup significantly reduces the magnetic field in the sham condition to about one eighth of that in the active stimulation condition, effectively minimizing unwanted stimulation of both the targeted brain area and neighboring regions.

This innovative design allows researchers to conduct TMS studies with a reliable sham condition, ensuring that subjects cannot distinguish between active and sham stimulation based on external cues, thus improving the overall quality of TMS research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation--a sandwich coil design for a better sham. Sommer, J., Jansen, A., Dräger, B., et al.[2021]

The eSham system is a new portable sham TMS technology designed to mimic the scalp sensations of real TMS, addressing a major limitation in TMS research related to traditional sham techniques.

Preliminary results from a study with 9 healthy adults showed that the eSham system produced similar sensory experiences and tolerability ratings compared to real TMS, suggesting it could be a valid option for future clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development and evaluation of a portable sham transcranial magnetic stimulation system. Borckardt, JJ., Walker, J., Branham, RK., et al.[2021]

Different sham transcranial magnetic stimulation (TMS) techniques can produce varying levels of cortical stimulation, with some sham conditions inducing significant brain activity, which could affect trial outcomes.

The study found that a two-wing 45-degree tilt sham condition resulted in only 24% lower voltage than active TMS, indicating that not all sham methods are equally effective in mimicking a true placebo, highlighting the importance of selecting appropriate sham techniques in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sham TMS: intracerebral measurement of the induced electrical field and the induction of motor-evoked potentials. Lisanby, SH., Gutman, D., Luber, B., et al.[2022]

In a meta-analysis of 93 randomized controlled trials involving repetitive transcranial magnetic stimulation (TMS), the overall incidence of adverse events (AEs) was found to be higher in the active TMS group (29.3%) compared to the placebo group (13.6%), indicating a 2.60 times greater risk of experiencing AEs with active treatment.

Despite the higher incidence of AEs, TMS is considered a safe and well-tolerated intervention, with common side effects including headache and dizziness, highlighting the importance of recognizing nocebo effects in both clinical trials and practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Tolerability, and Nocebo Phenomena During Transcranial Magnetic Stimulation: A Systematic Review and Meta-Analysis of Placebo-Controlled Clinical Trials. Zis, P., Shafique, F., Hadjivassiliou, M., et al.[2022]

The study introduces a novel electronic targeting method for transcranial magnetic stimulation (TMS) using a set of overlapping coils, allowing for faster and more precise stimulation of specific brain areas without the need for physical coil movement.

With just two coils, the device can adjust the stimulation location along a 30-mm line in the cortex, demonstrating a significant advancement in TMS technology that could enhance research and therapeutic applications in brain stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-locus transcranial magnetic stimulation-theory and implementation. Koponen, LM., Nieminen, JO., Ilmoniemi, RJ.[2019]

The newly developed multi-locus transcranial magnetic stimulation (mTMS) system allows for precise electronic control of the stimulation location and orientation within a targeted cortical area, enhancing the ability to stimulate specific brain regions.

In a proof-of-concept experiment with a healthy volunteer, the mTMS system successfully demonstrated that varying the position of the induced electric field resulted in consistent changes in motor evoked potentials, confirming its efficacy in targeted brain stimulation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Multi-locus transcranial magnetic stimulation system for electronically targeted brain stimulation. Nieminen, JO., Sinisalo, H., Souza, VH., et al.[2022]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK568715/

Repetitive Transcranial Magnetic Stimulation - StatPearls - NCBI Repetitive transcranial magnetic stimulation utilizes non-invasive brain stimulation and has shown promising results for diagnostic and ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1935861X24001128

Treatment expectations and clinical outcomes following ... Positive pre-treatment expectancy boosts remission odds in Treatment-Resistant Depression (TRD) after acute rTMS.

3. mayoclinic.org mayoclinic.org/tests-procedures/transcranial-magnetic-stimulation/about/pac-20384625

Transcranial magnetic stimulation Transcranial magnetic stimulation (TMS) is a procedure that uses magnetic fields to stimulate nerve cells in the brain to improve symptoms of major depression.

4. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2818884

Transcranial Magnetic Stimulation and ... This systematic review and dose-response meta-analysis of 110 studies in 4820 participants found that significant dose-response associations were observed for ...

5. psychiatrist.com psychiatrist.com/pcc/effectiveness-repetitive-transcranial-magnetic-stimulation-depression-schizophrenia-obsessive-compulsive-disorder-umbrella-meta-analysis/

Effectiveness of Repetitive Transcranial Magnetic ... In treatment-resistant depression, repetitive transcranial magnetic stimulation had higher odds of response and remission rates compared to ...

6. nimh.nih.gov nimh.nih.gov/news/media/2020/sarah-h-lisanby-transcranial-magnetic-stimulation-safety-and-risk

Sarah H. Lisanby: Transcranial Magnetic Stimulation ... The safety profile of TMS is excellent. The common side effects tend to be minor and are easily managed. The serious side effects are rare and can be prevented ...

7. fda.gov fda.gov/medical-devices/guidance-documents-medical-devices-and-radiation-emitting-products/repetitive-transcranial-magnetic-stimulation-rtms-systems-class-ii-special-controls-guidance

Repetitive Transcranial Magnetic Stimulation (rTMS) Systems This guidance document was developed as a special controls guidance to support the classification of Repetitive Transcranial Magnetic Stimulation (r TMS) ...

8. sciencedirect.com sciencedirect.com/science/article/pii/S1388245720305149

Safety and recommendations for TMS use in healthy ... The risks of stimulation can be subject-dependent. A stimulation dose that is safe for one subject may not be safe for another, e.g., because of a different ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9879417/

Safety Review for Clinical Application of Repetitive ... Repetitive transcranial magnetic stimulation (rTMS) conforming to the safety guideline is generally safe. • Any precautions and risks for rTMS should be ...