Transcranial Magnetic Stimulation for Brain Network Targeting

(NetworkTMS Trial)

Overseen By Lipeng Ning, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Disqualifiers: Pacemaker, Claustrophobia, Neurosurgery, 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: 2

50 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It is best to discuss this with the trial coordinators or your doctor.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation (rTMS)?

Research shows that rTMS can be effective in treating major depressive disorder, with precise targeting of brain networks being important for its success. Initial positive responses to rTMS for depression can predict future treatment success, and there is interest in its potential for other conditions like stroke and Parkinson's disease. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS), including its repetitive form (rTMS), has been studied for safety since the 1990s. While generally considered safe, it can cause mild side effects like headaches and nausea, and in rare cases, seizures. Safety guidelines have been established to minimize risks, and these guidelines have been updated over the years to ensure safe use in both healthy individuals and those with neuropsychiatric conditions. ^{6 7 8 9 10}

How is the treatment Transcranial Magnetic Stimulation (rTMS) unique compared to other treatments for brain disorders?

Transcranial Magnetic Stimulation (rTMS) is unique because it is a non-invasive and painless method that uses magnetic fields to stimulate specific areas of the brain, potentially altering brain network activity. Unlike other treatments, rTMS can target specific brain networks and regions, such as the motor cortex or dorsolateral prefrontal cortex, to influence brain function and promote rehabilitation, making it a promising option for conditions like depression and motor function disorders. ^{5 11 12 13 14}

What is the purpose of this trial?

The goal of this study is to develop and validate an approach for accurate targeting and stimulation of brain networks using transcranial magnetic stimulation (TMS) using information from magnetic resonance imaging (MRI) data. This study requires two visits from each participant. In the first visit, the participant will be scanned by MRI scanners to collect data from the brain. Next, the data will be analyzed by the researcher to model the connections between different regions of the brain to determine the stimulation areas related to the so-called frontoparietal network. In the second visit, the participants will take four TMS sessions with different types of stimulations applied to the computed targets and complete a computer-based task named multi-source interference task. Electroencephalogram (EEG) data will be collected during the TMS stimulations and tasks. The main hypothesis is that applying TMS stimulations to the brain targets reduces the response time and response error in the tasks.

Eligibility Criteria

This clinical trial is for healthy volunteers interested in contributing to research on brain stimulation. Participants will undergo MRI scans and TMS sessions while completing tasks, with the aim of improving response times and accuracy.

Inclusion Criteria

I understand the study and can agree to participate.

No metal implants

Absent of lesions or tumors from MRI scans

Exclusion Criteria

Prosthetic heart valves

The presence of a cardiac pacemaker or pacemaker wires

I have had brain surgery or have metal clips in my head.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

MRI Data Collection

Participants undergo MRI scanning to collect brain data for analysis

1 visit

1 visit (in-person)

TMS Treatment

Participants receive TMS stimulations and perform computer-based tasks

1 visit

1 visit (in-person)

Follow-up

Participants are monitored for response time and response error in tasks

4 weeks

Treatment Details

Interventions

• Transcranial Magnetic Stimulation

Trial Overview The study tests a new method for targeting brain networks using Transcranial Magnetic Stimulation (TMS) guided by MRI data. It involves two visits: one for MRI scanning and another for four TMS sessions with EEG monitoring during task performance.

Participant Groups

Group I: Transcranial Magnetic Stimulation Experimental Treatment 1 Intervention

TMS with the intermittent theta burst stimulation protocol will be applied to the computed brain targets based on the MRI data of each participants.

Group II: Sham Transcranial Magnetic Stimulation Placebo Group 1 Intervention

Sham TMS coils will be applied to stimulate the brain targets. No magnetic field will be generated using the sham coil. It will play sounds similar to the true TMS stimulations with the pulsed weak electric current applied to the scalp to generate a similar feeling as in true stimulations.

Transcranial Magnetic Stimulation is already approved in United States, Canada, European Union for the following indications:

Approved in United States as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder
• Obsessive Compulsive Disorder

Approved in Canada as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Approved in European Union as Transcranial Magnetic Stimulation for:

• Major Depressive Disorder

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Findings from Research

Repetitive transcranial magnetic stimulation (rTMS) is a promising non-invasive brain stimulation technique that can enhance brain excitability and potentially improve conditions like stroke, Parkinson's disease, and depression, as discussed in a 2010 symposium with insights from both animal studies and small clinical trials.

While there is significant interest and some signs of therapeutic success with rTMS, the current models explaining its effects may need refinement to fully understand the underlying mechanisms and outcomes observed in various studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Brain stimulation and brain repair--rTMS: from animal experiment to clinical trials--what do we know? Platz, T., Rothwell, JC.[2013]

Repetitive magnetic stimulation (rTMS) is a non-invasive and painless technique that can effectively activate specific areas of the brain, making it useful for studying language, memory, and visual perception.

rTMS shows potential therapeutic benefits for conditions like movement disorders and depression, but there are safety considerations regarding its potential to induce seizures, which are addressed in the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. Brandt, SA., Ploner, CJ., Meyer, BU.[2019]

In a study involving 18 subjects with major depression, repetitive transcranial magnetic stimulation (rTMS) for up to 4 weeks was found to be generally safe, with no significant mean deficits in neuropsychologic function or auditory thresholds.

However, two patients experienced mild high-frequency hearing loss, indicating that while rTMS is safe for most, individual responses may vary and warrant further investigation into long-term safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. Loo, C., Sachdev, P., Elsayed, H., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) has not been thoroughly studied for side effects, with the main known risk being the acute production of seizures.

While tissue damage from rTMS is unlikely, there are concerns about potential cognitive effects and the possibility of long-term changes in brain function that have not yet been fully understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Side effects of repetitive transcranial magnetic stimulation. Wassermann, EM.[2005]

Repetitive transcranial magnetic stimulation (rTMS) has gained popularity for its ability to modulate brain activity, but safety considerations are crucial, especially with the recent updates to safety guidelines published in 2021.

The guidelines emphasize the importance of screening for risks, monitoring for adverse events, and specific safety measures when using rTMS, particularly in patients with conditions like stroke and traumatic brain injury.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. Kim, WS., Paik, NJ.[2023]

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]

Mild adverse effects (MAEs) from transcranial magnetic stimulation (TMS) occur in about 5% of sessions, with most symptoms like headache and nausea reported after the sessions, particularly during initial treatments.

The study found no significant links between participant characteristics (age and gender) or TMS parameters (frequency and intensity) and the occurrence of MAEs, suggesting that initial participant anxiety may play a role in these reports.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. Maizey, L., Allen, CP., Dervinis, M., et al.[2022]

References

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

Targeting location relates to treatment response in active but not sham rTMS stimulation. [2022]

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

Initial Response to Transcranial Magnetic Stimulation Treatment for Depression Predicts Subsequent Response. [2022]

3. Canada pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for the treatment of major depressive disorder: an evidence-based analysis. [2023]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Brain stimulation and brain repair--rTMS: from animal experiment to clinical trials--what do we know? [2013]

5. Germany pubmed.ncbi.nlm.nih.gov

[Repetitive transcranial magnetic stimulation. Possibilities, limits and safety aspects]. [2019]

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

Effects of a 2- to 4-week course of repetitive transcranial magnetic stimulation (rTMS) on neuropsychologic functioning, electroencephalogram, and auditory threshold in depressed patients. [2019]

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

Side effects of repetitive transcranial magnetic stimulation. [2005]

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

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023]

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. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative incidence rates of mild adverse effects to transcranial magnetic stimulation. [2022]

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

A neuronal network model for simulating the effects of repetitive transcranial magnetic stimulation on local field potential power spectra. [2021]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Altered Topological Organization in the Sensorimotor Network After Application of Different Frequency rTMS. [2020]

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

An integrated framework for targeting functional networks via transcranial magnetic stimulation. [2021]

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

Resting-state and task-based centrality of dorsolateral prefrontal cortex predict resilience to 1 Hz repetitive transcranial magnetic stimulation. [2021]