Brain Cooling with TMS for Healthy Subjects

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by Carlos A Zarate, M.D.

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Academic

Recruiting

Sponsor: National Institute of Mental Health (NIMH)

Must not be taking: Antidepressants, Anxiolytics, Anticonvulsants, others

Disqualifiers: Psychiatric conditions, Neurologic disorders, Implants, others

No Placebo Group

Approved in 2 Jurisdictions

Trial Summary

What is the purpose of this trial?

Sub-Study: Phase Triggered Paired Associative Stimulation (PAS) (actively recruiting) Background: -Previous research has shown that the brain s activity changes with changes in brain waves. We can study brain activity with a procedure called transcranial magnetic stimulation (TMS), a form of non-invasive brain stimulation. EEG allows for measuring ongoing brain waves. The goal of this study is to optimize TMS delivery by utilizing EEG-triggered TMS. Objectives: -To see if changes in brain waves change the brain and body s response to TMS. Eligibility: -Healthy, right-handed adults age 18-35. Design: * Participants will be screened under another protocol with medical history and physical exam. They may take a pregnancy test. They will have a magnetic resonance imaging (MRI) scan of the brain. For MRI, participants lie on a table that slides in and out of a metal tube that takes pictures. with: * Participants will have up to 4 outpatient visits lasting 2-3 hours each (4 outpatient visits). The following procedures may occur at a visit: * Magnetic resonance imaging (MRI): Participants lie on a table that slides into a machine that takes pictures of the brain. * Electroencephalography (EEG): Small electrodes on the scalp record brain waves. * Electromyography (EMG): Small sticky electrodes on the skin measure muscle activity. * Transcranial magnetic stimulation (TMS): A wire coil is held to the scalp. A brief electrical current passes through the coil and affects brain activity. Main Study: Influence on Plasticity of Brain Temperature (no longer recruiting) Background: - Brain activity changes with changes in body temperature. Brain activity can be studied with a procedure called transcranial magnetic stimulation (TMS). Researchers want to cool the brain through the scalp using a cooling cap. They want to see if cooling changes the brain and body s response to TMS. Objectives: - To look at the effects of cooling on the brain. Eligibility: - Right-handed adults age 18-50 who can abstain from caffeine and tobacco. Design: * Participants will be screened with medical history and physical exam. They will be asked about alcohol use, smoking, and substance abuse. They may take a pregnancy test. They may have a magnetic resonance imaging (MRI) scan of the brain. For MRI, participants lie on a table that slides in and out of a metal tube that takes pictures. * Participants will have 3 outpatient visits. The following procedures will occur at each visit. * Participants will wear a cooling cap for up to 45 minutes. Cool water will flow through the cap. It will feel like an ice pack in a towel. Their core temperature will be monitored. Their temperature will also be measured under their tongue and on scalp, stomach, forearm, and calf. * Participants will have TMS before and after wearing the cap. A brief electrical current will pass through a wire coil held on their scalp. Electrodes that detect muscle movement will be placed on their hand. They will also have repetitive TMS, which uses repeated magnetic pulses. Their wrist will also receive a shock.

Will I have to stop taking my current medications?

Yes, you will need to stop taking certain medications. The trial excludes participants who are taking medications such as antidepressants, anxiolytics (anti-anxiety drugs), anticonvulsants (anti-seizure drugs), antipsychotics, antiparkinson drugs, hypnotics (sleep aids), stimulants, and antihistamines.

What data supports the effectiveness of this treatment?

Research shows that Theta Burst Stimulation (TBS), a type of Transcranial Magnetic Stimulation (TMS), is effective in treating depression and is more energy- and time-efficient than standard repetitive TMS. Additionally, TBS has been studied for its effects on brain activity and recovery in stroke patients, suggesting its potential benefits in modulating brain function.

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Is brain cooling with TMS safe for healthy humans?

Transcranial Magnetic Stimulation (TMS) and its variations, like Repetitive TMS (rTMS) and Theta Burst Stimulation (TBS), have been studied for safety. Most adverse effects are mild, but there is a small risk of seizures, especially with high-frequency protocols like TBS. Safety guidelines exist to minimize these risks, and TMS is generally considered safe when applied with caution.

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How is the treatment of brain cooling with TMS unique compared to other treatments?

Brain cooling with TMS is unique because it combines transcranial magnetic stimulation (TMS), which uses magnetic pulses to stimulate the brain, with a cooling technique to manage heat generated during the process, potentially enhancing the treatment's effectiveness and duration.

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Eligibility Criteria

This trial is for healthy, right-handed adults aged 18-35 who can lie flat on their back for up to an hour. Participants must not have psychiatric conditions, be pregnant, or have a history of neurological disorders. They should not take certain medications and must abstain from caffeine and tobacco before visits.

Inclusion Criteria

I am between 18 and 50 years old.

I am between 18 and 35 years old.

Main Study:

Exclusion Criteria

I do not have clinically diagnosed hearing loss.

I am not on medication that increases my risk of seizures.

Participants with claustrophobia severe enough to prevent MRI scanning are excluded

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Main Study Treatment

Participants undergo cooling and TMS procedures to study the effects of cooling on brain plasticity

3 visits

3 visits (in-person)

Sub-study Treatment

Participants undergo EEG phase-triggered paired associative stimulation (PAS) to optimize TMS delivery

3-4 visits

3-4 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Participant Groups

The study tests how brain waves influence the body's response to Transcranial Magnetic Stimulation (TMS). It involves MRI scans to image the brain, EEG to record brain waves, EMG for muscle activity measurement, and TMS where a coil affects brain activity with electrical currents.

Group I: EEG phase-triggered PAS Experimental Treatment 1 Intervention

TMS triggered to a specific phase of the EEG mu rhythm

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

🇺🇸 Approved in United States as Transcranial Magnetic Stimulation (TMS) for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)
• Migraine Headache Symptoms

🇪🇺 Approved in European Union as Transcranial Magnetic Stimulation (TMS) for:

• Major Depressive Disorder (MDD)
• Obsessive-Compulsive Disorder (OCD)

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

National Institutes of Health Clinical Center, 9000 Rockville Pike Bethesda, MD

National Institutes of Health Clinical Center Bethesda, MD

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH) Lead Sponsor

References

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

Accelerated theta burst stimulation for the treatment of depression: A randomised controlled trial. [2022] Theta burst pattern repetitive transcranial magnetic stimulation (TBS) is increasingly applied to treat depression. TBS's brevity is well-suited to application in accelerated schedules. Sizeable trials of accelerated TBS are lacking; and optimal TBS parameters such as stimulation intensity are not established.

2. Netherlands pubmed.ncbi.nlm.nih.gov

Comparative assessment of best conventional with best theta burst repetitive transcranial magnetic stimulation protocols on human motor cortex excitability. [2008] Comparative assessment of best conventional with best theta burst repetitive transcranial magnetic stimulation (rTMS) protocols on human motor cortex excitability.

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

Dose-dependence of changes in cortical protein expression induced with repeated transcranial magnetic theta-burst stimulation in the rat. [2016] Theta Burst stimulation (TBS) applied via transcranial magnetic stimulation (TMS) effectively modulates human neocortical excitability but repeated applications of the same TBS protocol at short intervals may be not simply accumulative.

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

Efficacy and Safety of Theta Burst vs Repetitive Transcranial Magnetic Stimulation for the Treatment of Depression: A Meta-Analysis of Randomized Controlled Trials. [2023] Theta burst stimulation (TBS) is more energy- and time-efficient than is standard repetitive transcranial magnetic stimulation (rTMS). However, further studies are needed to analyze TBS therapy for its efficacy and safety compared with standard rTMS in treating depression. The aim of this meta-analysis was to compare TBS therapy with standard rTMS treatment regarding their safety and therapeutic effect on individuals with depression.

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

The Effect of Sham Controlled Continuous Theta Burst Stimulation and Low Frequency Repetitive Transcranial Magnetic Stimulation on Upper Extremity Spasticity and Functional Recovery in Chronic Ischemic Stroke Patients. [2021] This randomized controlled study examined the effect of continuous theta burst stimulation (cTBS) and low frequency repetitive transcranial magnetic stimulation (rTMS) on upper extremity spasticity and functional recovery in chronic ischemic stroke patients.

6. Switzerland pubmed.ncbi.nlm.nih.gov

Safety and tolerability of theta burst stimulation vs. single and paired pulse transcranial magnetic stimulation: a comparative study of 165 pediatric subjects. [2020] Although single- and paired-pulse (sp/pp) transcranial magnetic stimulation (TMS) studies are considered minimal risk in adults and children, the safety profile for theta-burst TMS (TBS) is unknown.

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

Safety of theta burst transcranial magnetic stimulation: a systematic review of the literature. [2022] Theta burst stimulation (TBS) protocols have recently emerged as a method to transiently alter cortical excitability in the human brain through repetitive transcranial magnetic stimulation. TBS involves applying short trains of stimuli at high frequency repeated at intervals of 200 milliseconds. Because repetitive transcranial magnetic stimulation is known to carry a risk of seizures, safety guidelines have been established. TBS has the theoretical potential of conferring an even higher risk of seizure than other repetitive transcranial magnetic stimulation protocols because it delivers high-frequency bursts. In light of the recent report of a seizure induced by TBS, the safety of this new protocol deserves consideration. We performed an English language literature search and reviewed all studies published from May 2004 to December 2009 in which TBS was applied. The adverse events were documented, and crude risk was calculated. The majority of adverse events attributed to TBS were mild and occurred in 5% of subjects. Based on this review, TBS seems to be a safe and efficacious technique. However, given its novelty, it should be applied with caution. Additionally, this review highlights the need for rigorous documentation of adverse events associated with TBS and intensity dosing studies to assess the seizure risk associated with various stimulation parameters (e.g., frequency, intensity, and location).

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

Safety Review for Clinical Application of Repetitive Transcranial Magnetic Stimulation. [2023] Studies using repetitive transcranial magnetic stimulation (rTMS) in healthy individuals and those with neuropsychiatric diseases have rapidly increased since the 1990s, due to the potential of rTMS to modulate the cortical excitability in the brain depending on the stimulation parameters; therefore, the safety considerations for rTMS use are expected to become more important. Wassermann published the first safety guidelines for rTMS from the consensus conference held in 1996, and Rossi and colleague then published the second safety guidelines from the multidisciplinary consensus meeting held in Siena, Italy in 2008, on behalf of the International Federation of Clinical Neurophysiology. More than 10 years after the second guidelines, the updated third safety guidelines were recently published in 2021. The general safety guidelines for conventional rTMS have not substantially changed. Because the most frequently used rTMS protocol is conventional (low- and high-frequency) rTMS in research and clinical settings, we focus on reviewing safety issues when applying conventional rTMS with a focal cortical stimulation coil. The following issues will be covered: 1) possible adverse events induced by rTMS; 2) checklists to screen for any precautions and risks before rTMS; 3) safety considerations for dosing conventional rTMS; and 4) safety considerations for using rTMS in stroke and traumatic brain injury.

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] 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.

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

Theta burst stimulation of the prefrontal cortex: safety and impact on cognition, mood, and resting electroencephalogram. [2009] Because standard repetitive transcranial magnetic stimulation (rTMS) protocols exhibit post-stimulus effects of short duration, novel protocols such as theta burst stimulation (TBS), are promising approaches to enhance the effectiveness of rTMS. However, little is known about the side effect profile of such protocols. Thus, the present study explores whether TBS is safe particularly in terms of effects on cognition, mood, and electroencephalogram (EEG) measures in healthy subjects.

11. Netherlands pubmed.ncbi.nlm.nih.gov

Accessory to dissipate heat from transcranial magnetic stimulation coils. [2020] Transcranial magnetic stimulation (TMS) produces magnetic pulses by passing a strong electrical current through coils of wire. Repeated stimulation accumulates heat, which places practical constraints on experimental design. New method: We designed a condensation-free pre-chilled heat sink to extend the operational duration of transcranial magnetic stimulation coils.

12. Ireland pubmed.ncbi.nlm.nih.gov

Lasting depression in corticomotor excitability associated with local scalp cooling. [2015] In this study, we investigated the effect of local scalp cooling on corticomotor excitability with transcranial magnetic simulation (TMS). Participants (healthy male adults, n=12) were first assessed with TMS to derive baseline measure of excitability from motor evoked potentials (MEPs) using the right first dorsal interosseous as the target muscle. Then, local cooling was induced on the right hemi-scalp (upper frontal region ∼ 15 cm(2)) by means of a cold wrap. The cooling was maintained for 10-15 min to get a decrease of at least 10°C from baseline temperature. In the post-cooling period, both scalp temperature and MEPs were reassessed at specific time intervals (i.e., T0, T10, T20 and T30 min). Scalp surface temperatures dropped on average by 12.5°C from baseline at T0 (p

13. Italy pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation. A case report and review of the literature. [2006] Transcranial magnetic stimulation (TMS) is a non-invasive tool for the electrical stimulation of neural tissue. TMS can be applied as single pulses of stimulation, pairs of stimuli separated by variable intervals to the same or different brain areas, or as trains of repetitive stimuli at various frequencies.

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

Multi-locus transcranial magnetic stimulation-theory and implementation. [2019] Transcranial magnetic stimulation (TMS) is a non-invasive brain stimulation method: a magnetic field pulse from a TMS coil can excite neurons in a desired location of the cortex. Conventional TMS coils cause focal stimulation underneath the coil centre; to change the location of the stimulated spot, the coil must be moved over the new target. This physical movement is inherently slow, which limits, for example, feedback-controlled stimulation.

15. Spain pubmed.ncbi.nlm.nih.gov

[Transcranial magnetic stimulation]. [2009] Transcranial magnetic stimulation (TMS) permits stimulation of the cerebral cortex in humans without requiring open access to the brain and is one of the newest tools available in neuroscience. There are two main types of application: single-pulse TMS and repetitive TMS.