Transcranial Magnetic Stimulation for Anesthesia Recovery

(REDEX Trial)

Overseen By David Schreier, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Massachusetts General Hospital

Must not be taking: Stimulants, Anticoagulants

Disqualifiers: Epilepsy, Hypertension, Asthma, Diabetes, 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: 1

Duration: Up to 120 minutes

12 Participants Needed

Trial Summary

What is the purpose of this trial?

This pilot study in healthy volunteers aims to determine if biological sex has an impact on recovery from dexmedetomidine-induced unconsciousness, and if transcranial magnetic stimulation combined with electroencephalography (TMS-EEG) can be used to measure brain complexity during dexmedetomidine sedation without arousing study participants.

Will I have to stop taking my current medications?

Yes, you will need to stop taking any regular medications that affect central nervous function, as well as anticoagulant or blood-thinning medications. However, oral hormonal contraception is allowed.

What data supports the effectiveness of the treatment Transcranial Magnetic Stimulation for anesthesia recovery?

Research shows that repetitive transcranial magnetic stimulation (rTMS) can help improve attention in Alzheimer's patients and relieve neuropathic pain, suggesting it can positively affect brain function. Additionally, rTMS has been shown to protect brain cells from damage after a lack of blood flow, indicating its potential to aid in recovery processes. ^{1 2 3 4 5}

Is transcranial magnetic stimulation (TMS) safe for humans?

Transcranial magnetic stimulation (TMS) is generally considered safe, but it can cause seizures in rare cases. Safety guidelines have been developed to minimize risks, and most studies focus on ensuring safe use, especially in clinical settings. ^{6 7 8 9 10}

How does the treatment Transcranial Magnetic Stimulation (rTMS) for anesthesia recovery differ from other treatments?

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, unlike traditional drug-based treatments. It is known for its ability to modulate brain activity and has been used for conditions like depression and movement disorders, making it a novel approach for aiding anesthesia recovery. ^{2 5 11 12 13}

Research Team

Ken Solt, MD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for healthy, non-smoking adults aged 18-45 with a BMI of 18 to 30. Participants must not have a history of stimulant or substance abuse, be in good health (ASA 1), speak English fluently, and women must use hormonal contraception.

Inclusion Criteria

Non-smoker

I am in good health with no physical limitations.

My BMI is between 18 and 30.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive dexmedetomidine sedation and undergo TMS-EEG or no intervention

Up to 120 minutes

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Transcranial Magnetic Stimulation

Trial Overview The study tests if biological sex affects recovery from unconsciousness induced by dexmedetomidine. It also examines whether transcranial magnetic stimulation (TMS) alongside EEG can measure brain activity during sedation without waking participants.

Participant Groups

Group I: TMS-EEG Arm Experimental Treatment 1 Intervention

This arm will undergo TMS-EEG during the study.

Group II: Non-TMS-EEG Arm Active Control 1 Intervention

This arm will not undergo TMS-EEG during the study.

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?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Findings from Research

Repetitive transcranial magnetic stimulation (rTMS) applied to the M1/S1 cortex significantly lowers μ-opioid receptor availability, indicating the release of endogenous opioids in various brain regions associated with pain processing, which may contribute to its pain-relieving effects.

Despite the activation of the endogenous opioid system, rTMS did not change thermal pain thresholds or sensory discrimination of painful stimuli, suggesting that while rTMS enhances opioid-mediated inhibition, it does not alter the perception of pain intensity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neurotransmitters behind pain relief with transcranial magnetic stimulation - positron emission tomography evidence for release of endogenous opioids. Lamusuo, S., Hirvonen, J., Lindholm, P., et al.[2018]

In a pilot study involving 10 patients with mild cognitive impairment or early dementia, high-frequency rTMS applied to the right inferior frontal gyrus significantly improved attention and psychomotor speed, as measured by the Trail Making Test.

No cognitive improvements were observed with rTMS applied to a control site (vertex), suggesting that targeted stimulation of the right IFG may be an effective intervention for enhancing cognitive functions in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Non-invasive brain stimulation of the right inferior frontal gyrus may improve attention in early Alzheimer's disease: a pilot study. Eliasova, I., Anderkova, L., Marecek, R., et al.[2022]

In anesthetized cats, high-frequency repetitive transcranial magnetic stimulation (HF rTMS) significantly increased glucose uptake in the targeted visuo-parietal cortex after stimulation, indicating a lasting effect on cortical excitability, while low-frequency rTMS (LF rTMS) had the opposite effect.

The study highlights that the effects of rTMS on brain activity can vary based on the frequency of stimulation, with HF rTMS enhancing local activity and LF rTMS reducing it, supporting the potential of rTMS for neuromodulation in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Opposite impact on 14C-2-deoxyglucose brain metabolism following patterns of high and low frequency repetitive transcranial magnetic stimulation in the posterior parietal cortex. Valero-Cabré, A., Payne, BR., Pascual-Leone, A.[2022]

Active 1-Hz repetitive transcranial magnetic stimulation (rTMS) of the primary motor area (M1) not only decreases excitability in the stimulated hemisphere but also reduces excitability in the contralateral hemisphere, indicating a bilateral effect.

The study shows that rTMS can condition cortical excitability even at a distance, suggesting that decreased excitability may be linked to reduced blood flow and metabolism in the brain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Crossed reduction of human motor cortex excitability by 1-Hz transcranial magnetic stimulation. Wassermann, EM., Wedegaertner, FR., Ziemann, U., et al.[2019]

Repetitive transcranial magnetic stimulation (rTMS) can protect hippocampal neurons from delayed neuronal death after a lethal ischemic event, with the most effective timing being 2 to 5 days before the ischemic insult.

The study found that rTMS delivered at 25 Hz for 128 seconds was more effective in preserving neuron density compared to higher frequency stimulation, highlighting its potential as a noninvasive method to prevent ischemic neuronal damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation for protection against delayed neuronal death induced by transient ischemia. Fujiki, M., Kobayashi, H., Abe, T., et al.[2022]

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]

Transcranial magnetic stimulation (TMS) has a very low seizure risk, with only 0.08 seizures reported per 1,000 sessions, and less than 0.02 seizures per 1,000 sessions when guidelines are followed for individuals without known risk factors.

The study found that exceeding safety guidelines increases the risk of seizures, and seizures are more likely to occur during the first few TMS sessions, suggesting that TMS is generally safe when administered properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. Lerner, AJ., Wassermann, EM., Tamir, DI.[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]

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]

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]

Suprathreshold rTMS over the left primary sensorimotor cortex significantly increased brain activity in the stimulated area and supplementary motor area (SMA) in most subjects, indicating effective neuronal activation.

Subthreshold rTMS did not activate the primary sensorimotor cortex but still modulated activity in remote areas like the SMA and lateral premotor cortex, suggesting it influences corticocortical connections without inducing motor responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subthreshold high-frequency TMS of human primary motor cortex modulates interconnected frontal motor areas as detected by interleaved fMRI-TMS. Bestmann, S., Baudewig, J., Siebner, HR., et al.[2019]

This trial will evaluate whether a 1-week accelerated rTMS treatment is as effective as the standard 4-week treatment for depression, involving 60 patients over a 2-year period.

The study aims to determine if additional accelerated rTMS treatments can benefit patients who do not respond to initial therapy, potentially optimizing treatment strategies for depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Accelerated transcranial magnetic stimulation (aTMS) to treat depression with treatment switching: study protocol of a pilot, randomized, delayed-start trial. Tan, XW., Abdin, E., Tor, PC.[2021]

References

1. England pubmed.ncbi.nlm.nih.gov

Neurotransmitters behind pain relief with transcranial magnetic stimulation - positron emission tomography evidence for release of endogenous opioids. [2018]

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

Non-invasive brain stimulation of the right inferior frontal gyrus may improve attention in early Alzheimer's disease: a pilot study. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Opposite impact on 14C-2-deoxyglucose brain metabolism following patterns of high and low frequency repetitive transcranial magnetic stimulation in the posterior parietal cortex. [2022]

4. Ireland pubmed.ncbi.nlm.nih.gov

Crossed reduction of human motor cortex excitability by 1-Hz transcranial magnetic stimulation. [2019]

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

Repetitive transcranial magnetic stimulation for protection against delayed neuronal death induced by transient ischemia. [2022]

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

Side effects of repetitive transcranial magnetic stimulation. [2005]

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

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

8. Netherlands pubmed.ncbi.nlm.nih.gov

Seizures from transcranial magnetic stimulation 2012-2016: Results of a survey of active laboratories and clinics. [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. United States 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. [2022]

11. Germany pubmed.ncbi.nlm.nih.gov

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

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

Subthreshold high-frequency TMS of human primary motor cortex modulates interconnected frontal motor areas as detected by interleaved fMRI-TMS. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Accelerated transcranial magnetic stimulation (aTMS) to treat depression with treatment switching: study protocol of a pilot, randomized, delayed-start trial. [2021]