rTMS for Post-COVID Syndrome

Overseen By Courtney Sheen, MA

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Must be taking: Psychotropic medications

Must not be taking: Clozaril, Wellbutrin

Disqualifiers: Bipolar, Schizophrenia, Alcohol abuse, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a treatment called rTMS, a type of brain stimulation, to help people with Long-COVID experiencing fatigue and brain fog. Participants will receive either real rTMS or a placebo treatment to assess the effectiveness and safety of rTMS in easing these symptoms. Ideal candidates have had COVID-19 confirmed by a PCR test and are now dealing with ongoing tiredness and mental cloudiness. As an unphased trial, this study offers participants the chance to contribute to groundbreaking research that could lead to new treatments for Long-COVID symptoms.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you must have been stable on psychotropic medications for at least 4 months, and as-needed use of benzodiazepines and beta-blockers is allowed but discouraged during assessment days.

What prior data suggests that rTMS is safe for treating Long-COVID symptoms?

Research shows that repetitive transcranial magnetic stimulation (rTMS) is generally safe for treating brain-related symptoms. Studies have investigated its use for Long-COVID patients and found it well-tolerated. In one study, participants experienced few side effects, which were mild, such as headaches or slight scalp discomfort.

Another study confirmed that rTMS is safe and effective for symptoms like brain fog and mood changes. Multiple reviews and case series support the safety of rTMS, showing it did not cause any serious side effects. Overall, the data suggest that rTMS is a promising option for managing Long-COVID symptoms, with a good safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about rTMS for post-COVID syndrome because it offers a new, non-invasive way to potentially improve symptoms that other treatments, like medications or physical therapy, haven't fully addressed. Unlike standard treatments that often target symptoms broadly, rTMS specifically uses magnetic fields to stimulate precise areas of the brain, like the left dorsolateral prefrontal cortex and left primary motor cortex, which could lead to more targeted and effective relief. This technique could be especially beneficial for patients who haven't responded well to existing options, providing a fresh approach with potentially fewer side effects.

What evidence suggests that rTMS might be an effective treatment for Long-COVID?

Research has shown that repetitive transcranial magnetic stimulation (rTMS) may help alleviate Long-COVID symptoms such as brain fog and mood issues. Studies have found that rTMS can enhance cognitive abilities and reduce fatigue in patients experiencing ongoing effects from COVID-19. Specifically, one study noted that participants experienced clearer thinking and more stable moods following rTMS treatment. Another review suggested that rTMS could be beneficial for treating various mental health symptoms associated with post-COVID conditions. In this trial, participants will receive either active rTMS or sham rTMS to assess its effectiveness. Overall, early evidence indicates that rTMS might be a promising option for managing Long-COVID symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

Helen Lavretsky, MD

Principal Investigator

University of California, Los Angeles

Are You a Good Fit for This Trial?

This trial is for individuals with Long-COVID experiencing fatigue, brain fog, and other neuropsychiatric symptoms. Participants will be selected from the UCLA Long-COVID clinic. Specific eligibility criteria are not provided but typically include a confirmed diagnosis of Long-COVID and meeting certain health standards.

Inclusion Criteria

I am taking medication for my mental health.

Subjects are willing and able to adhere to the treatment schedule and required study visits

I experience fatigue and brain fog due to recent neuropsychiatric symptoms.

Exclusion Criteria

Presence of an implanted metallic and magnetic-sensitive medical device present in the body scan, including but not limited to a cochlear implant, infusion pump, implanted cardioverter defibrillator, pacemaker, vagus nerve stimulator, aneurysm clip, metal prosthesis, or metal aneurysm clips or coils, staples, or stents

I am unable to understand or sign the consent form due to mental or legal reasons.

My cognitive function test score is 24 or less.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 15 treatments of either active rTMS or sham stimulation, followed by another 15 open-label rTMS treatments

12 weeks

15 visits (in-person) for each treatment phase

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension

Participants receive an additional 15 open-label rTMS treatments

6 weeks

What Are the Treatments Tested in This Trial?

Interventions

• rTMS

Trial Overview

The study tests rTMS (repetitive Transcranial Magnetic Stimulation) against sham stimulation in patients with Long-COVID. It involves 15 treatments of either real or placebo rTMS followed by another 15 open-label treatments to assess changes in various symptoms like fatigue and cognitive impairment.

How Is the Trial Designed?

Group I: active rTMS Active Control 1 Intervention

The rTMS magnet will be set to active stimulation without the knowledge of treating doctors or research team. Only one technician will know the randomization list assignment and will adjust the settings. rTMS treatment will include rTMS to the left dorsolateral prefrontal cortex (DLPFC), followed by rTMS to left primary motor cortex (M1).

Group II: Sham rTMS Placebo Group 1 Intervention

The rTMS magnet will be set to sham stimulation without the knowledge of the treating doctors or the research team.

rTMS is already approved in United States, European Union for the following indications:

Approved in United States as rTMS for:

• Obsessive-Compulsive Disorder (OCD)
• Major Depressive Disorder
• Migraines
• Smoking cessation

Approved in European Union as rTMS for:

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

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

Published Research Related to This Trial

In a 6-month follow-up study of 31 patients with major depression who completed a 4-week rTMS trial, 63.64% of those who initially did not respond to treatment became late responders, indicating potential for continued improvement after treatment ends.

The study also found a low relapse rate of only 10% among those who initially responded to rTMS, with an overall high rate of maintained response at 90%, suggesting that rTMS can have lasting effects in treating major depression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A 6-month follow-up study on response and relapse rates following an acute trial of repetitive transcranial magnetic stimulation in patients with major depression. Arici, C., Benatti, B., Cafaro, R., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) shows variable effects on corticospinal pathway excitability in healthy adults, with different frequencies producing different outcomes, indicating that the optimal parameters for rTMS are not yet established.

In stroke patients, there is a trend suggesting that 10 sessions of 3 Hz rTMS may aid in the recovery of motor-evoked potentials, but overall evidence is insufficient to determine effective dosing for improving motor function in paretic limbs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Informing dose-finding studies of repetitive transcranial magnetic stimulation to enhance motor function: a qualitative systematic review. Hiscock, A., Miller, S., Rothwell, J., et al.[2018]

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 safe and effective therapy for post-stroke rehabilitation, enhancing neuroplasticity and helping patients recover motor skills and cognitive functions.

rTMS can optimize brain activity by applying targeted electromagnetic pulses to specific brain regions, leading to improvements in various stroke-related complications such as motor disorders, aphasia, and depression, although more extensive clinical trials are needed for broader recommendations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current evidence on transcranial magnetic stimulation and its potential usefulness in post-stroke neurorehabilitation: Opening new doors to the treatment of cerebrovascular disease. León Ruiz, M., Rodríguez Sarasa, ML., Sanjuán Rodríguez, L., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) significantly improves upper limb function, hand function, and muscle tone in chronic stroke patients (≥6 months post-stroke), based on a meta-analysis of 25 randomized controlled trials involving 535 participants.

rTMS also positively impacts cognitive performance and reduces apathy in stroke patients, although it does not significantly improve lower limb mobility and strength.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of repetitive transcranial magnetic stimulation on sequelae in patients with chronic stroke: A systematic review and meta-analysis of randomized controlled trials. Chen, G., Wu, M., Lin, 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]

Transcranial magnetic stimulation (TMS) significantly improved psychiatric symptoms such as depression, anxiety, and insomnia in patients suffering from Long-COVID and Post-Vaccine conditions, based on a retrospective analysis of 60 patients.

The effectiveness of TMS in alleviating depression was found to decrease with higher levels of fatigue, indicating that fatigue may be a limiting factor in treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fatigue Potentially Reduces the Effect of Transcranial Magnetic Stimulation on Depression Following COVID-19 and Its Vaccination. Kamamuta, A., Takagi, Y., Takahashi, M., et al.[2023]

A 75-year-old man experienced reversible cerebral vasoconstriction syndrome (RCVS) after undergoing low-frequency repetitive transcranial magnetic stimulation (rTMS) combined with occupational therapy, marking the first reported case of RCVS triggered by rTMS.

Despite the occurrence of RCVS, the study concluded that rTMS remains a safe rehabilitation treatment, although clinicians should be aware of the potential for RCVS as a complication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A case of cerebral reversible vasoconstriction syndrome triggered by repetition transcranial magnetic stimulation. Sato, M., Yamate, K., Hayashi, H., et al.[2017]

Repetitive transcranial magnetic stimulation (rTMS) can enhance brain plasticity and has shown promise in improving motor recovery when applied in the early weeks following a stroke, as opposed to months or years later.

Clinical studies indicate that early rTMS treatment can lead to sustained improvements in grip strength and upper extremity motor function, suggesting its potential as a beneficial intervention shortly after a stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation for Upper Extremity Motor Recovery: Does It Help? Schambra, HM.[2020]

Repetitive Transcranial Magnetic Stimulation (rTMS) is effective in improving upper limb motor function in individuals with subacute and chronic stroke, based on a review of 32 studies involving 1137 participants.

The effectiveness of rTMS protocols varies, but combining rTMS with physical rehabilitation leads to better outcomes, suggesting that tailored treatment approaches may enhance recovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive transcranial magnetic stimulation of primary motor cortex for stroke upper limb motor sequelae rehabilitation: A systematic review. Sánchez-Cuesta, FJ., González-Zamorano, Y., Arroyo-Ferrer, A., et al.[2023]

In a pilot study involving 28 patients with treatment-resistant depression (TRD), accelerated deep transcranial magnetic stimulation (adTMS) showed significant reductions in depression scores, with a 59% decrease in Hamilton Depression Rating Scale (HDRS) scores after 10 days and 62% after 15 days.

The treatment was found to be safe, with only 9% of patients discontinuing due to adverse events, and 38% to 42% of patients achieving remission, indicating that adTMS could provide rapid clinical benefits and warrants further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot investigation of accelerated deep transcranial magnetic stimulation protocols in treatment-resistant depression. Filipčić, I., Šimunović Filipčić, I., Sučić, S., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) can effectively improve cognitive function and behavioral symptoms in dementia patients, as demonstrated in a case where a patient showed significant improvement after switching from 1 Hz to 10 Hz rTMS.

While rTMS is generally beneficial, it can lead to adverse reactions such as seizures; however, adjusting the treatment parameters (like reducing the frequency) can help mitigate these risks and continue to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The repetitive transcranial magnetic stimulation in Alzheimer's disease patients with behavioral and psychological symptoms of dementia: a case report. Yang, Z., Zhou, Y.[2023]

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