Transcranial Magnetic Stimulation for Post-COVID Syndrome

Overseen By Department of Medicine Research Hub, Coordinator

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Mayo Clinic

Disqualifiers: Seizure history, Stroke, Pregnancy, others

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

Compensation: Varies

Number of Visits: 14

Duration: 12 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment for Post-COVID Syndrome (PCS) using Transcranial Magnetic Stimulation, which sends magnetic pulses to the brain. The goal is to determine if this method, specifically the Electromagnetic Brain Pulsing Variable Pulse Protocol (EMBP), can help alleviate ongoing symptoms such as severe fatigue, tinnitus (ringing in the ears), or anosmia (loss of smell). Individuals who have had COVID-19 and continue to experience one of these symptoms at least a month after infection may be suitable for this trial. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could lead to new treatments for PCS.

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's best to discuss this with the trial team or your doctor.

What prior data suggests that this protocol is safe for Post-COVID Syndrome?

Research has shown that Transcranial Magnetic Stimulation (TMS) is generally safe. Studies have found that TMS rarely causes serious side effects. Some individuals might experience mild discomfort or headaches during or after treatment, but these effects are typically temporary.

The Electromagnetic Brain Pulsing (EMBP) method employs a specialized form of TMS. Researchers have studied this method for treating Post-COVID Syndrome symptoms, such as fatigue, tinnitus, and anosmia. Reviews suggest that this treatment is safe, with very few negative effects reported.

Safety data for TMS in similar conditions supports its use. Prospective clinical trial participants should consult the study team for more personalized information. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcranial Magnetic Stimulation (TMS) for post-COVID syndrome because it offers a new approach to tackling symptoms like fatigue, tinnitus, and anosmia. Unlike conventional treatments, which often involve medications that manage symptoms, TMS uses electromagnetic brain pulsing to potentially alter brain activity directly. This non-invasive method targets specific brain areas thought to be affected by post-COVID syndrome, which could lead to more effective and quicker relief. Additionally, TMS is a drug-free option, reducing the risk of medication-related side effects.

What evidence suggests that this protocol is effective for Post-COVID Syndrome?

Research has shown that Transcranial Magnetic Stimulation (TMS) can alleviate symptoms of Post-COVID Syndrome (PCS). Studies have found improvements in fatigue, cognitive function, and mood with TMS. In one case, a patient reported feeling happier, experiencing a better sense of smell, and having less mental fog. The treatment also appeared to enhance sleep and overall quality of life. This trial will examine the effects of TMS on specific PCS symptoms, with different treatment arms focusing on fatigue, tinnitus, and anosmia. Although more research is needed, these early findings suggest that TMS might effectively treat PCS symptoms such as tiredness, ringing in the ears, and loss of smell. ^{1 2 5 6 7}

Who Is on the Research Team?

Ryan T. Hurt, M.D.

Principal Investigator

Mayo Clinic

Are You a Good Fit for This Trial?

This trial is for individuals experiencing lingering symptoms after recovering from COVID-19, known as Post-COVID Syndrome. Specific eligibility criteria are not provided.

Inclusion Criteria

I've had symptoms for more than 4 weeks after getting COVID.

I have lost my sense of smell, experience ringing in my ears, or feel very tired since having COVID-19.

I had COVID-19 and have been experiencing loss of smell, ringing in the ears, or fatigue for over a month.

Exclusion Criteria

I am able to understand and sign the informed consent.

Active alcohol abuse: >14 drinks a week or formal diagnosis, illicit drug use or drug abuse

Intracranial implant within 30 cm of magnet or any other metal object within or near the head, excluding the mouth, which cannot be safely removed

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Variable Pulse Transcranial Magnetic Stimulation (TMS) for Post COVID Syndrome

12 weeks

Regular visits at baseline, 2 weeks, 4 weeks, 10 weeks, and 12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

Follow-up assessments at 12 weeks

Long-term monitoring

Monitoring for serious adverse events (SAEs) throughout the study duration

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Electromagnetic Brain Pulsing Variable Pulse Protocol (EMBP)

Trial Overview The study is testing a treatment called Variable Pulse Transcranial Magnetic Stimulation (TMS) over two different durations: one group for 2 weeks and another for 4 weeks, to see if it can improve PCS symptoms.

How Is the Trial Designed?

Group I: Tinnitus Experimental Treatment 1 Intervention

Subjects have \>0 score on Tinnitus Handicap Inventory (not present prior to COVID infection)

Group II: Fatigue Experimental Treatment 1 Intervention

Subjects have Total Modified Fatigue Impact Scale (MFIS) Score of 40 or above

Group III: Anosmia Experimental Treatment 1 Intervention

Subjects Olfactory Threshold Test scores correspond to Anosmia or Hyposmia

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Repetitive transcranial magnetic stimulation (rTMS) at the left prefrontal cortex significantly reduced headache intensity in veterans with persistent mild traumatic brain injury-related headaches (MTBI-HA), with a 25.3% reduction at one week and 23.0% at four weeks post-treatment compared to a sham group.

The rTMS treatment also led to a notable improvement in depressive symptoms, as measured by the Hamilton Rating Scale for Depression, indicating potential mood-enhancing benefits alongside headache relief.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Left Dorsolateral Prefrontal Cortex rTMS in Alleviating MTBI Related Headaches and Depressive Symptoms. Leung, A., Metzger-Smith, V., He, Y., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) and theta burst stimulation (TBS) have been shown to effectively modulate cortical excitability in stroke patients, with low frequency rTMS decreasing resting motor thresholds and increasing motor-evoked potentials in the affected brain area.

High frequency rTMS and intermittent TBS specifically enhance cortical excitability in the affected motor area, suggesting these protocols can aid in motor recovery after a stroke, while the effects of continuous TBS remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of transcranial magnetic stimulation in modulating cortical excitability in patients with stroke: a systematic review and meta-analysis. Bai, Z., Zhang, J., Fong, KNK.[2022]

Transcranial magnetic stimulation (TMS) is a non-invasive and painless method used since 1985 to stimulate the brain and cranial nerves, with applications in both diagnostics and treatment.

Repetitive TMS can modify the excitability of the cerebral cortex, making it a promising therapeutic tool for investigating neural circuitry and treating various neurological conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in clinical practice. Alisauskiene, M., Truffert, A., Vaiciene, N., et al.[2018]

In a study involving 7 participants with disordered consciousness after severe traumatic brain injury, repetitive transcranial magnetic stimulation (rTMS) was found to have a relatively safe profile, with only 75 mild nonserious adverse events and 1 serious adverse event (a seizure).

Despite the potential for seizure induction, the study suggests that rTMS can be safely administered to this vulnerable population, indicating that future research could include a broader range of patients who were previously excluded due to safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Considerations for the Use of Transcranial Magnetic Stimulation as Treatment for Coma Recovery in People With Severe Traumatic Brain Injury. Kletzel, SL., Aaronson, AL., Guernon, A., et al.[2022]

In a study involving 26 participants with mild traumatic brain injury (MTBI) and persistent headaches, real repetitive transcranial magnetic stimulation (rTMS) significantly reduced headache frequency and intensity one week after treatment, while sham treatment showed no such effects.

fMRI results indicated that real rTMS enhanced functional connectivity in the left prefrontal cortex, which is crucial for pain modulation, suggesting that rTMS may improve the brain's ability to manage pain in MTBI patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

fMRI findings in MTBI patients with headaches following rTMS. Vaninetti, M., Lim, M., Khalaf, A., et al.[2022]

Repetitive transcranial magnetic stimulation (rTMS) significantly reduced headache intensity in veterans with mild traumatic brain injury (MTBI), with a 56.3% reduction in the REAL group compared to 15.4% in the SHAM group after one week.

The treatment was clinically feasible and effective, with 58.3% of the REAL group experiencing at least a 50% reduction in headache intensity, and a significant decrease in overall headache-related disability observed at the four-week assessment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Repetitive Transcranial Magnetic Stimulation in Managing Mild Traumatic Brain Injury-Related Headaches. Leung, A., Shukla, S., Fallah, A., et al.[2022]

A 36-year-old male with long-COVID symptoms showed significant improvement in mood, sense of smell, and cognitive function after 10 sessions of personalized transcranial magnetic stimulation (EMBP®), indicating potential efficacy of this treatment for long-COVID.

Post-treatment assessments revealed a notable increase in forced expiratory volume and cognitive test scores, along with EEG changes suggesting enhanced brain activity, highlighting the need for further research into noninvasive brain stimulation techniques for long-COVID symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case Report of Improvement in Long-COVID Symptoms in an Air Force Medic Treated With Transcranial Magnetic Stimulation Using Electro-Magnetic Brain Pulse Technique. Zhang, JX., Zhang, JJ.[2023]

In a study involving 12 patients with chronic stroke, high-frequency repetitive transcranial magnetic stimulation (rTMS) was found to be safe, with no new symptoms reported and only a modest increase in systolic blood pressure.

Patients showed modest improvements in motor function, such as grip strength and range of motion, particularly in younger individuals, suggesting potential benefits of rTMS for reducing motor deficits after stroke.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and behavioral effects of high-frequency repetitive transcranial magnetic stimulation in stroke. Yozbatiran, N., Alonso-Alonso, M., See, J., et al.[2018]

Repetitive transcranial magnetic stimulation (rTMS) targeting the left dorsolateral prefrontal cortex (DLPFC) is safe and well-tolerated in patients with persistent postconcussive symptoms (PCS) following mild traumatic brain injury (mTBI), with 12 out of 15 participants completing the treatment protocol.

The treatment resulted in a significant reduction in PCS severity, with an average decline of 14.6 points on the PCS Scale, and increased brain activation in the DLPFC during cognitive tasks, suggesting rTMS may effectively alleviate symptoms associated with mTBI.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive brain stimulation for persistent postconcussion symptoms in mild traumatic brain injury. Koski, L., Kolivakis, T., Yu, C., et al.[2022]

Transcranial magnetic brain stimulation shows promise as a future treatment for stroke and related impairments, with varying targets and stimulation parameters depending on the specific issue being addressed, such as weakness or cognitive dysfunction.

Identifying biomarkers could help determine which patients are most likely to benefit from this treatment, and combining it with medications or targeted exercises may enhance its effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Transcranial Magnetic Brain Stimulation in Stroke. Hernandez-Pavon, JC., Harvey, RL.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06865222

Post COVID-19 Syndrome Treatment With Variable Pulse ... The purpose of this study is to test if Variable Pulse TMS (Transcranial Magnetic Stimulation) can result in objective improvements in patients with Post ...

2. amjmed.com amjmed.com/article/S0002-9343(24)00468-6/fulltext

Non-Invasive Brain Stimulation for Post-COVID-19 ... Existing studies report first promising results, illustrating improvement in clinical outcome parameters. Yet, the mechanistic understanding of ...

3. medrxiv.org medrxiv.org/content/10.1101/2025.06.05.25329096.full

Therapeutic Potential of Transcranial Magnetic Stimulation ... Key outcomes include fatigue, cognitive function, mood/psychological symptoms, sleep disturbances, quality of life, and overall symptom ...

4. embp.com.tw embp.com.tw/news-detail.php?id=200&lang=en

Mayo Clinic Research on the Effects of EMBP on Post-COVID ... Mayo Clinic is conducting a clinical study to evaluate whether EMBP technology can provide objective improvements for PCS patients.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37267198/

Case Report of Improvement in Long-COVID Symptoms ... At the conclusion of the treatment, the patient had improvements in mood, sense of smell, and brain fogging. Dyspnea also decreased with a gain ...

6. mayo.edu mayo.edu/research/clinical-trials/cls-20574138

Post COVID Syndrome Treatment With Variable Pulse ... The purpose of this study is to test if Variable Pulse TMS (Transcranial Magnetic Stimulation) can result in objective improvements in patients ...

7. ctv.veeva.com ctv.veeva.com/study/post-covid-19-syndrome-treatment-with-variable-pulse-transcranial-magnetic-stimulation

Post COVID-19 Syndrome Treatment With Variable Pulse ... The purpose of this study is to test if Variable Pulse TMS (Transcranial Magnetic Stimulation) can result in objective improvements in patients ...