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

Trial Summary

What is the purpose of this trial?

The purpose of this study is to test if Variable Pulse TMS (Transcranial Magnetic Stimulation) can result in objective improvements in patients with Post COVID Syndrome (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 data supports the effectiveness of the treatment Electromagnetic Brain Pulsing Variable Pulse Protocol (EMBP) for Post-COVID Syndrome?

A case report showed that a patient with long-COVID symptoms, including breathing difficulties, loss of smell, and cognitive issues, experienced improvements after 10 sessions of EMBP treatment. The patient had better mood, sense of smell, and cognitive function, along with improved breathing capacity. ^{1 2 3 4 5}

Is transcranial magnetic stimulation safe for humans?

Transcranial magnetic stimulation (TMS) is generally considered safe for humans, with studies showing it is well-tolerated in conditions like mild traumatic brain injury and post-concussion symptoms. Some common side effects include headaches and sleep disturbances, but these are usually mild and temporary. ^{1 2 6 7 8}

How is the treatment Transcranial Magnetic Stimulation for Post-COVID Syndrome unique?

This treatment is unique because it uses a personalized transcranial magnetic stimulation protocol guided by the patient's brain activity (EEG), which is noninvasive and has shown early success in improving symptoms like brain fog, mood, and sense of smell in long-COVID patients. ^{1 2 5 9 10}

Research Team

Ryan T. Hurt, M.D.

Principal Investigator

Mayo Clinic

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2023]

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

Left Dorsolateral Prefrontal Cortex rTMS in Alleviating MTBI Related Headaches and Depressive Symptoms. [2022]

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

Noninvasive Transcranial Magnetic Brain Stimulation in Stroke. [2019]

4. England pubmed.ncbi.nlm.nih.gov

fMRI findings in MTBI patients with headaches following rTMS. [2022]

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

Safety and behavioral effects of high-frequency repetitive transcranial magnetic stimulation in stroke. [2018]

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

Noninvasive brain stimulation for persistent postconcussion symptoms in mild traumatic brain injury. [2022]

7. United States 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. [2022]

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

Repetitive Transcranial Magnetic Stimulation in Managing Mild Traumatic Brain Injury-Related Headaches. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Effects of transcranial magnetic stimulation in modulating cortical excitability in patients with stroke: a systematic review and meta-analysis. [2022]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Transcranial magnetic stimulation in clinical practice. [2018]