Vagus Nerve Stimulation for Post-COVID Syndrome

Overseen By Anna Norweg, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Icahn School of Medicine at Mount Sinai

Disqualifiers: Bmi ≥30, Pregnancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

A prior open label study has shown that transcutaneous vagus nerve stimulation \[tVNS\] can improve the health of some patients with postacute sequelae of SARS-CoV-2 infection (PASC), severely affected enough to also fulfill criteria for myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). The purpose of this study is to compare two sets of stimulus parameters to determine the one that best improves the health-related quality of life of these patients over a period of 6-weeks. Patients using their assigned device for at least 30 of the 42 possible opportunities will receive the best device for an additional 6-week period.

Do I need to stop my current medications for the trial?

The trial information does not specify whether you need to stop taking your current medications.

Is transcutaneous vagus nerve stimulation (tVNS) safe for humans?

Transcutaneous vagus nerve stimulation (tVNS) is generally considered safe and well-tolerated in humans, including both adults and pediatric patients. Studies have shown no significant side effects, such as pain or skin irritation, and it has a good safety profile compared to invasive methods. ^{1 2 3 4 5}

How is transcutaneous vagus nerve stimulation (tVNS) different from other treatments for post-COVID syndrome?

Transcutaneous vagus nerve stimulation (tVNS) is unique because it is a non-invasive treatment that stimulates the vagus nerve through the skin of the ear, potentially reducing inflammation and improving symptoms without the need for surgery or drugs. This method is different from other treatments as it targets the nervous system directly and has been used in other conditions like epilepsy and depression, showing promise in reducing symptoms. ^{2 3 5 6 7}

What data supports the effectiveness of the treatment Transcutaneous Vagus Nerve Stimulation (tVNS) for Post-COVID Syndrome?

Research shows that transcutaneous vagus nerve stimulation (tVNS) has been beneficial in reducing inflammation and improving clinical outcomes in COVID-19 patients. Additionally, tVNS has shown positive effects in treating conditions like epilepsy and postural tachycardia syndrome, suggesting its potential for broader therapeutic applications. ^{1 5 7 8 9}

Who Is on the Research Team?

Benjamin Natelson, MD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Anna Norweg, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

This trial is for individuals who had COVID-19 and now meet the criteria for chronic fatigue syndrome (ME/CFS). They should experience significant fatigue, pain, brain fog, or worsening symptoms after exertion. It's not suitable for those who were hospitalized due to COVID-19, are pregnant, or have a BMI of 30 or more.

Inclusion Criteria

Chalder Fatigue Scale score of 4 or greater

I had COVID-19 and now meet the criteria for chronic fatigue syndrome.

My physical health limits my daily activities.

Exclusion Criteria

BMI ≥30

Pregnancy

I am hospitalized due to COVID-19.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized into Treatment A or B and use the device for 35 minutes daily over a 6-week period

6 weeks

Remote participation with device usage and questionnaires

Open-label extension

Participants who used their device for at least 30 of the 42 days receive the best device for an additional 6-week period

6 weeks

Remote participation with device usage and questionnaires

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Transcutaneous Vagus Nerve Stimulator

Trial Overview The study tests a non-invasive device called transcutaneous vagus nerve stimulator (tVNS) on patients with long-term COVID-19 effects. It aims to find out which stimulation settings improve quality of life over six weeks by comparing two different parameter sets.

How Is the Trial Designed?

Group I: #2: Device Controlled Experimental Treatment 1 Intervention

Patients will ramp up current intensity until uncomfortable, then ratchet back to what is comfortable and press button. The device has software embedded in it that is used to arrive at a personalized way of stimulating the vagus nerve. At this level, the device stimulus will not be sensed by the patient. Patient is to do this daily for 35 minutes for 6 weeks.

Group II: #1: Patient controlled Experimental Treatment 1 Intervention

Patient will ramp up current intensity until uncomfortable, then ratchet back to what is comfortable and press button. Patient is to do this daily for 35 minutes for 6 weeks.

Transcutaneous Vagus Nerve Stimulator is already approved in United States for the following indications:

Approved in United States as tVNS for:

• Postacute sequelae of SARS-CoV-2 infection (PASC)
• Myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS)

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Published Research Related to This Trial

Transcutaneous vagus nerve stimulation (tVNS) shows promise for treating various conditions in pediatric patients, but current studies lack specific protocols and justification for its use in this age group, as none of the 15 identified studies focused exclusively on children.

There are no dedicated tVNS devices for pediatric use, and existing studies do not adequately address neurodevelopmental considerations, highlighting the need for more research on age-appropriate stimulation parameters and protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters. Sigrist, C., Torki, B., Bolz, LO., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) significantly reduced levels of C-reactive protein (CRP), interleukin-6 (IL-6), and cortisol in patients with COVID-19, indicating its potential to modulate inflammation.

Patients receiving active taVNS reported greater improvements in memory and attention compared to those receiving sham stimulation, suggesting cognitive benefits, although overall clinical outcomes did not show significant differences.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation effects on inflammatory markers and clinical evolution of patients with COVID-19: a pilot randomized clinical trial. Uehara, L., Corrêa, JCF., Ritti, R., et al.[2022]

Transcutaneous vagus nerve stimulation (tVNS) significantly reduced postural tachycardia in patients with POTS, showing a mean heart rate increase of 17.6 beats/min in the active group compared to 31.7 beats/min in the sham group after 2 months.

tVNS also led to lower levels of antiadrenergic autoantibodies and inflammatory cytokines, along with improved heart rate variability, indicating its potential as a safe and effective noninvasive treatment for POTS without any reported side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial. Stavrakis, S., Chakraborty, P., Farhat, K., et al.[2023]

Transcutaneous vagus nerve stimulation (tVNS) significantly reduces seizure frequency in patients with drug-resistant epilepsy, based on a meta-analysis of three studies involving 280 patients.

tVNS appears to have a low incidence of adverse effects, with headaches being the most common, making it a safer alternative for patients who cannot undergo invasive procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation for the treatment of drug-resistant epilepsy: a meta-analysis and systematic review. Wu, K., Wang, Z., Zhang, Y., et al.[2022]

Transcutaneous vagus nerve stimulation (tVNS) was found to significantly increase salivary alpha amylase (SAA) levels and reduce the decline of salivary cortisol in healthy participants, indicating a modulation of hormonal indices related to noradrenergic function.

However, tVNS did not show any significant effects on psychophysiological measures such as P3 amplitude or pupil size, suggesting that while it may influence hormonal responses, it does not impact certain cognitive or physiological indices in the same way.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential. Warren, CM., Tona, KD., Ouwerkerk, L., et al.[2019]

Percutaneous auricular vagus nerve stimulation (aVNS) is a safe procedure for patients with severe COVID-19, with no reported side effects during or after the treatment.

While there was no significant difference in overall clinical outcomes between the aVNS and standard care groups, aVNS showed a trend towards reducing the need for invasive mechanical ventilation, suggesting potential benefits that warrant further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized controlled study to evaluate the safety and clinical impact of percutaneous auricular vagus nerve stimulation in patients with severe COVID-19. Seitz, T., Bergmayr, F., Kitzberger, R., et al.[2023]

Transcutaneous vagus nerve stimulation (tVNS) showed a significant 34% reduction in seizure frequency in patients with drug-resistant epilepsy over a 20-week trial involving 39 participants, compared to a 2.9% reduction in the control group.

The tVNS method was well-tolerated by participants, suggesting it is a safe alternative to surgical implantation for vagus nerve stimulation, warranting further research with longer observation periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lessons learned from transcutaneous vagus nerve stimulation (tVNS). Hamer, HM., Bauer, S.[2019]

Transcutaneous vagus nerve stimulation (tVNS) significantly improved sleep quality and reduced anxiety in 100 patients with insomnia at high altitude, as measured by the Pittsburgh Sleep Quality Index and other scales after 4 weeks of treatment.

Polysomnography results showed that tVNS led to shorter sleep latency and longer periods of deep sleep, indicating its potential effectiveness as a treatment for insomnia in challenging environments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous Vagus Nerve Stimulation for Insomnia in People Living in Places or Cities with High Altitudes: A Randomized Controlled Trial. Zhang, L., Jin, Y., Zhang, Q., et al.[2023]

A pilot study involving 24 patients with chronic tinnitus demonstrated that transcutaneous vagus nerve stimulation (tVNS) is a feasible and generally safe treatment method, with only two adverse cardiac events reported, which were unlikely linked to the device.

Preliminary data suggest that tVNS does not cause arrhythmic effects in patients without known heart conditions, indicating its potential safety for cardiac function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation: retrospective assessment of cardiac safety in a pilot study. Kreuzer, PM., Landgrebe, M., Husser, O., et al.[2022]

Citations

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

Transcutaneous Auricular Vagus Nerve Stimulation in Pediatric Patients: A Systematic Review of Clinical Treatment Protocols and Stimulation Parameters. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Transcutaneous auricular vagus nerve stimulation effects on inflammatory markers and clinical evolution of patients with COVID-19: a pilot randomized clinical trial. [2022]

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

Noninvasive Vagus Nerve Stimulation in Postural Tachycardia Syndrome: A Randomized Clinical Trial. [2023]

4. Australia pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation for the treatment of drug-resistant epilepsy: a meta-analysis and systematic review. [2022]

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

The neuromodulatory and hormonal effects of transcutaneous vagus nerve stimulation as evidenced by salivary alpha amylase, salivary cortisol, pupil diameter, and the P3 event-related potential. [2019]

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

Randomized controlled study to evaluate the safety and clinical impact of percutaneous auricular vagus nerve stimulation in patients with severe COVID-19. [2023]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Lessons learned from transcutaneous vagus nerve stimulation (tVNS). [2019]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous Vagus Nerve Stimulation for Insomnia in People Living in Places or Cities with High Altitudes: A Randomized Controlled Trial. [2023]

9. Switzerland pubmed.ncbi.nlm.nih.gov

Transcutaneous vagus nerve stimulation: retrospective assessment of cardiac safety in a pilot study. [2022]