Vagus Nerve Stimulation for Post-COVID Syndrome

Overseen By David Putrino

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Icahn School of Medicine at Mount Sinai

Disqualifiers: Pregnancy, Cardiac disease, Bradycardia, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

40 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial will test a portable device that sends gentle electrical pulses to a nerve in the neck to help people with Long COVID. The goal is to see if this can reduce their symptoms by calming their body's stress response.

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. Please consult with the study coordinators for more details.

Is vagus nerve stimulation safe for humans?

Vagus nerve stimulation, especially the non-invasive type, is generally considered safe for humans. Common mild side effects include ear pain, headache, and tingling, but serious side effects are rare. Studies have shown it to be safe in various conditions, including severe COVID-19, with no significant adverse effects reported. ^{1 2 3 4 5}

How does non-invasive vagus nerve stimulation differ from other treatments for post-COVID syndrome?

Non-invasive vagus nerve stimulation (nVNS) is unique because it targets the vagus nerve to reduce inflammation and improve respiratory symptoms without the need for drugs. This treatment is administered through the skin, often using electrodes on the ear, and is designed to modulate the body's immune response, which is different from standard treatments that may focus on directly targeting the virus or symptoms. ^{2 3 6 7 8}

What data supports the effectiveness of the treatment Non-invasive vagus nerve stimulation for Post-COVID Syndrome?

Research suggests that non-invasive vagus nerve stimulation (nVNS) may help reduce inflammation, which is a key issue in severe COVID-19 cases. Studies have shown that nVNS can potentially decrease the need for invasive ventilation in severe COVID-19 patients and may have mild to moderate effects in reducing long COVID symptoms like mental fatigue. ^{2 3 8 9 10}

Research Team

David Putrino, PT, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Eligibility Criteria

This trial is for adults over 18 who have developed dysautonomia after COVID-19, can speak English, and are willing to follow the study rules. It's not for pregnant or breastfeeding individuals, those with heart disease, bradycardia, vagus nerve surgery in the neck, artery narrowing, undiagnosed pain syndromes or active implants.

Inclusion Criteria

You were diagnosed with dysautonomia after having COVID-19 at least 3 months ago.

Provision of signed and dated informed consent form

Stated willingness to comply with all study procedures and availability for the duration of the study

Exclusion Criteria

You are pregnant or breastfeeding because we don't have enough information about how the study drug might affect you and your baby.

You have been diagnosed with narrowed arteries.

You have unexplained pain that hasn't been diagnosed yet.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either active or sham VNS treatment daily for six weeks

6 weeks

Crossover

Participants in the sham VNS arm crossover to the active VNS arm

6 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Non-invasive vagus nerve stimulation
• Sham Intervention

Trial Overview The study tests non-invasive vagus nerve stimulation against a sham (fake) intervention to see if it helps Long COVID symptoms and improves autonomic nervous system function. It's a placebo-controlled trial with random assignment and participants will experience both interventions.

Participant Groups

Group I: Non-invasive Vagus Nerve Stimulation Experimental Treatment 1 Intervention

Participants in the Non-Invasive Vagus Nerve Stimulation arm will have devices calibrated to a therapeutic setting.

Group II: Sham Vagus Nerve Stimulation Placebo Group 2 Interventions

Participants in the "sham VNS" arm will be asked to use the VNS device daily on a sham setting for six weeks and will be given the opportunity to "crossover" into the active VNS arm once they have completed the sham arm.

Who Is Running the Clinical Trial?

Icahn School of Medicine at Mount Sinai

Lead Sponsor

Trials

933

Recruited

579,000+

Findings from Research

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 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]

Vagus nerve stimulation (VNS) is effective for treating refractory epilepsy and depression, but traditional methods involve surgical implantation, which carries risks such as infection and bradycardia.

New non-invasive VNS systems eliminate the need for surgery, improving safety and tolerability, and allowing patients to administer stimulation on demand, potentially expanding its use in various medical conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. Ben-Menachem, E., Revesz, D., Simon, BJ., et al.[2022]

Vagus nerve stimulation is an effective treatment for drug-resistant epilepsy, but it can have side effects such as cough, voice changes, and, in rare cases, obstructive sleep apnea and arrhythmia.

Guidelines have been developed to help clinicians manage patients with vagus nerve stimulation devices during surgery and critical care, emphasizing the importance of deactivating the device before anesthesia and consulting neurology during critical illness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Management of vagus nerve stimulation therapy in the peri-operative period: Guidelines from the Association of Anaesthetists: Guidelines from the Association of Anaesthetists. Broderick, L., Tuohy, G., Solymos, O., et al.[2023]

Transcutaneous auricular vagus nerve stimulation (taVNS) is generally safe, with a low incidence of mild and transient adverse effects, such as ear pain, headache, and tingling, reported in only 24.86% of the studies analyzed.

In a systematic review of 177 studies involving 6322 subjects, there was no significant difference in the risk of adverse events between taVNS and control groups, indicating that taVNS is a feasible option for clinical intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. Kim, AY., Marduy, A., de Melo, PS., et al.[2023]

References

1. 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]

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

The Use of Non-invasive Vagus Nerve Stimulation to Treat Respiratory Symptoms Associated With COVID-19: A Theoretical Hypothesis and Early Clinical Experience. [2022]

3. 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]

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

A pilot randomized controlled trial of supervised, at-home, self-administered transcutaneous auricular vagus nerve stimulation (taVNS) to manage long COVID symptoms. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Non-invasive Vagus Nerve Stimulation for COVID-19: Results From a Randomized Controlled Trial (SAVIOR I). [2022]

6. England pubmed.ncbi.nlm.nih.gov

Surgically implanted and non-invasive vagus nerve stimulation: a review of efficacy, safety and tolerability. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Management of vagus nerve stimulation therapy in the peri-operative period: Guidelines from the Association of Anaesthetists: Guidelines from the Association of Anaesthetists. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Safety of transcutaneous auricular vagus nerve stimulation (taVNS): a systematic review and meta-analysis. [2023]

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

Auricular Neuromodulation for Mass Vagus Nerve Stimulation: Insights From SOS COVID-19 a Multicentric, Randomized, Controlled, Double-Blind French Pilot Study. [2021]

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

Percutaneous Auricular Vagus Nerve Stimulation Reduces Inflammation in Critical Covid-19 Patients. [2022]