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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a non-invasive device that stimulates the vagus nerve can help people with Long COVID feel better and improve automatic functions, such as heart rate. Participants will be divided into two groups: one will receive the actual treatment (non-invasive vagus nerve stimulation), while the other will initially receive a placebo but can switch later. Ideal participants are those who have experienced Long COVID symptoms, such as dizziness or abnormal heart rate, for at least three months following their initial COVID-19 infection. As an unphased trial, this study provides a unique opportunity for participants to contribute to pioneering research on innovative treatments for Long COVID.

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.

What prior data suggests that this non-invasive vagus nerve stimulation is safe for treating post-COVID syndrome?

Research has shown that non-invasive vagus nerve stimulation (nVNS) is generally safe for managing Long COVID symptoms. Studies have found that nVNS has few side effects, encouraging those considering trial participation. One study highlighted nVNS's potential as a treatment, emphasizing its safety and effectiveness. Although more research is needed, current evidence suggests that this treatment is well-tolerated and may improve symptoms with minimal risk. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for post-COVID syndrome, which often focus on symptom management through medication and rehabilitation, non-invasive vagus nerve stimulation offers a unique approach by directly targeting the vagus nerve. This method uses electrical impulses to potentially reset and regulate the autonomic nervous system, which can be disrupted after COVID-19. Researchers are excited about this treatment because it provides a non-pharmacological option that could improve symptoms like fatigue and brain fog more effectively and quickly. Additionally, it offers a safe and easy-to-use alternative that patients can administer at home, increasing accessibility and convenience.

What evidence suggests that non-invasive vagus nerve stimulation is effective for Long COVID?

Research has shown that non-invasive vagus nerve stimulation (VNS), a treatment participants in this trial may receive, might help people with Long COVID. One study found that VNS improved symptoms in women with Long COVID. Another review suggested that VNS could alleviate ongoing symptoms by reducing inflammation. Additionally, evidence indicates that VNS can enhance heart function and aid recovery after exercise in individuals with post-COVID conditions. These findings suggest that VNS could be a useful treatment for Long COVID symptoms. ^{1 2 3 4 6}

Who Is on the Research Team?

David Putrino, PT, PhD

Principal Investigator

Icahn School of Medicine at Mount Sinai

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC11097097/

Transcutaneous vagus nerve stimulation improves Long ...

This pilot study provides preliminary evidence supporting the potential of t-VNS as a therapeutic intervention for female Long COVID patients.

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S2772431X24000637

Vagal nerve stimulation for the management of long COVID ...

This review investigates the therapeutic potential of vagal nerve stimulation (VNS) in managing long COVID, a condition marked by persistent symptoms ...

3.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05679505

Vagus Nerve Stimulation for Post-COVID Syndrome

Question 2:Is bilateral auricular transcutaneous vagus nerve stimulation effective in suppressing the symptoms of patients in Post Covid syndrome? A 5-minute ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9028764/

Non-invasive Vagus Nerve Stimulation for COVID-19

Evidence from animal and human studies suggests that vagus nerve stimulation can lead to reduced levels of various biomarkers of inflammation. We conducted a ...

5.

eurasianjpulmonol.com

eurasianjpulmonol.com/storage/upload/pdfs/1733313356-en.pdf

The impact of non-invasive vagus nerve stimulation on ...

Additionally, our results indicated an enhancement in cardiac function and recovery af- ter exercise with VNS in individuals with post-COVID.

6.

amjmed.com

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

Non-Invasive Brain Stimulation for Post-COVID-19 ...

We aim to summarize the current evidence for the effectiveness of non-invasive or minimally invasive brain stimulation techniques in reducing symptoms of post- ...