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?

This trial tests a treatment called transcutaneous vagus nerve stimulation (tVNS) to assist people with long COVID who experience symptoms like chronic fatigue. The goal is to determine which of two methods of using the device best improves quality of life over six weeks. One group will control the device themselves, while the other group will use a device that adjusts the stimulation automatically. The trial seeks participants who have had COVID-19 and now experience severe fatigue, brain fog, or pain affecting their daily life. Participants will use the device daily for 35 minutes. As an unphased trial, this study provides a unique opportunity to contribute to understanding new ways to improve life for those with 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.

What prior data suggests that this device is safe for post-COVID syndrome patients?

Research has shown that transcutaneous vagus nerve stimulation (tVNS) is generally safe and well-tolerated for individuals with long COVID symptoms. Studies have found that tVNS can improve the health of some patients with post-COVID conditions. Although no major safety issues have been reported, individual experiences may vary. Overall, tVNS is considered a safe option for managing ongoing symptoms related to long COVID. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using a transcutaneous vagus nerve stimulator for post-COVID syndrome because it offers a non-invasive way to potentially alleviate symptoms. Unlike traditional treatments that typically involve medications like pain relievers, anti-inflammatory drugs, or therapies focused on specific symptoms, this device directly stimulates the vagus nerve through the skin, which might help regulate the body's recovery processes more holistically. With one approach being patient-controlled and the other device-controlled, the treatment allows for a personalized experience, potentially offering relief without the usual medication side effects. This innovative method could provide a new avenue for symptom management in those struggling with long-term effects of COVID-19.

What evidence suggests that the Transcutaneous Vagus Nerve Stimulator is effective for Post-COVID Syndrome?

Research has shown that transcutaneous vagus nerve stimulation (tVNS) may help with post-COVID syndrome. In this trial, participants will join one of two treatment arms: one with patient-controlled stimulation and another with device-controlled stimulation. A previous study found that tVNS reduced symptoms like fatigue and depression in people with long COVID. This treatment stimulates the vagus nerve, potentially helping to control the body's response to stress and inflammation. Early results indicate that people using tVNS experienced improvement and a better quality of life. Although the data remains in the early stages, these findings offer promise for those with long-term COVID symptoms. ^{1 2 3 5 6}

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 experience significant fatigue, pain, brain fog, or post-exertional malaise.

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

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]

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]

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 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) 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]

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 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]

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]

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]

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Study Details | NCT06585254 | tVNS in Long COVID-19

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 ...

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TVNS in Long COVID-19 | Mount Sinai - New York

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- ...