Severe Acute Respiratory Syndrome Coronavirus 2NCT04379037
Vagus Nerve Stimulation ARDS Prevention Trial for COVID-19 Hospitalized Patients
A study testing Transcutaneous Auricular Vagus Nerve Stimulation in people with Severe Acute Respiratory Syndrome Coronavirus 2, run by Nemechek Technologies at 1 site in Argentina.
Trial summary
This trial is designed to determine if the inflammation modulating effect of vagus nerve stimulation can improve pulmonary function and limit progression to ARDS in hospitalized COVID-19 hospitalized patients. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Acute Respiratory Syndrome Coronavirus 2
- What is being tested?
- Transcutaneous Auricular Vagus Nerve Stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteArgentina
- Study dates
- 27 Jun 2020to 1 Nov 2020
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who are 18 years of age
- Tested positive or suspected/presumed positive for COVID-19 infection
- Patients requiring hospital admission moderate to severe pneumonia and pneumopathy
- Patients showing fever and respiratory symptoms with radiological findings of pneumonia
- Respiratory distress (≧30 breaths/ min) or Oxygen saturation ≤93% at rest in ambient air; or oxygen saturation ≤97 % with O2 > 5L/min
- Patient is able to provide signed and witnessed Informed Consent
Who cannot join
- Already enrolled in a trial for COVID-19 therapy
- Potentially life threatening heart rhythm
- Pregnancy or potential pregnancy
- Current implantation of an electrical and/or neurostimulator device, including but not limited to a cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant
- History of aneurysm, intracranial hemorrhage, brain tumors, or significant head trauma
- Belongs to a vulnerable population or has any condition such that his or her ability to provide informed consent, comply with the follow-up requirements, or provide self-assessments is compromised (e.g. homeless, developmentally disabled and prisoner)
Trial locations and contacts
1 site in 1 country.
Argentina1 site
Hospital Zonal Virgen del Carmen de Zárate
Zárate, Buenos Aires, B2800DDF
About this study
This trial is designed to determine if the inflammation modulating effect of vagus nerve stimulation can improve pulmonary function and limit progression to ARDS in hospitalized COVID-19 hospitalized patients.
Read the detailed description
Patients hospitalized with COVID-19 predominantly die of organ failure due to a surge of pro-inflammatory cytokines triggering the need for mechanical ventilation, often due to acute respiratory distress syndrome (ARDS). Known as a cytokine storm, the surge in cytokines is similar to the excessive inflammatory reaction associated with septic shock.
Anti-viral agents will most likely be required to reduce the molecular viral burden in COVID-19 patients, but an additional approach to control the damaging cytokine release is required to alter the course of disease in hospitalized patients and improve chances of survival. Immunosuppressant drugs may reduce inflammation and the tissue damaging cytokines, but they could also be detrimental by inhibiting natural anti-viral immune responses (i.e., suppression of interferons), thereby delaying viral clearance and increasing the risk of secondary infections and death.
The reason for the severity of the disease course in some individuals may lie in the regulation of the immune system by the vagus nerve. The vagus nerve is involved in an inflammation controlling reflex similar to the blood pressure regulating baroreflex. The vagus inflammatory reflex is triggered when the afferent vagus nerve senses inflammatory products through peripheral receptors.
Vagus nerve activity is relayed through the central nervous system to the efferent vagus nerve. This pathway involves the splenic nerve, which when activated releases norepinephrine and results in suppression of pro-inflammatory cytokine production by macrophages and alleviates inflammation in many pathological settings (e.g., endotoxemia, peritonitis, or acute kidney injury).
Electrical stimulation of the vagus nerve using VNS can improve the body's natural ability to regulate the inflammatory response and may be potent enough to suppress pro-inflammatory cytokines and prevent death from COVID-19, especially if used early enough in the course of hospitalization.
In rat models of sepsis, VNS attenuates the release of pro-inflammatory cytokines, prevents hypotension, modulates coagulation, and prevents fibrinolysis activation, decreasing organ dysfunction, and improving survival. Human studies also demonstrate that VNS suppresses the production of pro-inflammatory cytokines and improves clinical symptoms in rheumatoid arthritis, intractable epilepsy, atrial fibrillation, and Crohn's Disease.
This suggests that VNS may be effective in treating disorders characterized by cytokine dysregulation and that it has the potential to prevent hospitalized patients with COVID-19 from progressing to respiratory failure and death.
- Being tested
- Transcutaneous Auricular Vagus Nerve Stimulation
- Keywords
- vagus nerve stimulation, COVID-19, Acute Respiratory Distress Syndrome
- Medical subject headings
- COVID-19, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous Auricular Vagus Nerve StimulationDevice
Transcutaneous vagus nerve stimulation involves stimulating the auricular branch of the vagus nerve with a imperceptible electrical current within the concha of the ear.
| Study group | Role | What they receive |
|---|---|---|
| Intervention Arm | Experimental | Adults over 18 years of age hospitalized because of COVID-19 infection will be treated with transcutaneous auricular vagus nerve stimulation (taVNS). Receives: Device: Transcutaneous Auricular Vagus Nerve Stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival without need of mechanical ventilation
Survival
Measured: Day 14 since symptom onset
Cumulative incidence of successful tracheal extubation at day 14 since symptom onset.
Successful tracheal extubation
Measured: Day 14 since symptom onset
Secondary outcomes (2)
Survival at day 14 of hospitalization
Survival
Measured: Day 14
Duration of hospitalization
Duration of hospitalization
Measured: Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 May 2020
- Study start27 Jun 2020
- Primary completion1 Sep 2020
- Study completion1 Nov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Severe Acute Respiratory Syndrome Coronavirus 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The objective of this study is to determine the therapeutic effect of transcutaneous vagus nerve stimulation in patients with moderate, severe or critical pneumonia associated with Coronavirus Disease 2019 (COVID-19).
- Masking
- None (open label)
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nemechek Technologies
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04379037
- Sponsor's protocol ID
- NCM-001
- Status last verified
- Jun 2021
- First submitted
- 5 May 2020
- Last updated
- 4 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.
PubMed 32192578Kaniusas E, Kampusch S, Tittgemeyer M, Panetsos F, Gines RF, Papa M, Kiss A, Podesser B, Cassara AM, Tanghe E, Samoudi AM, Tarnaud T, Joseph W, Marozas V, Lukosevicius A, Istuk N, Sarolic A, Lechner S, Klonowski W, Varoneckas G, Szeles JC. Current Directions in the Auricular Vagus Nerve Stimulation I - A Physiological Perspective. Front Neurosci. 2019 Aug 9;13:854. doi: 10.3389/fnins.2019.00854. eCollection 2019.
PubMed 31447643Tanaka S, Hammond B, Rosin DL, Okusa MD. Neuroimmunomodulation of tissue injury and disease: an expanding view of the inflammatory reflex pathway. Bioelectron Med. 2019 Aug 13;5:13. doi: 10.1186/s42234-019-0029-8. eCollection 2019.
PubMed 32232102Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.
PubMed 32217835
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vagus Nerve Stimulation ARDS Prevention Trial for COVID-19 Hospitalized Patients
- ClinicalTrials.gov ID
- NCT04379037
- Acronym / sponsor ID
- NCM-001
- Keywords
- vagus nerve stimulation, COVID-19, Acute Respiratory Distress Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Nemechek TechnologiesIndustry (pharma, biotech, devices)
- Study start
- 27 Jun 2020 (actual)
- Primary completion
- 1 Sep 2020 (actual)
- Study completion
- 1 Nov 2020 (actual)
- First posted
- 7 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This trial is designed to determine if the inflammation modulating effect of vagus nerve stimulation can improve pulmonary function and limit progression to ARDS in hospitalized COVID-19 hospitalized patients.
Detailed description
Patients hospitalized with COVID-19 predominantly die of organ failure due to a surge of pro-inflammatory cytokines triggering the need for mechanical ventilation, often due to acute respiratory distress syndrome (ARDS). Known as a cytokine storm, the surge in cytokines is similar to the excessive inflammatory reaction associated with septic shock.
Anti-viral agents will most likely be required to reduce the molecular viral burden in COVID-19 patients, but an additional approach to control the damaging cytokine release is required to alter the course of disease in hospitalized patients and improve chances of survival. Immunosuppressant drugs may reduce inflammation and the tissue damaging cytokines, but they could also be detrimental by inhibiting natural anti-viral immune responses (i.e., suppression of interferons), thereby delaying viral clearance and increasing the risk of secondary infections and death.
The reason for the severity of the disease course in some individuals may lie in the regulation of the immune system by the vagus nerve. The vagus nerve is involved in an inflammation controlling reflex similar to the blood pressure regulating baroreflex. The vagus inflammatory reflex is triggered when the afferent vagus nerve senses inflammatory products through peripheral receptors.
Vagus nerve activity is relayed through the central nervous system to the efferent vagus nerve. This pathway involves the splenic nerve, which when activated releases norepinephrine and results in suppression of pro-inflammatory cytokine production by macrophages and alleviates inflammation in many pathological settings (e.g., endotoxemia, peritonitis, or acute kidney injury).
Electrical stimulation of the vagus nerve using VNS can improve the body's natural ability to regulate the inflammatory response and may be potent enough to suppress pro-inflammatory cytokines and prevent death from COVID-19, especially if used early enough in the course of hospitalization.
In rat models of sepsis, VNS attenuates the release of pro-inflammatory cytokines, prevents hypotension, modulates coagulation, and prevents fibrinolysis activation, decreasing organ dysfunction, and improving survival. Human studies also demonstrate that VNS suppresses the production of pro-inflammatory cytokines and improves clinical symptoms in rheumatoid arthritis, intractable epilepsy, atrial fibrillation, and Crohn's Disease.
This suggests that VNS may be effective in treating disorders characterized by cytokine dysregulation and that it has the potential to prevent hospitalized patients with COVID-19 from progressing to respiratory failure and death.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The objective of this study is to determine the therapeutic effect of transcutaneous vagus nerve stimulation in patients with moderate, severe or critical pneumonia associated with Coronavirus Disease 2019 (COVID-19).
| Arm | Type | Receives |
|---|---|---|
| Intervention Arm | Experimental | Device: Transcutaneous Auricular Vagus Nerve StimulationAdults over 18 years of age hospitalized because of COVID-19 infection will be treated with transcutaneous auricular vagus nerve stimulation (taVNS). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients who are 18 years of age
- Tested positive or suspected/presumed positive for COVID-19 infection
- Patients requiring hospital admission moderate to severe pneumonia and pneumopathy
- Patients showing fever and respiratory symptoms with radiological findings of pneumonia
- Respiratory distress (≧30 breaths/ min) or Oxygen saturation ≤93% at rest in ambient air; or oxygen saturation ≤97 % with O2 > 5L/min
Key exclusion criteria (6 listed)
- Already enrolled in a trial for COVID-19 therapy
- Potentially life threatening heart rhythm
- Pregnancy or potential pregnancy
- Current implantation of an electrical and/or neurostimulator device, including but not limited to a cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant
- History of aneurysm, intracranial hemorrhage, brain tumors, or significant head trauma
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous Auricular Vagus Nerve StimulationTranscutaneous vagus nerve stimulation involves stimulating the auricular branch of the vagus nerve with a imperceptible electrical current within the concha of the ear. | Device | Intervention Arm |
Primary outcome
Survival without need of mechanical ventilation
Time frame: Day 14 since symptom onset
Survival
Cumulative incidence of successful tracheal extubation at day 14 since symptom onset.
Time frame: Day 14 since symptom onset
Successful tracheal extubation
2 secondary outcomes
Survival at day 14 of hospitalization
Time frame: Day 14
Duration of hospitalization
Time frame: Day 28
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2021.
- Background: PubMed 32192578Mehta P, McAuley DF, Brown M, Sanchez E, Tattersall RS, Manson JJ; HLH Across Speciality Collaboration, UK. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet. 2020 Mar 28;395(10229):1033-1034. doi: 10.1016/S0140-6736(20)30628-0. Epub 2020 Mar 16. No abstract available.
- Background: PubMed 31447643Kaniusas E, Kampusch S, Tittgemeyer M, Panetsos F, Gines RF, Papa M, Kiss A, Podesser B, Cassara AM, Tanghe E, Samoudi AM, Tarnaud T, Joseph W, Marozas V, Lukosevicius A, Istuk N, Sarolic A, Lechner S, Klonowski W, Varoneckas G, Szeles JC. Current Directions in the Auricular Vagus Nerve Stimulation I - A Physiological Perspective. Front Neurosci. 2019 Aug 9;13:854. doi: 10.3389/fnins.2019.00854. eCollection 2019.
- Background: PubMed 32232102Tanaka S, Hammond B, Rosin DL, Okusa MD. Neuroimmunomodulation of tissue injury and disease: an expanding view of the inflammatory reflex pathway. Bioelectron Med. 2019 Aug 13;5:13. doi: 10.1186/s42234-019-0029-8. eCollection 2019.
- Background: PubMed 32217835Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, Wang T, Zhang X, Chen H, Yu H, Zhang X, Zhang M, Wu S, Song J, Chen T, Han M, Li S, Luo X, Zhao J, Ning Q. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020 May 1;130(5):2620-2629. doi: 10.1172/JCI137244.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous Auricular Vagus Nerve Stimulation in people with Severe Acute Respiratory Syndrome Coronavirus 2, run by Nemechek Technologies at 1 site in Argentina.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Argentina. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival without need of mechanical ventilation (time frame: Day 14 since symptom onset). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04379037, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2021.