Vagus Nerve Stimulation ARDS Prevention Trial for COVID-19 Hospitalized Patients
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|ClinicalTrials.gov Identifier: NCT04379037|
Recruitment Status : Recruiting
First Posted : May 7, 2020
Last Update Posted : July 7, 2020
|Condition or disease||Intervention/treatment||Phase|
|Severe Acute Respiratory Syndrome Coronavirus 2||Device: Transcutaneous Auricular Vagus Nerve Stimulation||Not Applicable|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Intervention 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)|
|Official Title:||Vagus Nerve Stimulation ARDS Prevention Trial for COVID-19 Hospitalized Patients|
|Actual Study Start Date :||June 27, 2020|
|Estimated Primary Completion Date :||September 1, 2020|
|Estimated Study Completion Date :||November 1, 2020|
Experimental: Intervention Arm
Adults over 18 years of age hospitalized because of COVID-19 infection will be treated with transcutaneous auricular vagus nerve stimulation (taVNS).
Device: Transcutaneous Auricular Vagus Nerve Stimulation
Transcutaneous vagus nerve stimulation involves stimulating the auricular branch of the vagus nerve with a imperceptible electrical current within the concha of the ear.
- Survival without need of mechanical ventilation [ Time Frame: Day 14 since symptom onset ]Survival
- WHO progression scale ≤ 5 at day 4 since admission. [ Time Frame: Score on day 4 since admission ]WHO Progression Scale
- Cumulative incidence of successful tracheal extubation at day 14 since symptom onset. [ Time Frame: Day 14 since symptom onset ]Successful tracheal extubation
- WHO progression scale ≤ 7 at day 4 since admission. [ Time Frame: Score on day 7 since admission ]WHO Progression Scale
- Survival at day 14 of hospitalization [ Time Frame: Day 14 ]Survival
- Duration of hospitalization [ Time Frame: Day 28 ]Duration of hospitalization
- Time to hospital discharge [ Time Frame: Day 28 ]Time to hospital discharge
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04379037
|Contact: Patrick M Nemechek, D.O.||firstname.lastname@example.org|
|Contact: Jean R Nemechek, JDemail@example.com|
|Hospital Zonal Virgen del Carmen de Zárate||Recruiting|
|Zárate, Buenos Aires, Argentina, B2800DDF|