Neuromodulation With Percutaneous Electrical Nerve Field Stimulation for Adults With COVID-19

NCT ID: NCT04514627

Last Updated: 2024-06-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-13
• Study Completion Date: 2022-03-22

Brief Summary

COVID-19 is a disease caused by the virus, SARS-CoV-2. Patients with this viral infection are at risk for developing pneumonia and acute respiratory distress syndrome (ARDS). Approximately 20% to 30% of hospitalized patients with COVID-19 and pneumonia require intensive care for respiratory support. Clinically, ARDS presents with severe hypoxemia evolving over several days to a week in combination with bilateral pulmonary infiltrates on chest X-ray. Widespread alveolar epithelial cell and pulmonary capillary endothelial injury can lead to severe impairment in gas exchange. In one report of 1,099 patients hospitalized with COVID-19, ARDS occurred in 15.6% of patients with severe pneumonia. In a smaller case series of 138 hospitalized patients, ARDS occurred in 19.6% of patients and in 61.1% of patients admitted to an intensive care unit (ICU).

To date, no effective treatment has been established to treat COVID-19 or to prevent progression of ARDS. It is thought that a heightened immune response with an unbalanced release of inflammatory mediators in the airway is a major cause of morbidity and mortality associated with the disease. It is therefore reasonable to postulate that improved outcomes may be obtained in patients with a balanced immune response with adequate viral control and appropriate counter-regulatory immune responses whereas a poor outcome may be expected in patients with inadequate viral control or a heightened immune response or what is referred to as a "cytokine storm". Thus, modulating the pulmonary immune response without suppressing the immune system would be a viable strategy for patients with COVID-19. The current literature supports the role of neuromodulation, particularly vagal nerve stimulation (VNS), in modulating the immune response. Modulating the pro-inflammatory pathway through VNS has been demonstrated to decrease inflammatory mediators and improve outcomes in several animal models and in humans.

Percutaneous electrical nerve field stimulation (PENFS) provides a novel, non-invasive method of VNS through a non-implantable device applied to the external ear. Already, the FDA has cleared this technology for reducing symptoms of opioid withdrawal in patients with opioid use disorder. Symptoms of opioid withdrawal can be decreased by approximately 90% after 1 hour of stimulation. Similarly, the IB-Stim device has been shown to improve symptom in children with abdominal-pain-related functional GI disorders and recently received market approval by the FDA for that indication. Unpublished studies have demonstrated marked decrease in inflammation with PENFS compared to sham stimulation in a model of TNBS colitis. While the efficacy of PENFS in modulating the progression of pulmonary disease in patients with COVID-19 is unknown, several proposed mechanisms for regulation of the immune response through VNS have already been demonstrated. We propose to perform an open label, randomized study to evaluate the efficacy of PENFS for the treatment of respiratory symptoms in patients with COVID-19.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active percutaneous neurostimulation

Subject randomized to 5 days of active vs sham neurostimulation therapy during hospitalization.

Group Type: ACTIVE_COMPARATOR

Auricular percutaneous neurostimulation

Intervention Type: DEVICE

The BRIDGE/PENFS device manufactured by Key Electronics, consists of a battery activated generator and wire harness that connects to the generator. Four leads are also attached to the generator, each with a sterile 2 mm, titanium needle. The BRIDGE device settings are standardized and deliver 3.2 volts with alternating frequencies (1 ms pulses of 1 Hz and 10 Hz) every 2 s. This stimulation targets central pain pathways through branches of cranial nerves V, VII, IX, and X, which innervate the external ear. The PENFS device generator has a battery life of 5 days and delivers almost continuous stimulations throughout the 120 hours.

Sham percutaneous neurostimulation

Each subject randomized to 5 days of active vs sham neurostimulation therapy during hospitalization.

Group Type: SHAM_COMPARATOR

Auricular percutaneous neurostimulation

Intervention Type: DEVICE

The BRIDGE/PENFS device manufactured by Key Electronics, consists of a battery activated generator and wire harness that connects to the generator. Four leads are also attached to the generator, each with a sterile 2 mm, titanium needle. The BRIDGE device settings are standardized and deliver 3.2 volts with alternating frequencies (1 ms pulses of 1 Hz and 10 Hz) every 2 s. This stimulation targets central pain pathways through branches of cranial nerves V, VII, IX, and X, which innervate the external ear. The PENFS device generator has a battery life of 5 days and delivers almost continuous stimulations throughout the 120 hours.

Interventions

Auricular percutaneous neurostimulation

The BRIDGE/PENFS device manufactured by Key Electronics, consists of a battery activated generator and wire harness that connects to the generator. Four leads are also attached to the generator, each with a sterile 2 mm, titanium needle. The BRIDGE device settings are standardized and deliver 3.2 volts with alternating frequencies (1 ms pulses of 1 Hz and 10 Hz) every 2 s. This stimulation targets central pain pathways through branches of cranial nerves V, VII, IX, and X, which innervate the external ear. The PENFS device generator has a battery life of 5 days and delivers almost continuous stimulations throughout the 120 hours.

Intervention Type: DEVICE

Other Intervention Names

Neuro-Stim System (NSS)-2 BRIDGE

Eligibility Criteria

Inclusion Criteria

• Age ≥18 years at time of signing Informed Consent Form
• Hospitalized with COVID-19 pneumonia confirmed per WHO criteria (including a positive PCR of any specimen, e.g., respiratory, blood, urine, stool, other bodily fluid) and per the investigator, the respiratory compromise is most likely due to COVID-19
• Patient complaint of dyspnea at the time of presentation to ED or hospital
• Patient on room air or oxygen supplementation of no greater than 4 liters at rest to maintaining pulse oximetry of 92% or greater. This can include oxygen supplementation by any modality (BIPAP, CPAP, HFNC, NRB, NC), with the exception of mechanical ventilation or ECLS.
• Signed Informed Consent Form by any patient capable of giving consent, or, when the patient is not capable of giving consent, by his or her legal/authorized representative
• Ability to comply with the study protocol in the investigator's judgment.

Exclusion Criteria

• Patients who cannot provide informed consent
• History of surgery involving CN V, VII, IX, or X.
• Patient on chronic renal dialysis
• Patients with history of solid organ transplant
• Patients with underlying seizures disorder
• Patients with a cardiac pacemaker
• Patients with any implanted electrical device
• Patients with dermatologic conditions affecting the ear, face, or neck region (i.e. psoriasis), or with cuts or abrasions to the external ear that would interfere with needle placement
• Patients with hemophilia or other bleeding disorders
• Patients who are pregnant or breastfeeding
• Patients with active TB infection
• Patient already on mechanical ventilation or ECLS
• Suspected active bacterial, fungal, viral, or other infection (besides COVID-19)
• In the opinion of the investigator, progression to mechanical ventilation, ECLS or death is imminent and inevitable within the next 24 hours, irrespective of the provision of treatments
• Participating in other drug clinical trials
• ALT or AST > 5 x ULN detected within 24 hours at screening or at baseline (according to local laboratory reference ranges)
• ANC < 500/µL at screening and baseline (according to local laboratory reference ranges)
• Platelet count < 50,000/µL at screening and baseline (according to local laboratory reference ranges)
• Any serious medical condition or abnormality of clinical laboratory tests that, in the investigator's judgment, precludes the patient's safe participation in and completion of the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Olive View-UCLA Education & Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Nader Kamangar, M.D.

Role: PRINCIPAL_INVESTIGATOR

Olive View-UCLA Education & Research Institute

Locations

Olive View-UCLA Medical Center

Sylmar, California, United States

Countries

United States

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Other Identifiers

1600899

Identifier Type: -

Identifier Source: org_study_id