Non-invasive Vagal Neurostimulation (nVNS) for Traumatic Brain Injury (TBI)-Induced Acute Respiratory Distress

NCT04935697 | Completed DMC FDA Device

• 1 other identifier: nVNS for TBI-ALI/ARDS
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, randomized, two-arm, controlled 30-day investigational pilot trial using the gammaCore Sapphire S non-invasive vagus nerve stimulation (nVNS) device + standard of care (SOC) in newly-hospitalized patients with mild-to-moderate traumatic brain injury (TBI) to prevent the progression towards immunokine storms, systemic inflammatory response syndrome (SIRS), severe respiratory distress, and requirement for invasive mechanical ventilation, and death, when compared to SOC alone (the control arm).

Conditions

Acute Respiratory Distress Syndrome; Acute Lung Injury; Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS); Traumatic Brain Injury

Keywords

Non-invasive Vagal Nerve Stimulation

Outcome Measures

Primary Outcomes (2)

• Days free of invasive mechanical ventilation

  Days free of invasive mechanical ventilation within 30 days from baseline among TBI survivors.

  30 days from baseline

• Days free of death

  Days free of death within 30 days from baseline

  30 days from baseline

Secondary Outcomes (15)

• Adverse Events/Serious Adverse Events (AEs/SAEs)

  Day 30 from baseline, Day 60, Day 90

• Incidence of abnormal Physical examinations

  Day 30 from baseline or last day in hospital, Day 60, Day 90

• Incidence of abnormal vital signs

  Day 30 from baseline or last day in hospital, Day 60, Day 90

• Incidence of abnormal laboratory results

  Day 30 from baseline or last day in hospital, Day 60, Day 90

• All-cause mortality

  Day 30 from baseline, Day 60, Day 90

Study Arms (2)

Receiving Non-invasive vagus neurostimulation

EXPERIMENTAL

nVNS treatment will be applied three times daily. One treatment is defined as 2 consecutive stimulations: one, 2-minute stimulation on the side of the neck followed by a second, 2-minute stimulation on the same side of the neck. The treatment will be done 3 times per day (morning, mid-day and 1 hour before bed at night), every day, until patient is discharged from the hospital or requires mechanical ventilation. Patient will record the time they administered these treatments. If the patient is unable to do this, a research staff member who has been trained on the device can assist. Will also receive SOC for TBI.

Device: nVNS; Other: SOC

Receiving Standard of Care

OTHER

Patients will be managed according to the institutional best practices and SOC for TBI.

Other: SOC

Interventions

nVNS DEVICE

3x daily treatment of nVNS + SOC

Receiving Non-invasive vagus neurostimulation

SOC OTHER

Standard of care patient management.

Receiving Non-invasive vagus neurostimulation; Receiving Standard of Care

Eligibility Criteria

• Age: 12 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient is between 12-80 years, inclusive
• Patient has been admitted to the hospital for mild-to-moderate TBI that is restricted to the head and/or neck region.
• Patient is not on invasive mechanical ventilation
• Patient has a mild-to-moderate TBI based on a non-resuscitated or post-resuscitated Glasgow Coma Scale (GCS) sum score of =\>12
• Patient has a Lung Injury Prediction Score (LIPS) of =\>2
• Administration of the first nVNS treatment must be planned to take place within 24 h of intake
• A signed, written informed consent form from the patient or legally authorized representative

You may not qualify if:

• Patient has a diagnosis of moderate or greater grade of respiratory distress/ARDS according to the Berlin definition of ARDS: Partial pressure of oxygen (PaO2) /Fraction of Inspired Oxygen (FiO2) \> 100 mmHg (\>13.3 kPa) to ≤ 200 mmHg (≤ 26.6 kPa) with positive end-expiratory pressure (PEEP) ≥ 5 cmH2O)
• Woman known to be pregnant, lactating or with a positive (urine or serum test) or indeterminate (serum test) pregnancy test
• Patient simultaneously taking part in another clinical trial
• Patient is not expected to survive for 24 hours
• Patient has an underlying clinical condition where, in the opinion of the study physicians and the institutional health provider physician, it would be extremely unlikely that the patient would not progress to invasive mechanical ventilation within 48 hours or any other condition that might require immediate invasive mechanical ventilation (e.g. motor neuron disease, Duchenne muscular dystrophy, or rapidly-progressive interstitial pulmonary fibrosis)
• Patient has severe chronic obstructive pulmonary disease (COPD) requiring long-term home oxygen therapy or mechanical ventilation (non-invasive ventilation or via tracheotomy) except for continuous positive airway pressure (CPAP) or bi-level positive airway pressure (BIPAP) used solely for sleep-disorder breathing
• Patient has congestive heart failure
• Patient has acute left ventricular failure
• Patient has liver failure (Child-Pugh grade C)
• Patient is receiving renal dialysis therapy for chronic renal failure
• Patient is receiving extracorporeal membrane oxygenation, high-frequency oscillatory ventilation (HFOV) or any form of extracorporeal lung support
• Patient has had any form of mechanical ventilation (invasive or non-invasive, excluding CPAP alone) for longer than 48 h prior to the diagnosis of mild-to-moderate respiratory distress/ARDS
• Patient has burns to ≥ 15% of their total body surface area

Sponsors & Collaborators

• ElectroCore INC: collaborator
• Chuck Noll Foundation: collaborator
• Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute): lead

Study Sites (1)

AHN Allegheny General Hospital

Pittsburgh, Pennsylvania, 15212, United States

Location

MeSH Terms

Conditions

Respiratory Distress Syndrome; Acute Lung Injury; Brain Injuries, Traumatic

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Lung Injury; Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Study Officials

• Sarah Kimutis

  Allegheny Health Network

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 12, 2021
• First Posted: June 23, 2021
• Study Start: August 4, 2021
• Primary Completion: March 1, 2025
• Study Completion: March 1, 2025
• Last Updated: February 9, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)