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

Non-invasive Vagal Neurostimulation (nVNS) to Mitigate Traumatic Brain Injury (TBI)-Induced Acute Respiratory Distress and Acute Lung Injury

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).

Study Overview

• Status: Completed
• Conditions: Traumatic Brain Injury; Acute Respiratory Distress Syndrome; Acute Lung Injury; Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
• Intervention / Treatment: Device: nVNS; Other: SOC

Detailed Description

A pilot population of 46 individuals between 18-80 years of age inclusive, will be enrolled, with an in-trial monitoring period of up to 30 days following baseline measurements. Study subjects will remain in-trial until one of the following occurs: a) 30 days without any progression to respiratory distress requiring mechanical ventilation; b) requirement for mechanical ventilation prior to 30 days; or c) death prior to 30 days. In addition to the screening, a total of up to 5 additional in-trial events (depending on the time at discharge from hospitalization) plus one additional clinical site visit at the end of the follow-up period will comprise the study events schedule of this trial.

• Study Type: Interventional
• Enrollment (Actual): 3
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15212
      • AHN Allegheny General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. 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)
2. Woman known to be pregnant, lactating or with a positive (urine or serum test) or indeterminate (serum test) pregnancy test
3. Patient simultaneously taking part in another clinical trial
4. Patient is not expected to survive for 24 hours
5. 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)
6. 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
7. Patient has congestive heart failure
8. Patient has acute left ventricular failure
9. Patient has liver failure (Child-Pugh grade C)
10. Patient is receiving renal dialysis therapy for chronic renal failure
11. Patient is receiving extracorporeal membrane oxygenation, high-frequency oscillatory ventilation (HFOV) or any form of extracorporeal lung support
12. 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
13. Patient has burns to ≥ 15% of their total body surface area

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Receiving Non-invasive vagus neurostimulation; 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; 3x daily treatment of nVNS + SOC; Other: SOC; Standard of care patient management.
Other: Receiving Standard of Care; Patients will be managed according to the institutional best practices and SOC for TBI.	Other: SOC; Standard of care patient management.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-Cause 90-Day Admission to Any Hospital or ED Encounter	A composite endpoint of 90-day presentation to any emergency department and/or 90-day admission to any hospital.	90 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With AEs/SAEs Up to 30 Days From Baseline	30 days from baseline
Number of Participants With Abnormal Physical Examination by Day 30	30 days from baseline
Number of Participants With Abnormal Vital Signs by Day 30	30 days from baseline
Number of Participants With Abnormal Laboratory Results by Day 30	30 days from baseline

Collaborators and Investigators

• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Collaborators: ElectroCore INC; Chuck Noll Foundation
• Investigators: Study Director: Sarah Kimutis, Allegheny Health Network

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2021
• Primary Completion (Actual): March 1, 2025
• Study Completion (Actual): March 1, 2025

Study Registration Dates

• First Submitted: March 12, 2021
• First Submitted That Met QC Criteria: June 15, 2021
• First Posted (Actual): June 23, 2021

Study Record Updates

• Last Update Posted (Actual): May 29, 2026
• Last Update Submitted That Met QC Criteria: May 5, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Non-invasive Vagal Nerve Stimulation
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Respiratory Tract Diseases; Lung Diseases; Respiration Disorders; Craniocerebral Trauma; Trauma, Nervous System; Brain Injuries; Lung Injury; Brain Injuries, Traumatic; Respiratory Distress Syndrome; Acute Lung Injury
• Other Study ID Numbers: nVNS for TBI-ALI/ARDS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No