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

• ClinicalTrials.gov Identifier: NCT04935697
• Recruitment Status: Recruiting
• First Posted: June 23, 2021
• Last Update Posted: March 3, 2023
• Sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Collaborators: ElectroCore INC; Chuck Noll Foundation
• Information provided by (Responsible Party): Boyle Cheng, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Study Description

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).

Condition or disease	Intervention/treatment	Phase
Acute Respiratory Distress Syndrome; Acute Lung Injury; Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS); Traumatic Brain Injury	Device: nVNS; Other: SOC	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 46 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Non-invasive Vagal Neurostimulation (nVNS) to Mitigate Traumatic Brain Injury (TBI)-Induced Acute Respiratory Distress and Acute Lung Injury
• Actual Study Start Date: August 4, 2021
• Estimated Primary Completion Date: December 2025
• Estimated Study Completion Date: December 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: nVNS; 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.
SOC only; Patients will be managed according to the institutional best practices and SOC for TBI.	Other: SOC; Standard of care patient management.

Outcome Measures

Primary Outcome Measures :

1. Days free of invasive mechanical ventilation [ Time Frame: 30 days from baseline ]
   Days free of invasive mechanical ventilation within 30 days from baseline among TBI survivors.
2. Days free of death [ Time Frame: 30 days from baseline ]
   Days free of death within 30 days from baseline

Secondary Outcome Measures :

1. Adverse Events/Serious Adverse Events (AEs/SAEs) [ Time Frame: Day 30 from baseline, Day 60, Day 90 ]
   Incidence, rate and severity of AEs/SAEs
2. Incidence of abnormal Physical examinations [ Time Frame: Day 30 from baseline or last day in hospital, Day 60, Day 90 ]
   Physical examination results
3. Incidence of abnormal vital signs [ Time Frame: Day 30 from baseline or last day in hospital, Day 60, Day 90 ]
   vital sign results
4. Incidence of abnormal laboratory results [ Time Frame: Day 30 from baseline or last day in hospital, Day 60, Day 90 ]
   laboratory results
5. All-cause mortality [ Time Frame: Day 30 from baseline, Day 60, Day 90 ]
   All-cause mortality
6. Days free of organ failure [ Time Frame: Day 30 from baseline or last day in study, Day 60, Day 90 ]
   assessed using the Sequential Organ Failure Assessment (SOFA) score (numerically quantifies (0-4) the number and severity of failed organs) with higher number being worse
7. Days free of renal support [ Time Frame: Day 30 from baseline or last day in study ]
8. Days free of vasoactive support [ Time Frame: Day 30 from baseline or last day in study ]
9. Number of ICU-free days [ Time Frame: Day 30 from baseline ]
   assessed at Day 30 or on the last day in the ICU if the patient leaves the ICU before Day 30
10. Days free of invasive mechanical ventilation [ Time Frame: Day 30 from baseline of last day in study ]
11. Length of hospital stay [ Time Frame: Study Completion (up to 95 days from baseline) ]
    Number of days in hospital
12. Forced Expiratory Volume (FEV1) [ Time Frame: Day 30 from baseline, Day 60 from baseline, Day 90 from baseline ]
13. Neurological functioning [ Time Frame: Day 30 from baseline, Day 60 from baseline, Day 90 from baseline ]
    6 minute walk test
14. PROMIS CAT score (Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive testing (CAT)) [ Time Frame: Day 30 from baseline, Day 60 from baseline, Day 90 from baseline ]
    0 to 100, with 0 being the lowest physical function and most disabled and 100 having the highest functioning
15. Post concussion symptom scale (PCSS) [ Time Frame: Day 30 from baseline, Day 60 from baseline, Day 90 from baseline ]
    27 perceived symptoms, patient reports their current experience of symptoms, on a scale from 0 to 6, with 0 being "none/not experiencing particular symptom" to 6 being experiencing "severe" symptom; total point value of scale is from 0 to 162

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

1. Patient is between 18-80 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

Contacts and Locations

Contacts

Contact: Boyle Cheng, PhD; 412-359-4020; Boyle.Cheng@ahn.org

Contact: Tibetha Santucci, RN; 412-359-8721; tibetha.santucci@ahn.org

Locations

United States, Pennsylvania

AHN Allegheny General Hospital; Recruiting

Pittsburgh, Pennsylvania, United States, 15212

Contact: Boyle Cheng, PhD 412-359-4020 boyle.cheng@ahn.org

Contact: Tibetha Santucci, RN 412-359-8721 tibetha.santucci@ahn.org

Principal Investigator: Boyle Cheng, PhD

Sub-Investigator: Obiad Ashraf, MD

Sub-Investigator: Tariq Cheema, MD

Sub-Investigator: Justin Davanzo, MD

Sub-Investigator: Nick Giannoukakis, PhD

Sub-Investigator: Edward Snell, MD

Sub-Investigator: Jennifer Chen, MD

Sub-Investigator: Allan Philp, MD

Sub-Investigator: William Rieck, DO

Sub-Investigator: Alexander Yu, MD

Sponsors and Collaborators

Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

ElectroCore INC

Chuck Noll Foundation

Investigators

• Principal Investigator: Boyle Cheng, PhD; Allegheny Health Network

More Information

• Responsible Party: Boyle Cheng, Principal Investigator, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• ClinicalTrials.gov Identifier: NCT04935697
• Other Study ID Numbers: nVNS for TBI-ALI/ARDS
• First Posted: June 23, 2021
• Last Update Posted: March 3, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by Boyle Cheng, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute):

Non-invasive Vagal Nerve Stimulation

Additional relevant MeSH terms:

Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury; Lung Injury; Brain Injuries; Brain Injuries, Traumatic; Syndrome; Wounds and Injuries; Disease; Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Infant, Premature, Diseases; Infant, Newborn, Diseases; Thoracic Injuries