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

Traumatic Brain Injury Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04935697
• Other study ID #: nVNS for TBI-ALI/ARDS
• Status: Recruiting
• Phase: N/A
• Start date: August 4, 2021
• Est. completion date: December 2025

Study information

• Verified date: March 2023
• Source: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
• Contact: Boyle Cheng, PhD
• Phone: 412-359-4020
• Email: Boyle.Cheng[@]ahn.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 46
• Est. completion date: December 2025
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Acute Lung Injury
• Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
• Acute Respiratory Distress Syndrome
• Brain Injuries
• Brain Injuries, Traumatic
• Lung Injury
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Newborn
• Syndrome
• Traumatic Brain Injury
• Wounds and Injuries

Intervention

Device:
• nVNS
3x daily treatment of nVNS + SOC

Other:
• SOC
Standard of care patient management.

Locations

Country	Name	City	State
United States	AHN Allegheny General Hospital	Pittsburgh	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)	Chuck Noll Foundation, ElectroCore INC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Days free of invasive mechanical ventilation	Days free of invasive mechanical ventilation within 30 days from baseline among TBI survivors.	30 days from baseline
Primary	Days free of death	Days free of death within 30 days from baseline	30 days from baseline
Secondary	Adverse Events/Serious Adverse Events (AEs/SAEs)	Incidence, rate and severity of AEs/SAEs	Day 30 from baseline, Day 60, Day 90
Secondary	Incidence of abnormal Physical examinations	Physical examination results	Day 30 from baseline or last day in hospital, Day 60, Day 90
Secondary	Incidence of abnormal vital signs	vital sign results	Day 30 from baseline or last day in hospital, Day 60, Day 90
Secondary	Incidence of abnormal laboratory results	laboratory results	Day 30 from baseline or last day in hospital, Day 60, Day 90
Secondary	All-cause mortality	All-cause mortality	Day 30 from baseline, Day 60, Day 90
Secondary	Days free of organ failure	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	Day 30 from baseline or last day in study, Day 60, Day 90
Secondary	Days free of renal support		Day 30 from baseline or last day in study
Secondary	Days free of vasoactive support		Day 30 from baseline or last day in study
Secondary	Number of ICU-free days	assessed at Day 30 or on the last day in the ICU if the patient leaves the ICU before Day 30	Day 30 from baseline
Secondary	Days free of invasive mechanical ventilation		Day 30 from baseline of last day in study
Secondary	Length of hospital stay	Number of days in hospital	Study Completion (up to 95 days from baseline)
Secondary	Forced Expiratory Volume (FEV1)		Day 30 from baseline, Day 60 from baseline, Day 90 from baseline
Secondary	Neurological functioning	6 minute walk test	Day 30 from baseline, Day 60 from baseline, Day 90 from baseline
Secondary	PROMIS CAT score (Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive testing (CAT))	0 to 100, with 0 being the lowest physical function and most disabled and 100 having the highest functioning	Day 30 from baseline, Day 60 from baseline, Day 90 from baseline
Secondary	Post concussion symptom scale (PCSS)	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	Day 30 from baseline, Day 60 from baseline, Day 90 from baseline