Non-invasive Vagal Neurostimulation (nVNS) for Traumatic Brain Injury (TBI)-Induced Acute Respiratory Distress
Study Details
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 |
|---|---|---|
|
N/A |
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
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.
|
| Other: 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
- Days free of invasive mechanical ventilation [30 days from baseline]
Days free of invasive mechanical ventilation within 30 days from baseline among TBI survivors.
- Days free of death [30 days from baseline]
Days free of death within 30 days from baseline
Secondary Outcome Measures
- Adverse Events/Serious Adverse Events (AEs/SAEs) [Day 30 from baseline, Day 60, Day 90]
Incidence, rate and severity of AEs/SAEs
- Incidence of abnormal Physical examinations [Day 30 from baseline or last day in hospital, Day 60, Day 90]
Physical examination results
- Incidence of abnormal vital signs [Day 30 from baseline or last day in hospital, Day 60, Day 90]
vital sign results
- Incidence of abnormal laboratory results [Day 30 from baseline or last day in hospital, Day 60, Day 90]
laboratory results
- All-cause mortality [Day 30 from baseline, Day 60, Day 90]
All-cause mortality
- Days free of organ failure [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
- Days free of renal support [Day 30 from baseline or last day in study]
- Days free of vasoactive support [Day 30 from baseline or last day in study]
- Number of ICU-free days [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
- Days free of invasive mechanical ventilation [Day 30 from baseline of last day in study]
- Length of hospital stay [Study Completion (up to 95 days from baseline)]
Number of days in hospital
- Forced Expiratory Volume (FEV1) [Day 30 from baseline, Day 60 from baseline, Day 90 from baseline]
- Neurological functioning [Day 30 from baseline, Day 60 from baseline, Day 90 from baseline]
6 minute walk test
- PROMIS CAT score (Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive testing (CAT)) [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
- Post concussion symptom scale (PCSS) [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
Criteria
Inclusion Criteria:
-
Patient is between 18-80 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
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Patient has a Lung Injury Prediction Score (LIPS) of =>2
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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
Exclusion Criteria:
-
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)
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Woman known to be pregnant, lactating or with a positive (urine or serum test) or indeterminate (serum test) pregnancy test
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Patient simultaneously taking part in another clinical trial
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Patient is not expected to survive for 24 hours
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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
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Patient has congestive heart failure
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Patient has acute left ventricular failure
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Patient has liver failure (Child-Pugh grade C)
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Patient is receiving renal dialysis therapy for chronic renal failure
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Patient is receiving extracorporeal membrane oxygenation, high-frequency oscillatory ventilation (HFOV) or any form of extracorporeal lung support
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | AHN Allegheny General Hospital | Pittsburgh | Pennsylvania | United States | 15212 |
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
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- nVNS for TBI-ALI/ARDS