Clinical trial NCT04935697: Non-invasive Vagal Neurostimulation (nVNS) for Traumatic Brain Injury (TBI)-Induced Acute Respiratory Distress
Official title: Non-invasive Vagal Neurostimulation (nVNS) to Mitigate Traumatic Brain Injury (TBI)-Induced Acute Respiratory Distress and Acute Lung Injury
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
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
Lead sponsor: Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
Sponsor class: OTHER
Collaborators: name: ElectroCore INC
name: Chuck Noll Foundation
First posted: 2021-06-23
Enrollment: 46
Sex: ALL
Minimum age (years): 12
Maximum age (years): 80
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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

Primary outcomes:
measure: Days free of invasive mechanical ventilation
timeFrame: 30 days from baseline
measure: Days free of death
timeFrame: 30 days from baseline
Secondary outcomes:
measure: Adverse Events/Serious Adverse Events (AEs/SAEs)
timeFrame: Day 30 from baseline, Day 60, Day 90
measure: Incidence of abnormal Physical examinations
timeFrame: Day 30 from baseline or last day in hospital, Day 60, Day 90
measure: Incidence of abnormal vital signs
timeFrame: Day 30 from baseline or last day in hospital, Day 60, Day 90
measure: Incidence of abnormal laboratory results
timeFrame: Day 30 from baseline or last day in hospital, Day 60, Day 90
measure: All-cause mortality
timeFrame: Day 30 from baseline, Day 60, Day 90
measure: Days free of organ failure
timeFrame: Day 30 from baseline or last day in study, Day 60, Day 90
measure: Days free of renal support
timeFrame: Day 30 from baseline or last day in study
measure: Days free of vasoactive support
timeFrame: Day 30 from baseline or last day in study
measure: Number of ICU-free days
timeFrame: Day 30 from baseline
measure: Days free of invasive mechanical ventilation
timeFrame: Day 30 from baseline of last day in study
measure: Length of hospital stay
timeFrame: Study Completion (up to 95 days from baseline)
measure: Forced Expiratory Volume (FEV1)
timeFrame: Day 30 from baseline, Day 60 from baseline, Day 90 from baseline
measure: Neurological functioning
timeFrame: Day 30 from baseline, Day 60 from baseline, Day 90 from baseline
measure: PROMIS CAT score (Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive testing (CAT))
timeFrame: Day 30 from baseline, Day 60 from baseline, Day 90 from baseline
measure: Post concussion symptom scale (PCSS)
timeFrame: Day 30 from baseline, Day 60 from baseline, Day 90 from baseline
Other outcomes:
Locations:
city: Pittsburgh
country: United States
facility: AHN Allegheny General Hospital
state: Pennsylvania
Study officials:
affiliation: Allegheny Health Network
name: Sarah Kimutis
role: STUDY_DIRECTOR
References: