Acute Respiratory Distress SyndromeNCT04935697
Non-invasive Vagal Neurostimulation (nVNS) for Traumatic Brain Injury (TBI)-Induced Acute Respiratory Distress
A study testing nVNS and SOC in people with Acute Respiratory Distress Syndrome and Acute Lung Injury, run by Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) at 1 site in United States.
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… Read more about this study
- Who is it for?
- Ages 12 to 80 years
- Conditions the study is for
- Acute Respiratory Distress Syndrome, Acute Lung Injury, Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)
- What is being tested?
- nVNS and SOC
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Aug 2021to 1 Mar 2025
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 12 to 80 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patient is between 12-80 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
- Patient has a Lung Injury Prediction Score (LIPS) of =>2
- 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
Who cannot join
- 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)
- Woman known to be pregnant, lactating or with a positive (urine or serum test) or indeterminate (serum test) pregnancy test
- Patient simultaneously taking part in another clinical trial
- Patient is not expected to survive for 24 hours
- 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
Show all 13Show fewer
- Patient has congestive heart failure
- Patient has acute left ventricular failure
- Patient has liver failure (Child-Pugh grade C)
- Patient is receiving renal dialysis therapy for chronic renal failure
- Patient is receiving extracorporeal membrane oxygenation, high-frequency oscillatory ventilation (HFOV) or any form of extracorporeal lung support
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
AHN Allegheny General Hospital
Pittsburgh, Pennsylvania, 15212
About this study
Official title: 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).
Read the 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.
- Conditions
- Acute Respiratory Distress Syndrome, Acute Lung Injury, Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS), Traumatic Brain Injury
- Being tested
- nVNS, SOC
- Keywords
- Non-invasive Vagal Nerve Stimulation
- Medical subject headings
- Respiratory Distress Syndrome, Acute Lung Injury, Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
nVNSDevice
3x daily treatment of nVNS + SOC
SOCOther
Standard of care patient management.
| Study group | Role | What they receive |
|---|---|---|
| Receiving Non-invasive vagus neurostimulation | Experimental | 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. Receives: Device: nVNS; Other: SOC |
| Receiving Standard of Care | Other | Patients will be managed according to the institutional best practices and SOC for TBI. Receives: Other: SOC |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 90 days
Secondary outcomes (4)
Number of Participants With AEs/SAEs Up to 30 Days From Baseline
Measured: 30 days from baseline
Number of Participants With Abnormal Physical Examination by Day 30
Measured: 30 days from baseline
Number of Participants With Abnormal Vital Signs by Day 30
Measured: 30 days from baseline
Number of Participants With Abnormal Laboratory Results by Day 30
Measured: 30 days from baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jun 2021
- Study start4 Aug 2021
- Primary completion1 Mar 2025
- Study completion1 Mar 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
- Sponsor type
- University, hospital or other
- Collaborators
- ElectroCore INC, Chuck Noll Foundation
- Responsible party
- Principal investigator, Edward Snell, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)
- Investigators
- Sarah Kimutis, Study director, Allegheny Health Network
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04935697
- Sponsor's protocol ID
- nVNS for TBI-ALI/ARDS
- Status last verified
- May 2026
- First submitted
- 12 Mar 2021
- Last updated
- 29 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non-invasive Vagal Neurostimulation (nVNS) to Mitigate Traumatic Brain Injury (TBI)-Induced Acute Respiratory Distress and Acute Lung Injury
- ClinicalTrials.gov ID
- NCT04935697
- Acronym / sponsor ID
- nVNS for TBI-ALI/ARDS
- 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
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)University, hospital or other
- Collaborators
- ElectroCore INC, Chuck Noll Foundation
- Study start
- 4 Aug 2021 (actual)
- Primary completion
- 1 Mar 2025 (actual)
- Study completion
- 1 Mar 2025 (actual)
- First posted
- 23 Jun 2021 (actual)
- Results
- Posted 29 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Receiving Non-invasive vagus neurostimulation | Experimental | Device: nVNS, Other: SOCnVNS 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. |
| Receiving Standard of Care | Other | Other: SOCPatients will be managed according to the institutional best practices and SOC for TBI. |
Who may qualify
- Ages
- 12 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patient is between 12-80 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
- Patient has a Lung Injury Prediction Score (LIPS) of =>2
Key exclusion criteria (13 listed)
- 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)
- Woman known to be pregnant, lactating or with a positive (urine or serum test) or indeterminate (serum test) pregnancy test
- Patient simultaneously taking part in another clinical trial
- Patient is not expected to survive for 24 hours
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| nVNS3x daily treatment of nVNS + SOC | Device | Receiving Non-invasive vagus neurostimulation |
| SOCStandard of care patient management. | Other | Receiving Non-invasive vagus neurostimulation, Receiving Standard of Care |
Primary outcome
All-Cause 90-Day Admission to Any Hospital or ED Encounter
Time frame: 90 days
A composite endpoint of 90-day presentation to any emergency department and/or 90-day admission to any hospital.
4 secondary outcomes
Number of Participants With AEs/SAEs Up to 30 Days From Baseline
Time frame: 30 days from baseline
Number of Participants With Abnormal Physical Examination by Day 30
Time frame: 30 days from baseline
Number of Participants With Abnormal Vital Signs by Day 30
Time frame: 30 days from baseline
Number of Participants With Abnormal Laboratory Results by Day 30
Time frame: 30 days from baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
Related trials for Acute Respiratory Distress Syndrome
Enrolling by invitation
Personalized Ventilator Settings for Patients on ECMO
Acute Respiratory Distress Syndrome (ARDS), Extracorporeal Membrane Oxygenation
Active, not recruiting
CT for Personalized Mechanical Ventilation
Ventilator-Induced Lung Injury, Sepsis Syndrome
Not yet recruitingObservational study
Development and Multicenter Validation of an Explainable System for Neonatal ARDS-Compatible Phenotyping
Acute Respiratory Distress Syndrome
RecruitingObservational study
Assessment of Blood Viscosity in ARDS (Acute Respiratory Distress Syndrome)
ARDS
Recruiting
Comparing Surfactant Administration Through Supraglottic Airway and Thin Catheter for Preterm Infants
Surfactant, Respiratory Distress Syndrome (Neonatal)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sarah Kimutis study director
Allegheny Health Network
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing nVNS and SOC in people with Acute Respiratory Distress Syndrome and Acute Lung Injury, run by Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
All-Cause 90-Day Admission to Any Hospital or ED Encounter (time frame: 90 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 May 2026.