nVNS for Traumatic Brain Injury-Induced Acute Respiratory Distress

Overseen By Myles Forsyth

Age: Any Age

Sex: Any

Trial Phase: Academic

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

Disqualifiers: Pregnancy, COPD, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: Up to 30 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new device called the gammaCore Sapphire S to assist people with mild-to-moderate traumatic brain injuries (TBI) who risk serious breathing problems. The device uses non-invasive vagus nerve stimulation (nVNS), applying a small device to the neck to reduce inflammation and prevent severe respiratory issues. Participants will receive either this treatment with standard hospital care or standard care alone. Those recently hospitalized for mild-to-moderate TBI, not on a breathing machine, and at risk of lung problems might be suitable for this study. As an unphased trial, this study offers a chance to contribute to innovative research that could enhance future TBI care.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that the nVNS device is safe for use in patients with traumatic brain injury?

Research has shown that the gammaCore Sapphire S device, which uses non-invasive vagus nerve stimulation (nVNS), has been tested in various studies. In one study involving patients with moderate to severe COVID-19, the device showed no serious safety issues, indicating it is generally well-tolerated. Another study tested nVNS for treating PTSD (Post-Traumatic Stress Disorder) symptoms and found it effective without significant side effects.

These results suggest that nVNS is relatively safe, at least in the situations studied. However, this information comes from past studies, not the current trial. Therefore, it is crucial to carefully consider and discuss participation with healthcare providers. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatment?

Researchers are excited about non-invasive vagus nerve stimulation (nVNS) for traumatic brain injury-induced acute respiratory distress because it offers a new approach that could supplement the standard care options, which typically include mechanical ventilation and supportive therapies. Unlike traditional treatments that primarily focus on managing symptoms, nVNS targets the nervous system directly by stimulating the vagus nerve through a simple, non-invasive method. This could potentially reduce inflammation and improve breathing without the need for invasive procedures. Additionally, the ease of administration, which involves just a few minutes of neck stimulation multiple times a day, makes it accessible and convenient for patients and caregivers.

What evidence suggests that the nVNS device is effective for preventing severe respiratory distress in TBI patients?

This trial will compare non-invasive vagus nerve stimulation (nVNS) with standard care for patients experiencing acute respiratory distress due to traumatic brain injury. Studies have shown that nVNS can help with various health issues. For instance, it has successfully eased symptoms of migraines and post-traumatic stress disorder (PTSD). By stimulating a nerve in the neck, nVNS can manage inflammation and stress in the body. This is crucial because brain injuries often lead to severe inflammation and breathing problems. Early research suggests that nVNS might prevent these issues and reduce the need for breathing machines in patients with mild-to-moderate brain injuries. ^{1 2 5 6 7}

Who Is on the Research Team?

Sarah Kimutis

Principal Investigator

Allegheny Health Network

Are You a Good Fit for This Trial?

This trial is for hospitalized patients aged 18-80 with mild-to-moderate traumatic brain injury (TBI) not on mechanical ventilation. They must have a Glasgow Coma Scale score of at least 12 and a Lung Injury Prediction Score of at least 2, indicating potential respiratory issues. Exclusions include severe lung or heart conditions, pregnancy, burns over a large body area, participation in another trial, and certain critical health statuses.

Inclusion Criteria

Your Lung Injury Prediction Score (LIPS) is 2 or higher.

My first nVNS treatment is scheduled within 24 hours of starting.

I had a mild-to-moderate brain injury with a GCS score of 12 or more.

Exclusion Criteria

Patient simultaneously taking part in another clinical trial

You have a medical condition that makes it very likely you will need a breathing machine within 48 hours, or have a condition that might require immediate use of a breathing machine.

I am on a special lung support machine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

1 visit (in-person)

Treatment

Participants receive non-invasive vagus nerve stimulation (nVNS) three times daily along with standard of care for TBI

Up to 30 days

Daily in-hospital monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments at Day 30, Day 60, and Day 90

Up to 95 days

1 visit (in-person) at the end of follow-up period

What Are the Treatments Tested in This Trial?

Interventions

• nVNS

Trial Overview The study tests non-invasive vagus nerve stimulation (nVNS) using the gammaCore Sapphire S device plus standard care against standard care alone to prevent worsening of TBI-induced respiratory distress. The goal is to avoid progression towards severe inflammation and the need for invasive breathing support within the first month after injury.

How Is the Trial Designed?

Group I: Receiving Standard of Care Experimental Treatment 1 Intervention

Patients will be managed according to the institutional best practices and SOC for TBI.

Group II: Receiving Non-invasive vagus neurostimulation Experimental Treatment 2 Interventions

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.

nVNS is already approved in United States for the following indications:

Approved in United States as gammaCore Sapphire for:

• Acute treatment of pain associated with migraine headache
• Acute treatment of pain associated with episodic cluster headache
• Adjunctive use for the preventive treatment of cluster headache
• Emergency use for acute treatment of exacerbation of asthma-related dyspnea and reduced airflow in adult patients with known or suspected COVID-19

Who Is Running the Clinical Trial?

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

Lead Sponsor

Trials

52

Recruited

13,000+

Chuck Noll Foundation

Collaborator

Trials

1

Recruited

50+

ElectroCore INC

Industry Sponsor

Trials

31

Recruited

2,200+

Published Research Related to This Trial

In a study involving 10 immunocompromised patients with acute respiratory failure, the newly developed helmet for non-invasive ventilation (NIV) was well tolerated and led to improved oxygenation within the first 24 hours.

The helmet may provide a safer and more comfortable alternative to traditional endotracheal intubation and standard face masks, as 8 out of 10 patients were successfully weaned from NIV, despite two patients requiring intubation due to septic shock.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and tolerability of non-invasive ventilation delivered via a newly developed helmet in immunosuppressed patients with acute respiratory failure. Rabitsch, W., Schellongowski, P., Köstler, WJ., et al.[2020]

Non-invasive mechanical ventilation (NIV) using a helmet may be a safer and more tolerable alternative to face masks for patients with acute respiratory failure, as indicated by better tolerance in six studies and lower intubation rates in three studies.

While NIV with a helmet showed similar oxygenation levels compared to face masks, it also presented potential issues such as CO₂ rebreathing and increased ventilator asynchrony, highlighting the need for careful patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical review: Helmet and non-invasive mechanical ventilation in critically ill patients. Esquinas Rodriguez, AM., Papadakos, PJ., Carron, M., et al.[2021]

The study found that 30% of patients with isolated severe traumatic brain injury (TBI) developed acute respiratory distress syndrome (ARDS) within the first 8 days, indicating a significant risk associated with this condition.

Factors such as the severity of head injury, male sex, and early transfusion of platelets were linked to a higher risk of ARDS, suggesting that early platelet transfusion could be a modifiable risk factor worth further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The acute respiratory distress syndrome following isolated severe traumatic brain injury. Hendrickson, CM., Howard, BM., Kornblith, LZ., et al.[2022]

Mechanical ventilation is crucial for patients with traumatic brain injuries exhibiting severe symptoms like high intracranial pressure and coma, as it can help manage life-threatening conditions.

In cases of acute respiratory distress syndrome (ARDS), mechanical ventilation is indicated when patients show significant hypoxia and reduced lung capacity, ensuring better oxygenation and respiratory support.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Indications and diagnostic criteria for early ventilation of trauma patients]. Riemenschneider, VT., Junginger, W.[2020]

Neurally adjusted ventilatory assist (NAVA) with neurally controlled pressure support (PSN) significantly improved patient comfort during noninvasive ventilation (NIV) compared to both pneumatically-triggered pressure support (PSP) and NAVA itself, as shown in a study involving 14 patients post-extubation.

PSN also enhanced patient-ventilator interaction and synchrony, with a lower rate of asynchrony compared to PSP, indicating that PSN may be a more effective option for delivering NIV through a facial mask.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New setting of neurally adjusted ventilatory assist for noninvasive ventilation by facial mask: a physiologic study. Longhini, F., Pan, C., Xie, J., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04935697

Non-invasive Vagal Neurostimulation (nVNS) for Traumatic ... This is a prospective, randomized, two-arm, controlled 30-day investigational pilot trial using the gammaCore Sapphire S non-invasive vagus nerve ...

2. withpower.com withpower.com/trial/phase-respiratory-distress-syndrome-4-2021-028df

nVNS for Traumatic Brain Injury-Induced Acute Respiratory ... This trial is testing a device that stimulates a nerve in the neck, along with usual medical care, to help patients with mild-to-moderate brain injuries.

3. electrocore.com electrocore.com/medical-affairs/ptsd/

nVNS for Treating the Symptoms of PTSD nVNS led to significantly greater decreases in long-term heart rate variability over the course of multiple traumatic stress and stimulation protocols.

4. reporter.nih.gov reporter.nih.gov/search/UQ1Jy3NuN0Wo-UIXXw-5zw/project-details/10575817

Project Details - NIH RePORTER Recent clinical trials on the use of non-invasive VNS (nVNS) to treat migraine headaches and post-traumatic stress disorders have shown to be effective.

5. gammacore.com gammacore.com/wp-content/uploads/2022/09/64000-00185-REV-1-gammaCore-Sapphire-Clinical-Studies.pdf

CLINICAL STUDIES The primary efficacy end point in the ACT1 Study was the percentage of patients who reported mild or no pain 15 minutes after treatment initiation with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7316576/

Sapphire device for patients with moderate to severe ... A prospective, randomized, controlled study assessing vagus nerve stimulation using the gammaCore®-Sapphire device for patients with moderate to severe CoViD-19 ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04071743

NCT04071743 | Study of Gammacore Sapphire for the ... The study will enroll 60 subjects over a period of 14 weeks each. Subjects will use either a sham or active device to treat acute Post Traumatic Headache.