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

Primary Purpose

Acute Respiratory Distress Syndrome, Acute Lung Injury, Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS)

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

nVNS

SOC

About this trial

This is an interventional treatment trial for Acute Respiratory Distress Syndrome focused on measuring Non-invasive Vagal Nerve Stimulation

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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
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

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)
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
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

Sites / Locations

AHN Allegheny General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

nVNS

SOC only

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Days free of invasive mechanical ventilation

Days free of invasive mechanical ventilation within 30 days from baseline among TBI survivors.

Days free of death

Days free of death within 30 days from baseline

Secondary Outcome Measures

Adverse Events/Serious Adverse Events (AEs/SAEs)

Incidence, rate and severity of AEs/SAEs

Incidence of abnormal Physical examinations

Physical examination results

Incidence of abnormal vital signs

vital sign results

Incidence of abnormal laboratory results

laboratory results

All-cause mortality

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

Days free of renal support

Days free of vasoactive support

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

Days free of invasive mechanical ventilation

Length of hospital stay

Number of days in hospital

Forced Expiratory Volume (FEV1)

Neurological functioning

6 minute walk test

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

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

Full Information

NCT ID

NCT04935697

First Posted

March 12, 2021

Last Updated

March 2, 2023

Sponsor

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

Collaborators

ElectroCore INC, Chuck Noll Foundation

1. Study Identification

Unique Protocol Identification Number

NCT04935697

Brief Title

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

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Recruiting

Study Start Date

August 4, 2021 (Actual)

Primary Completion Date

December 2025 (Anticipated)

Study Completion Date

December 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

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

Collaborators

ElectroCore INC, Chuck Noll Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. 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).

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Respiratory Distress Syndrome, Acute Lung Injury, Acute Lung Injury/Acute Respiratory Distress Syndrome (ARDS), Traumatic Brain Injury

Keywords

Non-invasive Vagal Nerve Stimulation

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

46 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

nVNS

Arm Type

Experimental

Arm Description

Arm Title

SOC only

Arm Type

Other

Arm Description

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

Intervention Type

Device

Intervention Name(s)

nVNS

Intervention Description

3x daily treatment of nVNS + SOC

Intervention Type

Other

Intervention Name(s)

SOC

Intervention Description

Standard of care patient management.

Primary Outcome Measure Information:

Title

Days free of invasive mechanical ventilation

Description

Days free of invasive mechanical ventilation within 30 days from baseline among TBI survivors.

Time Frame

30 days from baseline

Title

Days free of death

Description

Days free of death within 30 days from baseline

Time Frame

30 days from baseline

Secondary Outcome Measure Information:

Title

Adverse Events/Serious Adverse Events (AEs/SAEs)

Description

Incidence, rate and severity of AEs/SAEs

Time Frame

Day 30 from baseline, Day 60, Day 90

Title

Incidence of abnormal Physical examinations

Description

Physical examination results

Time Frame

Day 30 from baseline or last day in hospital, Day 60, Day 90

Title

Incidence of abnormal vital signs

Description

vital sign results

Time Frame

Day 30 from baseline or last day in hospital, Day 60, Day 90

Title

Incidence of abnormal laboratory results

Description

laboratory results

Time Frame

Day 30 from baseline or last day in hospital, Day 60, Day 90

Title

All-cause mortality

Description

All-cause mortality

Time Frame

Day 30 from baseline, Day 60, Day 90

Title

Days free of organ failure

Description

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

Time Frame

Day 30 from baseline or last day in study, Day 60, Day 90

Title

Days free of renal support

Time Frame

Day 30 from baseline or last day in study

Title

Days free of vasoactive support

Time Frame

Day 30 from baseline or last day in study

Title

Number of ICU-free days

Description

assessed at Day 30 or on the last day in the ICU if the patient leaves the ICU before Day 30

Time Frame

Day 30 from baseline

Title

Days free of invasive mechanical ventilation

Time Frame

Day 30 from baseline of last day in study

Title

Length of hospital stay

Description

Number of days in hospital

Time Frame

Study Completion (up to 95 days from baseline)

Title

Forced Expiratory Volume (FEV1)

Time Frame

Day 30 from baseline, Day 60 from baseline, Day 90 from baseline

Title

Neurological functioning

Description

6 minute walk test

Time Frame

Day 30 from baseline, Day 60 from baseline, Day 90 from baseline

Title

PROMIS CAT score (Patient-Reported Outcomes Measurement Information System (PROMIS) computer adaptive testing (CAT))

Description

0 to 100, with 0 being the lowest physical function and most disabled and 100 having the highest functioning

Time Frame

Day 30 from baseline, Day 60 from baseline, Day 90 from baseline

Title

Post concussion symptom scale (PCSS)

Description

Time Frame

Day 30 from baseline, Day 60 from baseline, Day 90 from baseline

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility 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 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 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) 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 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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Boyle Cheng, PhD

Phone

412-359-4020

Boyle.Cheng@ahn.org

First Name & Middle Initial & Last Name or Official Title & Degree

Tibetha Santucci, RN

Phone

412-359-8721

tibetha.santucci@ahn.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Boyle Cheng, PhD

Organizational Affiliation

Allegheny Health Network

Official's Role

Principal Investigator

Facility Information:

Facility Name

AHN Allegheny General Hospital

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15212

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Boyle Cheng, PhD

Phone

412-359-4020

boyle.cheng@ahn.org

First Name & Middle Initial & Last Name & Degree

Tibetha Santucci, RN

Phone

412-359-8721

tibetha.santucci@ahn.org

First Name & Middle Initial & Last Name & Degree

Boyle Cheng, PhD

First Name & Middle Initial & Last Name & Degree

Obiad Ashraf, MD

First Name & Middle Initial & Last Name & Degree

Tariq Cheema, MD

First Name & Middle Initial & Last Name & Degree

Justin Davanzo, MD

First Name & Middle Initial & Last Name & Degree

Nick Giannoukakis, PhD

First Name & Middle Initial & Last Name & Degree

Edward Snell, MD

First Name & Middle Initial & Last Name & Degree

Jennifer Chen, MD

First Name & Middle Initial & Last Name & Degree

Allan Philp, MD

First Name & Middle Initial & Last Name & Degree

William Rieck, DO

First Name & Middle Initial & Last Name & Degree

Alexander Yu, MD

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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