Traumatic Brain InjuryPhase 1NCT02974959
Vagus Nerve Stimulation to Treat Moderate Traumatic Brain Injury
A Phase 1 study testing gammaCore active device in people with Traumatic Brain Injury and Acute Brain Injuries, run by CentraCare at 1 site in United States.
Trial summary
The purpose of this single-center, prospective, randomized (1:1), double-blind, sham-controlled parallel-arm pilot study is to provide initial evidence of use of the noninvasive vagus nerve stimulator for treatment in patients recovering from concussion and moderate traumatic brain injury to improve clinical recovery. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Traumatic Brain Injury, Acute Brain Injuries
- What is being tested?
- gammaCore active device
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2016to Nov 2020
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Written Informed Consent obtained by Subject or Subject's proxy.
- Is between the ages of 18 and 60 years, male or female.
- Meets the criteria of the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine, which defines a head injury as a traumatically induced physiologic disruption of brain function, as manifested by one of the following:
- Any period of loss of consciousness (LOC),
- Any loss of memory for events immediately before or after the accident,
- Any alteration in mental state at the time of the accident,
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- Focal neurologic deficits, which may or may not be transient.
- Meets the criteria for moderate TBI as defined by the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine, which are as follows:
- Length of stay at least 48 hours,
- Glasgow Coma Scale (GCS score of 9-12 or higher)
- Operative intracranial lesion,
- Abnormal CT scan findings.
- Has had a craniotomy, but those with hydrocephalus or active intracranial pressure elevation will be excluded.
- Able to accurately communicate the sensation of amplitude of intensity by the stimulation treatment with the GammaCore device.
- Has a stable orthopedic or other traumatic body injury.
- Is capable of completing all study assessments.
- Agrees to use the GammaCore device as intended and follow all of the requirements of the study, including follow-up visits.
- Agrees to record usage of the GammaCore device, all required study data, and report any adverse effects to the sponsor/investigator within 24 hours of any such adverse event.
Who cannot join
- Has an active DNR/DNI (do not resuscitate/ do not intubate) request.
- Has dissent among family members / next of kin regarding level of care.
- Has a penetrating injury.
- Has concurrent active severe medical problems or conditions, which could prevent survival during the course of the study.
- Has pre-existing central nervous system disease or associated comorbidities that may not allow for an 18-week follow-up visit.
- Has an abscess, infection or lesion (including lymphadenopathy) at the gammaCore treatment site.
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- Has known or suspected moderate to severe atherosclerotic cardiovascular disease, carotid artery disease (e.g. bruits or history of TIA or CVA).
- Has a clinically significant irregular heart rate or rhythm.
- Has uncontrolled hypertension (systolic bp > 200 or diastolic bp >100), recent (within the last 3 months) heart attack, recent (within the last 3 months) stroke, known aortic aneurysm, or congestive heart failure (CHF).
- Is currently implanted with an electrical and/or neurostimulator device, including but not limited to cardiac pacemaker, defibrillator, vagal neurostimulator, deep brain stimulator, spinal stimulator, bone growth stimulator, or cochlear implant.
- Has a history of significant carotid endarterectomy, vagotomy, dysaesthesia or vascular neck surgery on either side of the neck.
- Has been implanted with metal cervical spine hardware.
- Has a recent or repeated history of syncope.
- Has a recent or repeated history of seizures.
- Has known clotting disorder or hemophilia
- Has anemia (hb<12)
- Is pregnant or nursing, or of childbearing potential and is unwilling to use an accepted form of birth control (hormonal, barrier method, surgical, or abstention or is at least two years post-menopause).
- Is participating in any other therapeutic clinical investigation or has participated in a clinical trial in the preceding 30 days.
- Is an employee of the clinical study site or a relative of the Investigator.
- Has an abnormal baseline electrocardiogram (ECG), including second and third degree heart block, atrial fibrillation, atrial flutter, recent history of ventricular tachycardia or ventricular fibrillation or clinically significant premature ventricular contraction.
- Has a known history or suspicion of substance abuse or addiction.
Trial locations and contacts
1 site in 1 country.
United States1 site
Hennepin County Medical Center
Minneapolis, Minnesota, 55415
About this study
Official title: Vagus Nerve Stimulation to Treat Mild To Moderate Traumatic Brain Injury
The purpose of this single-center, prospective, randomized (1:1), double-blind, sham-controlled parallel-arm pilot study is to provide initial evidence of use of the noninvasive vagus nerve stimulator for treatment in patients recovering from concussion and moderate traumatic brain injury to improve clinical recovery. The study compares the safety and effectiveness of an active gammaCore treatment against a sham treatment.
Read the detailed description
Our primary aim is to assess for evidence of the effectiveness of the nVNS in reducing clinical symptoms such as motor and cognition deficits. As a primary endpoint, we will analyze the difference between groups at all time points in standardized cognitive assessments. We will also assess the levels of different inflammatory cytokines.
The secondary endpoints for moderate TBI are functional assessments and quality of life questionnaires including a depression screen. Our secondary aim is to assess the safety of a non-invasive VNS (nVNS) in a subset of patients who have suffered a moderate TBI. We do not anticipate any significant difference between heart rate variability (HRV) in active compared to sham treatments and no difference symptoms experienced during treatment sessions.
We propose a single-center, prospective, randomized (1:1), double-blind, sham-controlled, parallel-arm pilot study. We determined that an N of 30 patients would be needed to reach significance. Moderate TBI will be defined by the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine (full list in inclusion criteria) seeking care at HCMC within 2 weeks of injury. Recruited subjects will be randomized to active treatment or sham-treatment control arms. Randomization to active or sham gammaCore treatment will occur during the screening visit after enrollment, and intervention will begin at the baseline visit that occurs 72 hours (+/- 1 day) after enrollment. Informed consent will be obtained from patients or their proxy prior to enrollment. If a proxy elects to enroll a patient, who then recovers during the course of the study, they will be able to withdraw from the study if they so desire. We anticipate enrollment to take approximately 6 months, and enrolled subjects will be followed through the final week 18 follow up visit, estimating a completion date 9 months after the first enrollment.
The treatment will include 12 weeks of active interventional therapy, with seven visits, including the screening visit that takes place within 2 weeks of injury. From the baseline visit, there will be a follow up phone call at 1 week, and a follow up visit at 2, 6, 12 and 18 weeks. During each of these visits, data assessing heart rate variability will be obtained using a chest strap heart rate monitor and a non-invasive heart rate variability monitor will be used to measure minute phenomenon in heartbeats. This will be done while supine, during treatment and after an orthostatic challenge (i.e. standing or sitting upright). An EKG will be obtained at each visit to assess for bradycardia.
The nVNS therapy will be performed using the gammaCore-R (electroCore LLC, NJ), which is an external hand-held vagal nerve stimulator. The gammaCore-R produces a low voltage electric signal consisting of five 5000 Hz pulses that are repeated at a rate of 25 Hz. The strength of the stimulation is lower than that required to activate efferent vagal nerve fibers that mediates cardiac specific effects and will only be used on the left vagus nerve, which has fewer cardiac projections. It allows for a 120 second stimulation session. The stimulation will occur twice daily, one time in the morning and one time in the evening. This should be done as close to 12 hours apart as possible and should occur twice daily for the entire 12 week study period. The sham device appears identical to the gammaCore but does not provide a frequency of stimulation powerful enough to stimulate either efferent or afferent fibers of the vagus nerve. However, it does supply a low frequency current which will cause a tingling of this skin to improve blinding of the patients. After the 12 week visit, the device will be returned. However, both the treating physician and the patient will remain blinded to the study arms until the completion of the study at week 18. Blood samples (10 mL or two teaspoons) will be drawn at the screening visit, as well as the 12 and 18-week time points for biomarker analysis.
- Conditions
- Traumatic Brain Injury, Acute Brain Injuries
- Being tested
- gammaCore active device, gammaCore sham device
- Medical subject headings
- Brain Injuries, Traumatic, Brain Injuries
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gammaCore active deviceDevice
The nVNS therapy will be performed using the gammaCore-R (electroCore LLC, NJ), which is an external hand-held vagal nerve stimulator. The gammaCore-R produces a low voltage electric signal consisting of five 5000 Hz pulses that are repeated at a rate of 25 Hz. It allows for a 120 second stimulation session. The stimulation will occur twice daily, one time in the morning and one time in the evening. This should be done as close to 12 hours apart as possible and should occur twice daily for the entire 12 week study period.
gammaCore sham deviceDevice
The sham device appears identical to the gammaCore but does not provide a frequency of stimulation powerful enough to stimulate either efferent or afferent fibers of the vagus nerve. However, it does supply a low frequency current which will cause a tingling of this skin to improve blinding of the patients.
| Study group | Role | What they receive |
|---|---|---|
| gammaCore active device | Experimental | Patients in this arm will be using an active device which delivers a treatment dose of current to the vagus nerve twice daily for 120 seconds Receives: Device: gammaCore active device |
| gammaCore Sham device | Sham comparator | Patients in this arm will be using a sham device which does not deliver a treatment dose of current, but will deliver enough current to cause tingling on the skin. Receives: Device: gammaCore sham device |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety/bradycardia
We will evaluate for bradycardia after using the device at all time points using an EKG and heart rate variability (Beats/minute for each)
Measured: 18 weeks
Secondary outcomes (3)
Efficacy-cognition
We will assess whether vagus nerve simulation impacts clinical recovery from TBI as assessed by neuro-cognitive assessments
Measured: initial visit, 2 weeks, 6 weeks, 12 weeks, 18 weeks
Efficacy-eye tracking
We will evaluate for changes in eye tracking metrics
Measured: initial visit, 2 weeks, 6 weeks, 12 weeks, 18 weeks
Efficacy-serum biomarkers
Evaluate for changes in serum biomarkers with treatment
Measured: initial visit, 2 weeks, 6 weeks, 12 weeks, 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Nov 2016 (estimated)
- Study startOct 2016
- Primary completionJun 2020
- Study completionNov 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Traumatic Brain InjuryStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized control trial
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- CentraCare
- Sponsor type
- University, hospital or other
- Collaborators
- ElectroCore INC
- Responsible party
- Sponsor
- Investigators
- Uzma Samadani, MD, PhD, Principal investigator, Hennepin County Medical Center, MinneapolisThomas Bergman, MD, Principal investigator, Hennepin County Medical Center, Minneapolis
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02974959
- Sponsor's protocol ID
- HSR 16-4171
- Status last verified
- Feb 2021
- First submitted
- 12 Sep 2016
- Last updated
- 4 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vagus Nerve Stimulation to Treat Mild To Moderate Traumatic Brain Injury
- ClinicalTrials.gov ID
- NCT02974959
- Acronym / sponsor ID
- HSR 16-4171
- Conditions
- Traumatic Brain Injury, Acute Brain Injuries
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- CentraCareUniversity, hospital or other
- Collaborators
- ElectroCore INC
- Study start
- Oct 2016 (actual)
- Primary completion
- Jun 2020 (actual)
- Study completion
- Nov 2020 (actual)
- First posted
- 29 Nov 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this single-center, prospective, randomized (1:1), double-blind, sham-controlled parallel-arm pilot study is to provide initial evidence of use of the noninvasive vagus nerve stimulator for treatment in patients recovering from concussion and moderate traumatic brain injury to improve clinical recovery. The study compares the safety and effectiveness of an active gammaCore treatment against a sham treatment.
Detailed description
Our primary aim is to assess for evidence of the effectiveness of the nVNS in reducing clinical symptoms such as motor and cognition deficits. As a primary endpoint, we will analyze the difference between groups at all time points in standardized cognitive assessments. We will also assess the levels of different inflammatory cytokines.
The secondary endpoints for moderate TBI are functional assessments and quality of life questionnaires including a depression screen. Our secondary aim is to assess the safety of a non-invasive VNS (nVNS) in a subset of patients who have suffered a moderate TBI. We do not anticipate any significant difference between heart rate variability (HRV) in active compared to sham treatments and no difference symptoms experienced during treatment sessions.
We propose a single-center, prospective, randomized (1:1), double-blind, sham-controlled, parallel-arm pilot study. We determined that an N of 30 patients would be needed to reach significance. Moderate TBI will be defined by the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine (full list in inclusion criteria) seeking care at HCMC within 2 weeks of injury. Recruited subjects will be randomized to active treatment or sham-treatment control arms. Randomization to active or sham gammaCore treatment will occur during the screening visit after enrollment, and intervention will begin at the baseline visit that occurs 72 hours (+/- 1 day) after enrollment. Informed consent will be obtained from patients or their proxy prior to enrollment. If a proxy elects to enroll a patient, who then recovers during the course of the study, they will be able to withdraw from the study if they so desire. We anticipate enrollment to take approximately 6 months, and enrolled subjects will be followed through the final week 18 follow up visit, estimating a completion date 9 months after the first enrollment.
The treatment will include 12 weeks of active interventional therapy, with seven visits, including the screening visit that takes place within 2 weeks of injury. From the baseline visit, there will be a follow up phone call at 1 week, and a follow up visit at 2, 6, 12 and 18 weeks. During each of these visits, data assessing heart rate variability will be obtained using a chest strap heart rate monitor and a non-invasive heart rate variability monitor will be used to measure minute phenomenon in heartbeats. This will be done while supine, during treatment and after an orthostatic challenge (i.e. standing or sitting upright). An EKG will be obtained at each visit to assess for bradycardia.
The nVNS therapy will be performed using the gammaCore-R (electroCore LLC, NJ), which is an external hand-held vagal nerve stimulator. The gammaCore-R produces a low voltage electric signal consisting of five 5000 Hz pulses that are repeated at a rate of 25 Hz. The strength of the stimulation is lower than that required to activate efferent vagal nerve fibers that mediates cardiac specific effects and will only be used on the left vagus nerve, which has fewer cardiac projections. It allows for a 120 second stimulation session. The stimulation will occur twice daily, one time in the morning and one time in the evening. This should be done as close to 12 hours apart as possible and should occur twice daily for the entire 12 week study period. The sham device appears identical to the gammaCore but does not provide a frequency of stimulation powerful enough to stimulate either efferent or afferent fibers of the vagus nerve. However, it does supply a low frequency current which will cause a tingling of this skin to improve blinding of the patients. After the 12 week visit, the device will be returned. However, both the treating physician and the patient will remain blinded to the study arms until the completion of the study at week 18. Blood samples (10 mL or two teaspoons) will be drawn at the screening visit, as well as the 12 and 18-week time points for biomarker analysis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized control trial
| Arm | Type | Receives |
|---|---|---|
| gammaCore active device | Experimental | Device: gammaCore active devicePatients in this arm will be using an active device which delivers a treatment dose of current to the vagus nerve twice daily for 120 seconds |
| gammaCore Sham device | Sham comparator | Device: gammaCore sham devicePatients in this arm will be using a sham device which does not deliver a treatment dose of current, but will deliver enough current to cause tingling on the skin. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (18 listed)
- Written Informed Consent obtained by Subject or Subject's proxy.
- Is between the ages of 18 and 60 years, male or female.
- Meets the criteria of the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine, which defines a head injury as a traumatically induced physiologic disruption of brain function, as manifested by one of the following:
- Meets the criteria for moderate TBI as defined by the Head Injury Interdisciplinary Special Interest Group of the American Congress of Rehabilitation Medicine, which are as follows:
- Has had a craniotomy, but those with hydrocephalus or active intracranial pressure elevation will be excluded.
Key exclusion criteria (21 listed)
- Has an active DNR/DNI (do not resuscitate/ do not intubate) request.
- Has dissent among family members / next of kin regarding level of care.
- Has a penetrating injury.
- Has concurrent active severe medical problems or conditions, which could prevent survival during the course of the study.
- Has pre-existing central nervous system disease or associated comorbidities that may not allow for an 18-week follow-up visit.
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 |
|---|---|---|
| gammaCore active deviceThe nVNS therapy will be performed using the gammaCore-R (electroCore LLC, NJ), which is an external hand-held vagal nerve stimulator. The gammaCore-R produces a low voltage electric signal consisting of five 5000 Hz pulses that are repeated at a rate of 25 Hz. It allows for a 120 second stimulation session. The stimulation will occur twice daily, one time in the morning and one time in the evening. This should be done as close to 12 hours apart as possible and should occur twice daily for the entire 12 week study period. | Device | gammaCore active device |
| gammaCore sham deviceThe sham device appears identical to the gammaCore but does not provide a frequency of stimulation powerful enough to stimulate either efferent or afferent fibers of the vagus nerve. However, it does supply a low frequency current which will cause a tingling of this skin to improve blinding of the patients. | Device | gammaCore Sham device |
Primary outcome
Safety/bradycardia
Time frame: 18 weeks
We will evaluate for bradycardia after using the device at all time points using an EKG and heart rate variability (Beats/minute for each)
3 secondary outcomes
Efficacy-cognition
Time frame: initial visit, 2 weeks, 6 weeks, 12 weeks, 18 weeks
Efficacy-eye tracking
Time frame: initial visit, 2 weeks, 6 weeks, 12 weeks, 18 weeks
Efficacy-serum biomarkers
Time frame: initial visit, 2 weeks, 6 weeks, 12 weeks, 18 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2021.
- Individual participant dataSharing planned: Undecided
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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.
Uzma Samadani, MD, PhD principal investigator
Hennepin County Medical Center, Minneapolis
Thomas Bergman, MD principal investigator
Hennepin County Medical Center, Minneapolis
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing gammaCore active device in people with Traumatic Brain Injury and Acute Brain Injuries, run by CentraCare 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 18 inclusion and 21 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 4 Feb 2021. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Safety/bradycardia (time frame: 18 weeks). 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 4 Feb 2021.