Vagus Nerve Stimulation to Treat Moderate Traumatic Brain Injury
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|ClinicalTrials.gov Identifier: NCT02974959|
Recruitment Status : Completed
First Posted : November 29, 2016
Last Update Posted : February 4, 2021
|Condition or disease||Intervention/treatment||Phase|
|Traumatic Brain Injury Acute Brain Injuries||Device: gammaCore active device Device: gammaCore sham device||Phase 1|
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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||14 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||Randomized control trial|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Only the study coordinator had access to the master list which noted whether the device was active or a sham. This information was not provided to or accessible by the participants, care providers, investigators, or outcome assessors.|
|Official Title:||Vagus Nerve Stimulation to Treat Mild To Moderate Traumatic Brain Injury|
|Actual Study Start Date :||October 2016|
|Actual Primary Completion Date :||June 2020|
|Actual Study Completion Date :||November 2020|
Experimental: gammaCore active device
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
Device: gammaCore active device
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.
Sham Comparator: gammaCore Sham device
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.
Device: gammaCore sham device
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.
- 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)
- Efficacy-cognition [ Time Frame: initial visit, 2 weeks, 6 weeks, 12 weeks, 18 weeks ]We will assess whether vagus nerve simulation impacts clinical recovery from TBI as assessed by neuro-cognitive assessments
- Efficacy-eye tracking [ Time Frame: initial visit, 2 weeks, 6 weeks, 12 weeks, 18 weeks ]We will evaluate for changes in eye tracking metrics
- Efficacy-serum biomarkers [ Time Frame: initial visit, 2 weeks, 6 weeks, 12 weeks, 18 weeks ]Evaluate for changes in serum biomarkers with treatment
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02974959
|United States, Minnesota|
|Hennepin County Medical Center|
|Minneapolis, Minnesota, United States, 55415|
|Principal Investigator:||Uzma Samadani, MD, PhD||Hennepin County Medical Center, Minneapolis|
|Principal Investigator:||Thomas Bergman, MD||Hennepin County Medical Center, Minneapolis|