Clinical trial NCT05390580: Neuromodulation Using Vagus Nerve Stimulation Following Ischemic Stroke as Therapeutic Adjunct
Official title: Neuromodulation Using Vagus Nerve Stimulation Following Ischemic Stroke as Therapeutic Adjunct
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Acute Ischemic Stroke
Keywords: acute ischemic stroke
cytokines
large vessel occlusion
vagal nerve stimulator
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2022-05-25
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Intervention model description: This is a randomized open-label, with blinded outcome pilot study to evaluate the effect on inflammatory laboratory values and explore clinical outcomes in patients who present with ischemic strokes due to large vessel occlusions and are treated with either current accepted management, or accepted management in addition to transcutaneous auricular vagal nerve stimulation.
Primary purpose: TREATMENT

Brief summary: This is a randomized open-label, with blinded outcome pilot study to evaluate the effect on inflammatory laboratory values and explore clinical outcomes in patients who present with ischemic strokes due to large vessel occlusions and are treated with either current accepted management, or accepted management in addition to transcutaneous auricular vagal nerve stimulation.

Detailed description: Stroke is a leading cause of death and disability worldwide. Approximately 80% of strokes are caused by cerebral ischemia. Although stroke is the third leading cause of death after heart disease and cancer, it leads to permanent disabilities in 80% of survivors. Large vessel occlusions (LVOs) account for up to 38% of acute ischemic strokes (AIS). LVOs represent a clinically significant subpopulation of cerebral ischemia due to their disproportionate morbidity and mortality without treatment. Up to 64% of patients without treatment of their LVO are dead or dependent at 3-6 months. Even after successful treatment (recanalization), infarcts can continue to increase in size, a process referred to as ischemia-reperfusion injury, for which even patients who are successfully treated in the acute setting can have poor outcomes. Highlighting the need for adjunct therapies to minimize ischemia progression for both post recanalized and unrecanalized patients. Neuroinflammation has long been recognized as an important element of AIS pathology. In the acute phase of AIS, non-specific inflammatory markers such as C reactive protein, and classical pro-inflammatory cytokines are elevated and have been associated with aggravating brain injury.

An interesting avenue of research has now aimed to better understand, and eventually to target these inflammatory pathways to improve outcomes after AIS, with anti-inflammatory interventions trialed in humans. Although ongoing trials are occurring in AIS, the immunomodulation agents can be costly and have marked side effects, for which finding adjunct treatments that are easy to administer and with minimal side effects is of the utmost importance. Vagal nerve stimulation (VNS) has previously been established to have anti-inflammatory effects, and has been successfully demonstrated in other models of inflammatory conditions. Given these promising results in animal studies of AIS, and the established safety of the noninvasive transcutaneous auricular VNS (taVNS), the authors propose prospectively studying this non-morbid and safe intervention in our AIS patients due to LVO population at Barnes Jewish Hospital. Our central hypothesis is that implementing transcutaneous auricular vagal nerve stimulation (taVNS) in the acute period following an ischemic stroke due to a large vessel occlusion will attenuate the expected inflammatory response to the stroke and will curtail morbidity associated with inflammatory-mediated clinical endpoints (i.e., infarct progression). The investigators aim to determine if inflammatory markers in the blood are impacted in patients treated with noninvasive VNS, and as a secondary outcome track patient outcomes to better understand the impact on morbidity and mortality.

Patients enrolled in the trial will be randomized to treatment with electrical stimulation to the auricular branch of the vagus nerve (intervention) or stimulation to the great auricular nerve (cervical nerve branch)(Sham) via an auricular, transcutaneous vagus nerve stimulator. All patients will be fitted with the device, the investigators will attach adhesive contacts to the left ear. Stimulation sessions will occur for 20 minutes twice daily during the inpatient period. Patients will have electricity applied to the different nerves depending on the randomization, they will be treated with stimulation with the following parameters: frequency 20 Hz, pulse width 250 µm, and a fixed intensity of 0.5 milliampere. The amplitude of stimulation may be reduced if a patient complains of discomfort at the site of stimulation. The site of stimulation will be inspected daily before and after treatment to ensure there is no redness or irritation at the site. The investigators will obtain laboratory samples on admission, day 0, and every 1.5 days till day 5 or discharge (whichever occurs first) to assess the patients inflammatory markers.

Eligibility criteria: Inclusion Criteria:

* Adult patients who present with acute ischemic strokes due to large vessel occlusions

Exclusion Criteria:

* \<18 years old
* patients with presumed chronic large vessel occlusions
* NIHSS\<6
* pre-morbid modified Rankin score (mRS) \>2
* unable to initiate treatment under 36 hours from symptom discovery
* Chronic or severe infection
* life expectancy \<3 months
* patients' undergoing active cancer or immunosuppressive/modulating therapy
* patients with sustained bradycardia on arrival with a heart rate \<50 beats per minute.

Primary outcomes:
measure: Interleukin - 1b - Changes and differences in the levels
timeFrame: 5 days
measure: Interleukin - 6 - Changes and differences in the levels
timeFrame: 5 days
measure: Tumor necrosis factor alpha - Changes and differences in the levels
timeFrame: 5 days
measure: White blood cell total count - Changes and differences in the levels
timeFrame: 5 days
measure: Neutrophil to lymphocyte ratio - Changes and differences in the levels
timeFrame: 5 days
Secondary outcomes:
measure: Change in NIH Stroke Scale (NIHSS)
timeFrame: 30 days
measure: Modified Ranking Scale (mRS)
timeFrame: 90 days
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 - Hypotension (C143352)
timeFrame: 5 days
measure: Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 - Sinus Bradycardia (C54940)
timeFrame: 5 days
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University in St. Louis School of Medicine
state: Missouri
Study officials:
References: