Intracerebral Hemorrhage
Conditions
Keywords
vagal nerve stimulation, pathologic processes, intracerebral hemmorrhage, cerebrovascular disorders, brain diseases, Central Nervous System Diseases, Nervous System Diseases, Vascular Diseases, Hemorrhage
Brief summary
This study will evaluate whether non-invasive auricular vagal nerve stimulation lowers inflammatory markers, and improves outcomes following intracerebral hemorrhage.
Detailed description
Vagal nerve stimulation (VNS) has been studied as a novel method of reducing inflammation, and it has been successfully used in animal models of inflammatory conditions. The purpose of the proposed study is to determine if transcutaneous auricular VNS will impact inflammatory markers in the blood and cerebrospinal fluid (CSF) in patients with intracerebral hemorrhage, and how it impacts their clinical course and outcomes. This study will involve randomizing patients to stimulation with VNS, or sham stimulation. Blood and CSF will be collected on admission, and serially throughout the patient's admission. Clinical events tracked during the hospital stay include the development of peri-hematomal edema, interventions for edema (medical or surgical), and intensive care unit and hospital stay. Outcomes following admission will include functional scores at discharge, and at follow-up visits for up to 2 years after discharge. No additional appointments will be made specially for the research study.
Interventions
Transcutaneous auricular vagal nerve stimulation
Transcutaneous auricular vagal nerve ear clip applied without current
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Masking description
All participants will be fitted with an auricular stimulator, but blinded to whether they are receiving stimulation or not. Outcome scores will be assessed and recorded by clinicians blinded to treatment arm.
Intervention model description
Participants are assigned to either stimulation or sham stimulation arms
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Adult patients who present with a spontaneous supratentorial intracerebral hemorrhage (ICH) to Barnes Jewish Hospital
Exclusion criteria
* Patients \< 18 years old * Patients with a presumed traumatic etiology for their ICH, infratentorial location, ICH volume \> 60 ml or \< 10 ml, at risk of imminent death (e.g. Glasgow Coma Scale, GCS of 3 or one or more pupils unreactive), surgical intervention imminently planned (not including ventriculostomy) * Patients undergoing active cancer therapy * Patients with sustained bradycardia on arrival with a heart rate \< 50 beats per minute. * Patients who cannot be enrolled within 48 hours of the initial bleed.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in the inflammatory marker IL-6 in plasma | 14 days | Blood samples collected on days 1, 4, 7, 10, and 14 (Day 1 serves as baseline, prior to first treatment). Inflammatory markers will be reported in pg/mL. |
| Growth of perihematomal edema | 14 days | Change in edema extension distance (baseline vs. peak) will be compared between groups, via quantitative assessment of serial computed tomography (CT) scans obtained on day 1, 4, 7, 10, and 14 (Day 1 serves as baseline, prior to first treatment). |
| Neurological worsening | Through hospital admission, average 14 days | Occurrence of clinical deterioration due to edema by criteria of 1) a reduction in GCS by 2 points or greater that persists for at least one hour, 2) worsening focal neurological deficits (NIHSS increase by at least 4 points), excluding other causes, or 3) need for surgical intervention or medical treatments for edema (osmotic therapies). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in additional inflammatory markers in plasma | 14 days | Blood samples collected on days 1, 4, 7, 10, and 14 to evaluate for IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17a, GM-CSF, IFN gamma, and TNF-α. Inflammatory markers will be reported in pg/mL. |
| Change in inflammatory markers in cerebrospinal fluid | 14 days | Cerebrospinal fluid samples collected on days 1, 4, 7, 10, and 14 to evaluate for IL-1b, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17a, GM-CSF, IFN gamma, and TNF-α. Inflammatory markers will be reported in pg/mL. |
| Relative perihematomal edema | 14 days | Relative perihematomal edema volume, the ratio of perihematoma volume to intracerebral hematoma volume |
| Neurological outcome | 2 years | Modified Rankin Scale for Neurological Disability (minimum score 0, maximum score 6, better outcomes have lower scores) |
| Hospital length of stay | Through hospital admission, average 14 days | Total length of stay in the hospital, and in the intensive care unit |
Countries
United States
Contacts
CONTACTRaj Dhar, MD
STUDY_CHAIREric Leuthardt, MD MBA
Washington University School of Medicine
Outcome results
None listed