Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis (NERINASEPSIS)

University of Oklahoma (OU)

Status: Enrolling

Conditions: Septic Shock

Treatments: Device: Low Level Transcutaneous Vagus Nerve Stimulation

Study type: Interventional

Funder types: Other; Other U.S. Federal agency

Identifiers

NCT03992378

9227 (Registry Identifier)

Details and patient eligibility

About

Sepsis is life-threatening organ dysfunction caused by a dysregulated host response to infection. It is the most expensive healthcare condition to treat in United States and has a mortality rate of nearly 30%. It is widely known that exaggerated inflammation and imbalance between sympathetic and parasympathetic arms of the autonomic nervous system (ANS) contribute to progression and adverse outcomes in sepsis. The role of unchecked inflammation and unregulated ANS as a potential treatment target is an important gap in our knowledge that should be explored.

Cholinergic anti-inflammatory pathway (CAP) is an intricate network where the ANS senses inflammation by vagus nerve afferents and tries to regulate it by vagus nerve efferents to the reticuloendothelial system. The central hypothesis of this pilot clinical trial is that transcutaneous vagus nerve stimulation (TVNS) at tragus of the external ear can activate the CAP to suppress inflammation and improve autonomic imbalance as measured by inflammatory cytokine levels and heart rate variability (HRV) analysis. The investigators plan to randomize patients with septic shock into active and sham stimulation groups and study the effects of vagal stimulation on inflammatory cytokines, HRV and a clinical severity score of sepsis. Both groups will continue to receive the standard of care treatment for sepsis irrespective of group assignments. The investigators hypothesize that 4 hours of TVNS will suppress inflammatory markers and improve the balance between sympathetic and parasympathetic arms of ANS as measured by HRV, resulting in improved Sequential Organ Failure Assessment Score (SOFA). The preliminary data generated from this pilot study will lay the foundation for a larger clinical trial.

Enrollment: 34 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Septic shock (meeting severe sepsis and having persistent systolic blood pressure <90mmHg despite adequate fluid resuscitation).

Exclusion criteria

• Unilateral or bilateral vagotomy
• History of myocardial infarction or stroke in the last 1 year
• Recurrent vasovagal syncope
• Sick sinus syndrome without pacemaker
• Bifascicular heart block
• 2nd or 3rd-degree heart block
• Hypotension due to autonomic dysfunction
• Pregnant women
• Prisoners and patients with suicidal ideation

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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34 participants in 2 patient groups

Active Treatment

Experimental group

Description:

Patients will receive a single 4-hour session of active transcutaneous vagus nerve stimulation.

Treatment:

Device: Low Level Transcutaneous Vagus Nerve Stimulation

Device: Low Level Transcutaneous Vagus Nerve Stimulation

Sham Control

Sham Comparator group

Description:

Patients will receive a single 4-hour session of sham transcutaneous vagus nerve stimulation.

Treatment:

Device: Low Level Transcutaneous Vagus Nerve Stimulation

Device: Low Level Transcutaneous Vagus Nerve Stimulation