Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis

Summary

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.

Conditions

• Septic Shock

Interventions

DEVICE

Low Level Transcutaneous Vagus Nerve Stimulation

Stimulation of the auricular branch of the vagus nerve at tragus of the external ear delivered by Parasym device.

DEVICE

Low Level Transcutaneous Vagus Nerve Stimulation

Stimulation of the ear lobe delivered by Parasym device.

Sponsors & Collaborators

• Oklahoma City VA Medical Center

  collaborator FED

• University of Oklahoma

  lead OTHER

Principal Investigators

• Houssein Youness, MD · University of Oklahoma

• Zain Ul Abideen Asad, MD · University of Oklahoma

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-10-10

Primary Completion

2027-06-30

Completion

2027-12-31

FDA Device

Yes

Countries

• United States

Study Locations