NCT03992378 · University of Oklahoma
Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis
(NERINASEPSIS)
What this study is 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%.
View original scientific description
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.
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.
Primary outcome measures
Change in Inflammatory Cytokine Tumor Necrosis Factor Alpha
Time frame: Baseline to 4 hours and baseline to 24 hours post stimulation
Serum inflammatory cytokine
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
Where
- Oklahoma City, Oklahoma
Collaborators
Oklahoma City VA Medical Center
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Apr 1, 2026 · Source of record for eligibility and locations