Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis

Septic Shock Clinical Trial

— NERINASEPSIS  

Official title:

Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03992378
• Other study ID #: 9227
• Status: Recruiting
• Phase: N/A
• Start date: October 10, 2019
• Est. completion date: December 2025

Study information

• Verified date: March 2024
• Source: University of Oklahoma
• Contact: Houssein Youness, MD
• Phone: 405-271-6173
• Email: Houssein-Youness[@]ouhsc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 34
• Est. completion date: December 2025
• Est. primary completion date: June 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Inflammation
• Sepsis
• Septic Shock

Intervention

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.
• Low Level Transcutaneous Vagus Nerve Stimulation
Stimulation of the ear lobe delivered by Parasym device.

Locations

Country	Name	City	State
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma

Sponsors (2)

Lead Sponsor	Collaborator
University of Oklahoma	Oklahoma City VA Medical Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Inflammatory Cytokine Tumor Necrosis Factor Alpha	Serum inflammatory cytokine	Baseline to 4 hours and baseline to 24 hours post stimulation
Secondary	Change in Heart Rate Variability	Time domain and frequency domain measures of heart rate variability	Baseline to 4 hours post stimulation
Secondary	Change in Sequential Organ Failure Assessment Score	Sequential Organ Failure Assessment Score calculation	Baseline to 24 hours post stimulation