Clinical trial NCT03992378: Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis
Official title: Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Septic Shock
Keywords: Sepsis
Lead sponsor: University of Oklahoma
Sponsor class: OTHER
Collaborators: name: Oklahoma City VA Medical Center
First posted: 2019-06-20
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized controlled trial
Primary purpose: TREATMENT

Brief 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.


Eligibility criteria: 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

Primary outcomes:
measure: Change in Inflammatory Cytokine Tumor Necrosis Factor Alpha
timeFrame: Baseline to 4 hours and baseline to 24 hours post stimulation
Secondary outcomes:
measure: Change in Heart Rate Variability
timeFrame: Baseline to 4 hours post stimulation
measure: Change in Sequential Organ Failure Assessment Score
timeFrame: Baseline to 24 hours post stimulation
Other outcomes:
Locations:
city: Oklahoma City
country: United States
facility: University of Oklahoma Health Sciences Center
state: Oklahoma
Study officials:
affiliation: University of Oklahoma
name: Houssein Youness, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Oklahoma
name: Zain Ul Abideen Asad, MD
role: PRINCIPAL_INVESTIGATOR
References: