NERINA-SEPSIS: Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis

• Sponsor: University of Oklahoma (Other)
• Overall Status: Recruiting
• CT.gov ID: NCT03992378
• Collaborator: Oklahoma City VA Medical Center (U.S. Fed)
• Enrollment: 34
• Location: 1
• Arms: 2
• Anticipated Duration (Months): 43
• Patients Per Site Per Month: 0.8

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Septic Shock	Device: Low Level Transcutaneous Vagus Nerve Stimulation; Device: Low Level Transcutaneous Vagus Nerve Stimulation	N/A

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 34 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Randomized controlled trialRandomized controlled trial
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: Double blind
• Primary Purpose: Treatment
• Official Title: Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis
• Anticipated Study Start Date: Nov 1, 2020
• Anticipated Primary Completion Date: Jun 1, 2022
• Anticipated Study Completion Date: Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Treatment Patients will receive a single 4-hour session of active transcutaneous vagus nerve stimulation.	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.
Sham Comparator: Sham Control Patients will receive a single 4-hour session of sham transcutaneous vagus nerve stimulation.	Device: Low Level Transcutaneous Vagus Nerve Stimulation; Stimulation of the ear lobe delivered by Parasym device.

Outcome Measures

Primary Outcome Measures

1. Change in Inflammatory Cytokine Tumor Necrosis Factor Alpha [Baseline to 4 hours and baseline to 24 hours post stimulation]

   Serum inflammatory cytokine

Secondary Outcome Measures

1. Change in Heart Rate Variability [Baseline to 4 hours post stimulation]

   Time domain and frequency domain measures of heart rate variability

2. Change in Sequential Organ Failure Assessment Score [Baseline to 24 hours post stimulation]

   Sequential Organ Failure Assessment Score calculation

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma	United States	73104

Sponsors and Collaborators

• University of Oklahoma
• Oklahoma City VA Medical Center

Investigators

• Principal Investigator: Houssein Youness, MD, University of Oklahoma
• Principal Investigator: Zain Ul Abideen Asad, MD, University of Oklahoma

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Oklahoma
• ClinicalTrials.gov Identifier: NCT03992378
• Other Study ID Numbers: 9227
• First Posted: Jun 20, 2019
• Last Update Posted: Oct 19, 2020
• Last Verified: Oct 1, 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Product Manufactured in and Exported from the U.S.: Yes
• Keywords provided by University of Oklahoma: Sepsis
• Additional relevant MeSH terms: Sepsis; Inflammation

Study Results

No Results Posted as of Oct 19, 2020