Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis

NCT03992378 | Recruiting DMC FDA Device

• 1 other identifier: 9227
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

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.

Conditions

Septic Shock

Keywords

Sepsis

Outcome Measures

Primary Outcomes (1)

• Change in Inflammatory Cytokine Tumor Necrosis Factor Alpha

  Serum inflammatory cytokine

  Baseline to 4 hours and baseline to 24 hours post stimulation

Secondary Outcomes (2)

• Change in Heart Rate Variability

  Baseline to 4 hours post stimulation

• Change in Sequential Organ Failure Assessment Score

  Baseline to 24 hours post stimulation

Study Arms (2)

Active Treatment

EXPERIMENTAL

Patients will receive a single 4-hour session of active transcutaneous vagus nerve stimulation.

Device: Low Level Transcutaneous Vagus Nerve Stimulation

Sham Control

SHAM COMPARATOR

Patients will receive a single 4-hour session of sham transcutaneous vagus nerve stimulation.

Device: Low Level Transcutaneous Vagus Nerve Stimulation

Interventions

Low Level Transcutaneous Vagus Nerve Stimulation DEVICE

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

Active Treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Septic shock (meeting severe sepsis and having persistent systolic blood pressure \<90mmHg despite adequate fluid resuscitation).

You may not qualify if:

• 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
• nd or 3rd-degree heart block
• Hypotension due to autonomic dysfunction
• Pregnant women
• Prisoners and patients with suicidal ideation

Sponsors & Collaborators

• University of Oklahoma: lead
• Oklahoma City VA Medical Center: collaborator

Study Sites (1)

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

Related Publications (1)

• Goggins E, Inoue H, Okusa MD. Neuroimmune Control of Inflammation in Acute Kidney Injury and Multiorgan Dysfunction. J Am Soc Nephrol. 2025 Dec 1;36(12):2473-2484. doi: 10.1681/ASN.0000000813. Epub 2025 Jul 7.

  PMID: 40622772 DERIVED

MeSH Terms

Conditions

Shock, Septic; Sepsis

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Study Officials

• Houssein Youness, MD

  University of Oklahoma

  PRINCIPAL INVESTIGATOR

• Zain Ul Abideen Asad, MD

  University of Oklahoma

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Houssein Youness, MD

CONTACT

405-271-6173; Houssein-Youness@ouhsc.edu

Zain Ul Abideen Asad, MD

CONTACT

405-271-5963; Zain-Asad@ouhsc.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: Double blind
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized controlled trial

Study Record Dates

• First Submitted: June 5, 2019
• First Posted: June 20, 2019
• Study Start: October 10, 2019
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 1, 2026

Record last verified: 2026-03

Locations

US (1)