Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis

NCT ID: NCT03992378

Last Updated: 2024-03-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 34 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-10
• Study Completion Date: 2025-12-31

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Active Treatment

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

Group Type: EXPERIMENTAL

Low Level Transcutaneous Vagus Nerve Stimulation

Intervention Type: DEVICE

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

Sham Control

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

Group Type: SHAM_COMPARATOR

Low Level Transcutaneous Vagus Nerve Stimulation

Intervention Type: DEVICE

Stimulation of the ear lobe delivered by Parasym device.

Interventions

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.

Intervention Type: DEVICE

Low Level Transcutaneous Vagus Nerve Stimulation

Stimulation of the ear lobe delivered by Parasym device.

Intervention Type: DEVICE

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Oklahoma City VA Medical Center

FED

Sponsor Role: collaborator

University of Oklahoma

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Houssein Youness, MD

Role: PRINCIPAL_INVESTIGATOR

University of Oklahoma

Zain Ul Abideen Asad, MD

Role: PRINCIPAL_INVESTIGATOR

University of Oklahoma

Locations

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Houssein Youness, MD

Role: CONTACT

Houssein-Youness@ouhsc.edu

405-271-6173

Zain Ul Abideen Asad, MD

Role: CONTACT

Zain-Asad@ouhsc.edu

405-271-5963

Facility Contacts

Houssein Youness, MD

Role: primary

Houssein-Youness@ouhsc.edu

405-271-6173

References

Goggins E, Inoue H, Okusa MD. Neuroimmune Control of Inflammation in Acute Kidney Injury and Multiorgan Dysfunction. J Am Soc Nephrol. 2025 Jul 7. doi: 10.1681/ASN.0000000813. Online ahead of print.

Reference Type: DERIVED

PMID: 40622772 (View on PubMed)

Other Identifiers

9227

Identifier Type: -

Identifier Source: org_study_id