4006-776-356 出国就医服务电话

免费获得国外相关药品，最快 1 个工作日回馈药物信息

出境医 / 临床实验 / Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis (NERINA-SEPSIS)

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

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 Not Applicable

Study Design
Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized 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
Estimated Study Start Date : November 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 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 [ Time Frame: Baseline to 4 hours and baseline to 24 hours post stimulation ]
    Serum inflammatory cytokine


Secondary Outcome Measures :
  1. Change in Heart Rate Variability [ Time Frame: Baseline to 4 hours post stimulation ]
    Time domain and frequency domain measures of heart rate variability

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


Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations

Contacts
Layout table for location contacts
Contact: Houssein Youness, MD 405-271-6173 Houssein-Youness@ouhsc.edu
Contact: Zain Ul Abideen Asad, MD 405-271-5963 Zain-Asad@ouhsc.edu

Locations
Layout table for location information
United States, Oklahoma
University of Oklahoma Health Sciences Center Recruiting
Oklahoma City, Oklahoma, United States, 73104
Contact: Lauren Sinko, RN    405-271-6173    Lauren-A-Sinko@ouhsc.edu   
Contact: Kassidy Malone, RN    4052716173    Kassidy-Malone@ouhsc.edu   
Sponsors and Collaborators
University of Oklahoma
Oklahoma City VA Medical Center
Investigators
Layout table for investigator information
Principal Investigator: Houssein Youness, MD University of Oklahoma
Principal Investigator: Zain Ul Abideen Asad, MD University of Oklahoma
Tracking Information
First Submitted Date  ICMJE June 5, 2019
First Posted Date  ICMJE June 20, 2019
Last Update Posted Date October 19, 2020
Estimated Study Start Date  ICMJE November 2020
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 18, 2019) 		Change in Inflammatory Cytokine Tumor Necrosis Factor Alpha [ Time Frame: Baseline to 4 hours and baseline to 24 hours post stimulation ]
Serum inflammatory cytokine
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 18, 2019)
  • Change in Heart Rate Variability [ Time Frame: Baseline to 4 hours post stimulation ]
    Time domain and frequency domain measures of heart rate variability
  • Change in Sequential Organ Failure Assessment Score [ Time Frame: Baseline to 24 hours post stimulation ]
    Sequential Organ Failure Assessment Score calculation
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis
Official Title  ICMJE Neuromodulation to Regulate Inflammation and Autonomic Imbalance in Sepsis
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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Randomized controlled trial
Masking: Double (Participant, Outcomes Assessor)
Masking Description:
Double blind
Primary Purpose: Treatment
Condition  ICMJE Septic Shock
Intervention  ICMJE
  • 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.
  • Device: Low Level Transcutaneous Vagus Nerve Stimulation
    Stimulation of the ear lobe delivered by Parasym device.
Study Arms  ICMJE
  • Experimental: Active Treatment
    Patients will receive a single 4-hour session of active transcutaneous vagus nerve stimulation.
    Intervention: Device: Low Level Transcutaneous Vagus Nerve Stimulation
  • Sham Comparator: Sham Control
    Patients will receive a single 4-hour session of sham transcutaneous vagus nerve stimulation.
    Intervention: Device: Low Level Transcutaneous Vagus Nerve Stimulation
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 18, 2019) 		34
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2024
Estimated Primary Completion Date June 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Houssein Youness, MD 405-271-6173 Houssein-Youness@ouhsc.edu
Contact: Zain Ul Abideen Asad, MD 405-271-5963 Zain-Asad@ouhsc.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03992378
Other Study ID Numbers  ICMJE 9227
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Oklahoma
Study Sponsor  ICMJE University of Oklahoma
Collaborators  ICMJE Oklahoma City VA Medical Center
Investigators  ICMJE
Principal Investigator: Houssein Youness, MD University of Oklahoma
Principal Investigator: Zain Ul Abideen Asad, MD University of Oklahoma
PRS Account University of Oklahoma
Verification Date October 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP

治疗医院

新药特效药

前沿医讯