Pilot Study - Auricular Vagus Nerve Stimulation Effects on Cardiovascular Parameters

• ClinicalTrials.gov Identifier: NCT02139293
• Recruitment Status: Unknown
• First Posted: May 15, 2014
• Last Update Posted: September 5, 2017
• Sponsor: Medical University of Vienna
• Collaborator: Vienna University of Technology
• Information provided by (Responsible Party): Dr. Jozsef Constantin Széles, Medical University of Vienna

Tracking Information

• First Submitted Date: May 13, 2014
• First Posted Date: May 15, 2014
• Last Update Posted Date: September 5, 2017
• Estimated Study Start Date: January 2018
• Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 15, 2014)

• change in heart rate variability (HRV) related to stimulation site in the auricle [ Time Frame: within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles ]
  Heart rate variability will be assessed as, e.g., standard deviation in heart rate over a time window of 5 minutes (2.5 minutes overlap), total power or low to high frequency power. Changes in assessed heart rate variability parameters will be assessed and compared between subjects with respect to stimulation site using statistical tests.
• change in local blood perfusion index (BPI) related to stimulation site in the auricle [ Time Frame: within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles ]
  Blood perfusion index at the foot will be assessed as peak-peak amplitude (systolic to diastolic) divided by the mean signal value of optically measured blood perfusion. Changes in mean value and standard deviation of local blood perfusion index will be assessed and compared between subjects with respect to stimulation site using statistical tests.

Original Primary Outcome Measures (submitted: May 13, 2014)

• change in heart rate variability (HRV) related to stimulation site in the auricle [ Time Frame: within 4 days of intervention ]
  Heart rate variability will be assessed as, e.g., standard deviation in heart rate over a time window of 5 minutes (2.5 minutes overlap), total power or low to high frequency power. Changes in assessed heart rate variability parameters will be assessed and compared between subjects with respect to stimulation site using statistical tests.
• change in local blood perfusion index (BPI) related to stimulation site in the auricle [ Time Frame: within 4 days of intervention ]
  Blood perfusion index at the foot will be assessed as peak-peak amplitude (systolic to diastolic) divided by the mean signal value of optically measured blood perfusion. Changes in mean value and standard deviation of local blood perfusion index will be assessed and compared between subjects with respect to stimulation site using statistical tests.

Current Secondary Outcome Measures (submitted: May 15, 2014)

• Change of local BPI in upper and lower extremities [ Time Frame: within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles ]
  Local BPI is assessed using optical sensors on the foot and the finger of participants. Changes in mean value of BPI are analyzed using statistical tests.
• Changes in blood pressure [ Time Frame: within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles ]
  Blood pressure is continuously measured using inflatable finger cuffs.
• Changes in respiratory activity [ Time Frame: within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles ]
  Respiratory activity is monitored using a respiratory belt.
• Changes in oxygen saturation of the toe [ Time Frame: within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles ]
• Changes in partial transcutaneous oxygen pressure of the forefoot [ Time Frame: within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles ]
• Changes in foot skin temperature [ Time Frame: within 4 days of intervention, at each day of intervention from baseline to stimulation and pause cycles ]
• Changes of C reactive protein- and leukocyte-concentration in serum [ Time Frame: at screening and at the last day of intervention ]
• Tolerance of stimulation [ Time Frame: at each day of intervention at the stimulation cycles ]
  Tolerance of stimulation is assessed by free survey.
• Perception of Stimulation [ Time Frame: at each day of intervention at the stiumulation cycles ]
  Perception of stimulation is assessed by free survey.
• Adverse effects of stimulation [ Time Frame: within 4 days of intervention ]

Original Secondary Outcome Measures (submitted: May 13, 2014)

• Change of local BPI in upper and lower extremities [ Time Frame: within 4 days of intervention ]
  Local BPI is assessed using optical sensors on the foot and the finger of participants. Changes in mean value of BPI are analyzed using statistical tests.
• Changes in blood pressure [ Time Frame: within 4 days of intervention ]
  Blood pressure is continuously measured using inflatable finger cuffs.
• Changes in respiratory activity [ Time Frame: within 4 days of intervention ]
  Respiratory activity is monitored using a respiratory belt.
• Changes in oxygen saturation of the toe [ Time Frame: within 4 days of intervention ]
• Changes in partial transcutaneous oxygen pressure of the forefoot [ Time Frame: within 4 days of intervention ]
• Changes in foot skin temperature [ Time Frame: within 4 days of intervention ]
• Changes of C reactive protein- and leukocyte-concentration in serum [ Time Frame: within 4 days of intervention ]
• Tolerance of stimulation [ Time Frame: within 4 days of intervention ]
  Tolerance of stimulation is assessed by free survey.
• Perception of Stimulation [ Time Frame: within 4 days of intervention ]
  Perception of stimulation is assessed by free survey.
• Adverse effects of stimulation [ Time Frame: within 4 days of intervention ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Pilot Study - Auricular Vagus Nerve Stimulation Effects on Cardiovascular Parameters
• Official Title: Functional Mapping of Auricular Vagal Stimulation Points on Cardiovascular Parameters in Healthy Subjects - Pilot Study
• Brief Summary: The purpose of this pilot study is to evaluate the effect of auricular autonomous nervous system stimulation on cardiovascular parameters and sympathovagal balance in healthy subjects. It is investigated if auricular vagal nerve stimulation affects heart rate variability as well as peripheral local blood perfusion, and if this effect depends on the site of stimulation in the auricle, whereas four distinct stimulation points are tested.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Basic Science
• Condition: Modulation of Cardiovascular Parameters and Sympathovagal Balance in Healthy Subjects

Intervention

Device: PrimeStim

Intermittent auricular vagus nerve stimulation at different ear points

Study Arms

Experimental: auricular vagus nerve stimulation

Study participants (healthy) are treated with auricular vagus nerve stimulation using five needle electrodes connected to an electrical stimulation device (PrimeStim). After acclimatization the stimulation is turned on for 20 minutes followed by 20 minutes of paused stimulation, 20 minutes of stimulation, and 10 minutes paused stimulation. This intervention is repeated on four consecutive days, whereas at each intervention only one of the four stimulation points (and one fixed reference point) is stimulated. Needle electrodes are applied at each study visit.

Stimulation points in the auricle are stimulated in random order. One stimulation pattern is tested. Stimulation amplitudes are adjusted with respect to a distinct but comfortable sensation at the auricle.

During the described protocol various biosignals are continuously recorded, including ECG, respiration, blood perfusion, oxygen saturation, transcutaneous oxygen tension, blood pressure and skin temperature.

Intervention: Device: PrimeStim

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: May 13, 2014): 10
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2018
• Estimated Primary Completion Date: December 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• men and women aged 20 to 50 years

Exclusion Criteria:

• participation in a clinical trial in the last 5 weeks
• diseases which may affect the autonomous nervous system (e.g., diabetes mellitus)
• confounding medical treatment with known effects on the autonomous nervous system (e.g., beta blocker)
• drug abuse
• active implanted devices
• pregnancy or nursing

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years to 50 Years (Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Austria

Administrative Information

• NCT Number: NCT02139293
• Other Study ID Numbers: PS 02/2014
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Responsible Party: Dr. Jozsef Constantin Széles, Medical University of Vienna
• Study Sponsor: Medical University of Vienna
• Collaborators: Vienna University of Technology

Investigators

• Principal Investigator: Jozsef C Széles, Dr.med.; University Clinic for Surgery, Department of Transplantation, Medical University Vienna

• PRS Account: Medical University of Vienna
• Verification Date: September 2017