Pilot Study on Auricular Vagus Nerve Stimulation Effects in Chronic Diabetic Wounds

Evaluation of Electrical Auricular Vagal Nerve Stimulation Effects on Parameters of Wound Healing in Chronic Diabetic Wounds - Pilot Study

The purpose of this pilot study is to evaluate the effect of auricular autonomous nervous system stimulation on vital parameters of wound healing in diabetics. It is investigated if auricular vagal nerve stimulation has an effect on heart rate variability as well as peripheral local blood perfusion, and if this effect depends on the health status of the study participants (diseased/healthy).

Study Overview

• Status: Completed
• Conditions: Chronic Diabetic Foot Ulcers
• Intervention / Treatment: Device: PrimeStim

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria, 1090
    • University Clinic for Surgery, Department of Transplantation, Medical University Vienna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diabetes mellitus type 2
• ulcus cruris (plantar)
• min. 6 weeks of standard wound therapy without success
• intact big toe on wound side

Exclusion Criteria:

• participation in a clinical trial in the last 5 weeks
• confounding medical treatment, e.g. prostaglandin
• vascular diseases other than peripheral arterial occlusive disease
• diseases which may affect the autonomous nervous system or wound healing, except diabetic concomitant diseases (e.g., polyneuropathy, angiopathy)
• drug abuse
• active implanted devices
• pregnancy or nursing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: auricular vagal nerve stimulation; Study participants (healthy and diabetics) are treated with auricular vagal nerve stimulation using four needle electrodes connected to an electrical stimulation device (PrimeStim). After an acclimatization phase the stimulation is turned on for 20 minutes followed by 20 minutes of paused stimulation, 20 minutes of stimulation, and another 10 minutes paused stimulation. This intervention is repeated on four consecutive days. Needle electrodes stay fixed over the whole study period. Two different stimulation schemes are tested, each being assessed twice in random order. 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.

Device: PrimeStim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in heart rate variability (HRV) related to physiological state (diabetics/healthy)	Heart rate variability will be assessed as, e.g., standard deviation in heart rate over a time window of 5 minutes (30 seconds overlap). Changes in mean value and standard deviation of heart rate variability between healthy and diabetic patients will be assessed using statistical tests.	within 4 days of intervention
change in local blood perfusion index (BPI) related to physiological state (diabetics/healthy)	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 between healthy and diabetic patients will be assessed using statistical tests.	within 4 days of intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse effects of stimulation		within 4 days of intervention
Change in HRV and local BPI due to distinct stimulation patterns	Two distinct stimulation patterns are tested during intervention. Changes in mean value and standard deviation of HRV/BPI due to these stimulation patterns will be assessed using statistical tests.	within 4 days of intervention
Change of local BPI in upper and lower extremities	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.	within 4 days of intervention
Changes in blood pressure	Blood pressure is continuously measured using inflatable finger cuffs.	within 4 days of intervention
Changes in respiratory activity	Respiratory activity is monitored using a respiratory belt.	within 4 days of intervention
Changes in oxygen saturation of the toe and wound		within 4 days of intervention
Changes in partial transcutaneous oxygen pressure of the wound region		within 4 days of intervention
Changes in foot skin temperature		within 4 days of intervention
Changes of C reactive protein- and leukocyte-concentration in serum		within 4 days of intervention
Tolerance of stimulation	Tolerance of stimulation is assessed by survey.	within 4 days of intervention
Perception of Stimulation	Perception of stimulation is assessed by survey.	within 4 days of intervention

Collaborators and Investigators

• 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

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (Actual): April 13, 2015
• Study Completion (Actual): April 13, 2015

Study Registration Dates

• First Submitted: March 20, 2014
• First Submitted That Met QC Criteria: March 27, 2014
• First Posted (Estimate): March 28, 2014

Study Record Updates

• Last Update Posted (Actual): March 31, 2017
• Last Update Submitted That Met QC Criteria: March 30, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: vagus nerve stimulation effects on heart rate variability and peripheral blood perfusion
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Endocrine System Diseases; Diabetic Angiopathies; Leg Ulcer; Skin Ulcer; Diabetes Complications; Diabetes Mellitus; Diabetic Neuropathies; Foot Diseases; Diabetic Foot; Foot Ulcer
• Other Study ID Numbers: PS 01/2014