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

Study Overview
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Brief Summary
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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).

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

Conditions
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Chronic Diabetic Foot Ulcers

Intervention / Treatment
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* Device: PrimeStim


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: auricular vagal nerve stimulation<br>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<br> <br> |

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Adverse effects of stimulation |  | within 4 days of intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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vagus nerve stimulation effects on heart rate variability and peripheral blood perfusion