Effects of Transcutaneous Vagus Nerve Stimulation in Chronic Pain Patients and Healthy Controls

Study Overview
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Brief Summary
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The tVNS-PP trial investigates the effects of transcutaneous vagus nerve stimulation (tVNS) on autonomic functions, immune responses, and disease severity in chronic pain and restless legs syndrome (RLS) patients as compared to healthy controls.

Detailed Description
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A pilot study with healthy participants will investigate whether transcutaneous vagus nerve stimulation at the inner tragus reduces heart rate variability and lowers blood pressure without causing undesirable, severe side effects. In addition, changes in immune markers will be analyzed in blood samples before and after the interventions. Patients with primary restless legs syndrome will undergo a similar experimental protocol, except that transcutaneous vagus nerve stimulation will be performed daily. The aim is to determine whether stimulation reduces disease severity and chronic pain while improving quality of life.

Official Title
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Randomized Trial of Effects of Transcutaneous Vagus Nerve Stimulation in Chronic Pain Patients and Healthy Controls

Conditions
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Restless Legs Syndrome, Chronic Pain

Intervention / Treatment
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* Device: Transcutaneous vagus nerve stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Male and female participants between 18 and 80 years old Written informed consent Exclusion criteria: Age younger than 18 years or older than 80 years Participants with somatic or mental comorbidities, especially malignant tumor diseases, cardiac insufficiencies > NYHA II, severe depressive episodes, psychosis or dementia Pregnancy or breast feeding Addictions to alcohol, medications or drugs (except tobacco) An existing legal guardianship Participation in another scientific study within the previous eight weeks before enrollment Restless Legs Syndrome patients with one of the following secondary predispositions: iron deficiency, polyneuropathy, prolapsed disk, spinal stenosis or chronic obstructive pulmonary disease

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: A crossover design is used for the investigation of the healthy cohort and a parallel design will be used for the patient group
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stimulation of inner tragus<br>Comparing autonomic hemodynamic functions and immune responses pre- and post-stimulation of the vagus nerve | Device: Transcutaneous vagus nerve stimulation<br>* Frequency of 30 Hz, biphasic, rectangular pulses with a pulse width of 250 µs and an intensity of 20 mA. Device: Easy Tens+ device (body clock, London, UK)<br>|
| Sham Comparator: Stimulation of ear lobe<br>Comparing autonomic hemodynamic functions and immune responses pre- and post-stimulation of the vagus nerve | Device: Transcutaneous vagus nerve stimulation<br>* Frequency of 30 Hz, biphasic, rectangular pulses with a pulse width of 250 µs and an intensity of 20 mA. Device: Easy Tens+ device (body clock, London, UK)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| International RLS Severity Scale | Numeric score quantifying disease severity. This numeric rating scale ranges from 0 to 40 points. The higher the achieved score, the higher is the RLS disease severity. 0 points: no symptoms, 1-10 points: mild symptoms, 11-20 points: moderate symptoms, 21-30 points: severe symptoms, 31-40 points: extreme symptoms | Seven days | 
| Time domain analysis of heart rate variability | The standard deviation of the RR intervals (SDNN) and the root mean square of successive differences (RMSSD) in milliseconds. | Two days | 
| Spectral analysis of heart rate variability | The normalized high frequency component of the RR intervals (HF-HRV) is expressed as a percentage. | Two days | 
| Spontaneous baroreceptor sensitivity | The average baroreceptor sensitivity in ms/mmHg. | Two days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum cytokine concentrations | Interleukin-6, interleukin-8, interleukin-1ß and tumor necrosis factor alpha in pg/ml. | Two days | 
| Hospital Anxiety and Depression scale | This questionnaire has 14 items that evaluate depression and anxiety symptoms. Each item has four possible responses and is scored in a range from zero to three with higher scores representing more symptoms. | Two days | 
| Median nerve stimulation | Electrical nerve stimulation of the median nerve to assess its strength-duration time constant (SDTC) or chronaxie in milliseconds. The SDTC is a measure of axonal excitability and provides indirect information about the functionality of sodium ion channels. | Two days | 
| Sudoscan | Measurement of electrochemical skin conductance | Two days | 
| Brief Pain Inventory | This questionnaire assesses pain severity, location of pain, and impact on daily functions in the past 24 hours. Pain severity is scored on a numeric scale from zero to ten, with zero being no pain and ten being the worst possible pain. | Two days | 
| Short Form 12 (SF-12) | This questionnaire assesses the quality of life using 12 items. Each item is scaled on a range between zero and a maximum of six. Weighted sums are calculated and transformed into a population-standardized score ranging between zero and 100. The higher the score, the better is the respective life quality compared to the average population. | Two days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RLS, vagus nerve stimulation