Effects of Transcutaneous Vagus Nerve Stimulation in Chronic Pain Patients and Healthy Controls (tVNS-PP)

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Chronic Pain; Restless Legs Syndrome
• Intervention / Treatment: Device: Transcutaneous vagus nerve stimulation

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Thomas Meyer, Prof.; Phone Number: +495513964940; Email: thomas.meyer@med.uni-goettingen.de
• Study Contact Backup: Name: Dirk Czesnik, PD Dr.; Email: dczesni@gwdg.de

Study Locations

• Germany
  • Göttingen, Germany, 37073
    • University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Stimulation of inner tragus; Comparing autonomic hemodynamic functions and immune responses pre- and post-stimulation of the vagus nerve	Device: Transcutaneous vagus nerve stimulation; 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)
Sham Comparator: Stimulation of ear lobe; Comparing autonomic hemodynamic functions and immune responses pre- and post-stimulation of the vagus nerve	Device: Transcutaneous vagus nerve stimulation; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Medical Center Goettingen
• Investigators: Principal Investigator: Thomas Meyer, Prof., University of Göttingen; Principal Investigator: Elisabeth Veiz, M.Sc., University of Göttingen; Principal Investigator: Christoph Herrmann-Lingen, Prof., University of Göttingen

Publications and helpful links

General Publications

• Veiz E, Kieslich SK, Czesnik D, Herrmann-Lingen C, Meyer T, Staab J. Increased Concentrations of Circulating Interleukins following Non-Invasive Vagus Nerve Stimulation: Results from a Randomized, Sham-Controlled, Crossover Study in Healthy Subjects. Neuroimmunomodulation. 2022;29(4):450-459. doi: 10.1159/000524646. Epub 2022 May 16.

Study record dates

Study Major Dates

• Study Start (Actual): July 21, 2019
• Primary Completion (Anticipated): August 1, 2023
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: July 15, 2021
• First Submitted That Met QC Criteria: August 9, 2021
• First Posted (Actual): August 16, 2021

Study Record Updates

• Last Update Posted (Actual): May 10, 2023
• Last Update Submitted That Met QC Criteria: May 9, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: RLS, vagus nerve stimulation
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Pain; Neurologic Manifestations; Parasomnias; Chronic Pain; Restless Legs Syndrome
• Other Study ID Numbers: 27/7/18

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No