Back to resultsEffects of Transcutaneous Vagus Nerve Stimulation in Chronic Pain Patients and Healthy Controls (tVNS-PP)
Primary Purpose
Restless Legs Syndrome, Chronic Pain
Status
Active
Phase
Not Applicable
Locations
Germany
Study Type
Interventional
Intervention
Transcutaneous vagus nerve stimulation
Sponsored by
About this trial
This is an interventional basic science trial for Restless Legs Syndrome focused on measuring RLS, vagus nerve stimulation
Eligibility Criteria
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
Sites / Locations
- University Medical Center
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Sham Comparator
Arm Label
Stimulation of inner tragus
Stimulation of ear lobe
Arm Description
Comparing autonomic hemodynamic functions and immune responses pre- and post-stimulation of the vagus nerve
Comparing autonomic hemodynamic functions and immune responses pre- and post-stimulation of the vagus nerve
Outcomes
Primary Outcome Measures
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
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.
Spectral analysis of heart rate variability
The normalized high frequency component of the RR intervals (HF-HRV) is expressed as a percentage.
Spontaneous baroreceptor sensitivity
The average baroreceptor sensitivity in ms/mmHg.
Secondary Outcome Measures
Serum cytokine concentrations
Interleukin-6, interleukin-8, interleukin-1ß and tumor necrosis factor alpha in pg/ml.
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.
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.
Sudoscan
Measurement of electrochemical skin conductance
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.
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.
Full Information
NCT ID
NCT05007743
First Posted
July 15, 2021
Last Updated
May 9, 2023
Sponsor
University Medical Center Goettingen
1. Study Identification
Unique Protocol Identification Number
NCT05007743
Brief Title
Effects of Transcutaneous Vagus Nerve Stimulation in Chronic Pain Patients and Healthy Controls
Acronym
tVNS-PP
Official Title
Randomized Trial of Effects of Transcutaneous Vagus Nerve Stimulation in Chronic Pain Patients and Healthy Controls
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 21, 2019 (Actual)
Primary Completion Date
August 2023 (Anticipated)
Study Completion Date
August 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Goettingen
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Restless Legs Syndrome, Chronic Pain
Keywords
RLS, vagus nerve stimulation
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
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
ParticipantInvestigator
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Stimulation of inner tragus
Arm Type
Active Comparator
Arm Description
Comparing autonomic hemodynamic functions and immune responses pre- and post-stimulation of the vagus nerve
Arm Title
Stimulation of ear lobe
Arm Type
Sham Comparator
Arm Description
Comparing autonomic hemodynamic functions and immune responses pre- and post-stimulation of the vagus nerve
Intervention Type
Device
Intervention Name(s)
Transcutaneous vagus nerve stimulation
Intervention Description
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)
Primary Outcome Measure Information:
Title
International RLS Severity Scale
Description
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
Time Frame
Seven days
Title
Time domain analysis of heart rate variability
Description
The standard deviation of the RR intervals (SDNN) and the root mean square of successive differences (RMSSD) in milliseconds.
Time Frame
Two days
Title
Spectral analysis of heart rate variability
Description
The normalized high frequency component of the RR intervals (HF-HRV) is expressed as a percentage.
Time Frame
Two days
Title
Spontaneous baroreceptor sensitivity
Description
The average baroreceptor sensitivity in ms/mmHg.
Time Frame
Two days
Secondary Outcome Measure Information:
Title
Serum cytokine concentrations
Description
Interleukin-6, interleukin-8, interleukin-1ß and tumor necrosis factor alpha in pg/ml.
Time Frame
Two days
Title
Hospital Anxiety and Depression scale
Description
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.
Time Frame
Two days
Title
Median nerve stimulation
Description
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.
Time Frame
Two days
Title
Sudoscan
Description
Measurement of electrochemical skin conductance
Time Frame
Two days
Title
Brief Pain Inventory
Description
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.
Time Frame
Two days
Title
Short Form 12 (SF-12)
Description
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.
Time Frame
Two days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Thomas Meyer, Prof.
Organizational Affiliation
University of Göttingen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Elisabeth Veiz, M.Sc.
Organizational Affiliation
University of Göttingen
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Christoph Herrmann-Lingen, Prof.
Organizational Affiliation
University of Göttingen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Center
City
Göttingen
ZIP/Postal Code
37073
Country
Germany
12. IPD Sharing Statement
Citations:
PubMed Identifier
35576915
Citation
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.
Results Reference
derived
Learn more about this trial
Effects of Transcutaneous Vagus Nerve Stimulation in Chronic Pain Patients and Healthy Controls
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