Restless Legs SyndrometVNS-PPNCT05007743
Effects of Transcutaneous Vagus Nerve Stimulation in Chronic Pain Patients and Healthy Controls
A study testing Transcutaneous vagus nerve stimulation in people with Restless Legs Syndrome and Chronic Pain, run by University Medical Center Goettingen at 1 site in Germany.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Restless Legs Syndrome, Chronic Pain
- What is being tested?
- Transcutaneous vagus nerve stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteGermany
- Study dates
- 21 Jul 2019to Aug 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male and female participants between 18 and 80 years old
- Written informed consent
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: 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.
Read the 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.
- Conditions
- Restless Legs Syndrome, Chronic Pain
- Being tested
- Transcutaneous vagus nerve stimulation
- Keywords
- RLS, vagus nerve stimulation
- Medical subject headings
- Restless Legs Syndrome, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcutaneous vagus nerve stimulationDevice
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)
| Study group | Role | What they receive |
|---|---|---|
| Stimulation of inner tragus | Active comparator | Comparing autonomic hemodynamic functions and immune responses pre- and post-stimulation of the vagus nerve Receives: Device: Transcutaneous vagus nerve stimulation |
| Stimulation of ear lobe | Sham comparator | Comparing autonomic hemodynamic functions and immune responses pre- and post-stimulation of the vagus nerve Receives: Device: Transcutaneous vagus nerve stimulation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: Two days
Spectral analysis of heart rate variability
The normalized high frequency component of the RR intervals (HF-HRV) is expressed as a percentage.
Measured: Two days
Spontaneous baroreceptor sensitivity
The average baroreceptor sensitivity in ms/mmHg.
Measured: Two days
Secondary outcomes (6)
Serum cytokine concentrations
Interleukin-6, interleukin-8, interleukin-1ß and tumor necrosis factor alpha in pg/ml.
Measured: 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.
Measured: 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.
Measured: Two days
Sudoscan
Measurement of electrochemical skin conductance
Measured: 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.
Measured: 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.
Measured: Two days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2021
- Study start21 Jul 2019
- Primary completionAug 2023 (estimated)
- Study completionAug 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Restless Legs SyndromeStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- 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 blind
- Who is masked
- Participant, Investigator
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Medical Center Goettingen
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Prof. Thomas Meyer, University Medical Center Goettingen
- Investigators
- Thomas Meyer, Prof., Principal investigator, University of GöttingenElisabeth Veiz, M.Sc., Principal investigator, University of GöttingenChristoph Herrmann-Lingen, Prof., Principal investigator, University of Göttingen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05007743
- Sponsor's protocol ID
- 27/7/18
- Acronym
- tVNS-PP
- Status last verified
- May 2023
- First submitted
- 15 Jul 2021
- Last updated
- 10 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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.
PubMed 35576915
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Trial of Effects of Transcutaneous Vagus Nerve Stimulation in Chronic Pain Patients and Healthy Controls
- ClinicalTrials.gov ID
- NCT05007743
- Acronym / sponsor ID
- tVNS-PP / 27/7/18
- Conditions
- Restless Legs Syndrome, Chronic Pain
- Keywords
- RLS, vagus nerve stimulation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University Medical Center GoettingenUniversity, hospital or other
- Study start
- 21 Jul 2019 (actual)
- Primary completion
- Aug 2023 (estimated)
- Study completion
- Aug 2023 (estimated)
- First posted
- 16 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- 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
| Arm | Type | Receives |
|---|---|---|
| Stimulation of inner tragus | Active comparator | Device: Transcutaneous vagus nerve stimulationComparing autonomic hemodynamic functions and immune responses pre- and post-stimulation of the vagus nerve |
| Stimulation of ear lobe | Sham comparator | Device: Transcutaneous vagus nerve stimulationComparing autonomic hemodynamic functions and immune responses pre- and post-stimulation of the vagus nerve |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Male and female participants between 18 and 80 years old
- Written informed consent
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcutaneous vagus nerve stimulationFrequency 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) | Device | Stimulation of ear lobe, Stimulation of inner tragus |
Primary outcome
International RLS Severity Scale
Time frame: Seven days
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
Time frame: Two days
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
Time frame: Two days
The normalized high frequency component of the RR intervals (HF-HRV) is expressed as a percentage.
Spontaneous baroreceptor sensitivity
Time frame: Two days
The average baroreceptor sensitivity in ms/mmHg.
6 secondary outcomes
Serum cytokine concentrations
Time frame: Two days
Hospital Anxiety and Depression scale
Time frame: Two days
Median nerve stimulation
Time frame: Two days
Sudoscan
Time frame: Two days
Brief Pain Inventory
Time frame: Two days
Short Form 12 (SF-12)
Time frame: Two days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Derived from this study: PubMed 35576915Veiz 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Thomas Meyer, Prof. principal investigator
University of Göttingen
Elisabeth Veiz, M.Sc. principal investigator
University of Göttingen
Christoph Herrmann-Lingen, Prof. principal investigator
University of Göttingen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcutaneous vagus nerve stimulation in people with Restless Legs Syndrome and Chronic Pain, run by University Medical Center Goettingen at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
International RLS Severity Scale (time frame: Seven days). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05007743, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 May 2023.