EpilepsyNCT05639387
TMS as a Tool for the Evaluation of Neuromodulatory Effects of Transcutaneous Vagus Nerve Stimulation
A study testing actual tVNS in people with Epilepsy, run by University Ghent at 1 site in Belgium.
Trial summary
Transcutaneous vagus nerve stimulation (tVNS) has been investigated as a potential treatment for epilepsy with inconsistent results. The combination of transcranial magnetic stimulation with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) allows to investigate the neuromodulatory effect of… Read more about this study
- Who is it for?
- Ages 18 to 65 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Epilepsy
- What is being tested?
- actual tVNS
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 15 participants
- Where
- 1 siteBelgium
- Study dates
- 6 Feb 2019to 1 Sep 2019
- 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 65 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- estimated IQ > 70
- healthy volunteer, taken from anamensis, clinical neurological examination and clinical estimation of researcher
- no history of central neurological condition
- no treatment with neurotropic drugs
- TMS safety screening questionnaire
- ICF signed
Who cannot join
- intracranial metal objects/materials (excl teeth fillings): vascular clips, shrapnell electrodes below stimulation area
- pacemaker, implanted defibrillator, permanent medication pump, cochlear implant or deep brain stimulation (DBS)
Trial locations and contacts
1 site in 1 country.
About this study
Transcutaneous vagus nerve stimulation (tVNS) has been investigated as a potential treatment for epilepsy with inconsistent results. The combination of transcranial magnetic stimulation with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) allows to investigate the neuromodulatory effect of interventions such as tVNS by evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs). The goal of this study is to objectively evaluate the effect of tVNS on cortical excitability with TMS-EMG and TMS-EEG. These findings are expected to provide insight in the mechanism of action and help identify more optimal stimulation paradigms.
In this prospective single-blind cross-over study, 15 healthy subjects will undergo active and sham tVNS during 60 minutes, using a maximum tolerated stimulation current. Single and paired pulse TMS will be delivered over the right-sided motor hotspot to evaluate MEPs and TEPs before and after the intervention.
Read the detailed description
In the past two decades, vagus nerve stimulation (VNS)has become a valuable treatment option for patients with refractory epilepsy. However, VNS requires a surgical procedure associated with potential side effects. Therefore, the development of non-invasive devices that selectively target the vagus nerve fibers with a low risk profile has gained interest. Transcutaneous auricular VNS (tVNS) is such a non-invasive neurostimulation modality that targets the cutaneous receptive field of the auricular branch of the vagus nerve located in the outer ear. Up to date, tVNS has been investigated as a potential treatment for epilepsy with inconsistent results. The goal of this study is to investigate the effect of tVNS on cortical excitability. This will provide important insight into the underlying effects of this technique on brain neurophysiology. Cortical excitability will be investigated by combining transcranial magnetic stimulation with electromyography (TMS-EMG) and electroencephalography (TMS-EEG), evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs).
In this prospective, single-blind, cross-over study, we will include 15 healthy male participants. They will undergo a TMS safety screening (TSS) questionnaire and clinical neurological examination before inclusion. Each participant will complete 2 sessions at least one week apart, one with active tVNS and one with sham tVNS.
The intervention is tVNS by means of the Nemos® device which stimulates the cymba conchae at the outer ear. Stimulation parameters are set to a frequency of 25 Hz, a pulsewidth of 250 µs, 7 s ON, 18 s OFF. The output current is ramped up until the user feels a tingling sensation at the stimulation site, but should remain subthreshold to painful stimulation. Stimulation is delivered during 60 min.Sham stimulation is achieved by placing the electrode on the earlobe instead of the cymba conchae.
Before and after the intervention 120 single TMS pulses, 120 paired pulses with an interstimulus interval of 3ms and 120 paired pulses with an interstimulus interval of 100ms will be delivered over the right motor hotspot. MEPs will be measured at the left first dorsal interosseus muscle. TEPs will be measured using a 64-channel TMS-compatible electrode cap. MEPS and TEPS will be preprocessed offline in Matlab. TEP and MEP morphology ( amplitude and latency) will be evaluated before and after the intervention to investigate changes in cortical excitability.
- Conditions
- Epilepsy
- Being tested
- actual tVNS, sham tVNS
- Medical subject headings
- Epilepsy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
actual tVNSProcedure or surgery
Active tVNS (stimulation on cymba conchae --> nervus vagus stimulation)
sham tVNSProcedure or surgery
Sham tVNS (stimulation on earlobe --> no nervus vagus stimulation)
| Study group | Role | What they receive |
|---|---|---|
| Group of healthy volunteers (part I) | Experimental | Participants will undergo active tVNS. Receives: Procedure: actual tVNS |
| Group of healthy volunteers (part II) | Sham comparator | Participants will undergo sham tVNS. Receives: Procedure: sham tVNS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measuring the electric activity of the brain evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs) during transcutaneous nervus vagus stimulation.
Using transcranial magnetic stimulation (TMS), the influence of the tVNS is measured.
Measured: 60 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Dec 2022
- Study start6 Feb 2019
- Primary completion19 Aug 2019
- Study completion1 Sep 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for EpilepsyStudies of the same condition, open and under way.
- More trials run by University GhentThe sponsor's other registered studies.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Each participant will complete 2 sessions at least one week apart, one with active tVNS and one with sham tVNS.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Ghent
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul Boon, MD, PhD, Principal investigator, University Hospital, Ghent
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05639387
- Sponsor's protocol ID
- 2018/0988
- Status last verified
- Dec 2022
- First submitted
- 9 Nov 2022
- Last updated
- 6 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- TMS as a Tool for the Evaluation of Neuromodulatory Effects of Transcutaneous Vagus Nerve Stimulation
- ClinicalTrials.gov ID
- NCT05639387
- Acronym / sponsor ID
- 2018/0988
- Conditions
- Epilepsy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- University GhentUniversity, hospital or other
- Study start
- 6 Feb 2019 (actual)
- Primary completion
- 19 Aug 2019 (actual)
- Study completion
- 1 Sep 2019 (actual)
- First posted
- 6 Dec 2022 (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.
Transcutaneous vagus nerve stimulation (tVNS) has been investigated as a potential treatment for epilepsy with inconsistent results. The combination of transcranial magnetic stimulation with electromyography (TMS-EMG) and electroencephalography (TMS-EEG) allows to investigate the neuromodulatory effect of interventions such as tVNS by evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs). The goal of this study is to objectively evaluate the effect of tVNS on cortical excitability with TMS-EMG and TMS-EEG. These findings are expected to provide insight in the mechanism of action and help identify more optimal stimulation paradigms.
In this prospective single-blind cross-over study, 15 healthy subjects will undergo active and sham tVNS during 60 minutes, using a maximum tolerated stimulation current. Single and paired pulse TMS will be delivered over the right-sided motor hotspot to evaluate MEPs and TEPs before and after the intervention.
Detailed description
In the past two decades, vagus nerve stimulation (VNS)has become a valuable treatment option for patients with refractory epilepsy. However, VNS requires a surgical procedure associated with potential side effects. Therefore, the development of non-invasive devices that selectively target the vagus nerve fibers with a low risk profile has gained interest. Transcutaneous auricular VNS (tVNS) is such a non-invasive neurostimulation modality that targets the cutaneous receptive field of the auricular branch of the vagus nerve located in the outer ear. Up to date, tVNS has been investigated as a potential treatment for epilepsy with inconsistent results. The goal of this study is to investigate the effect of tVNS on cortical excitability. This will provide important insight into the underlying effects of this technique on brain neurophysiology. Cortical excitability will be investigated by combining transcranial magnetic stimulation with electromyography (TMS-EMG) and electroencephalography (TMS-EEG), evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs).
In this prospective, single-blind, cross-over study, we will include 15 healthy male participants. They will undergo a TMS safety screening (TSS) questionnaire and clinical neurological examination before inclusion. Each participant will complete 2 sessions at least one week apart, one with active tVNS and one with sham tVNS.
The intervention is tVNS by means of the Nemos® device which stimulates the cymba conchae at the outer ear. Stimulation parameters are set to a frequency of 25 Hz, a pulsewidth of 250 µs, 7 s ON, 18 s OFF. The output current is ramped up until the user feels a tingling sensation at the stimulation site, but should remain subthreshold to painful stimulation. Stimulation is delivered during 60 min.Sham stimulation is achieved by placing the electrode on the earlobe instead of the cymba conchae.
Before and after the intervention 120 single TMS pulses, 120 paired pulses with an interstimulus interval of 3ms and 120 paired pulses with an interstimulus interval of 100ms will be delivered over the right motor hotspot. MEPs will be measured at the left first dorsal interosseus muscle. TEPs will be measured using a 64-channel TMS-compatible electrode cap. MEPS and TEPS will be preprocessed offline in Matlab. TEP and MEP morphology ( amplitude and latency) will be evaluated before and after the intervention to investigate changes in cortical excitability.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Each participant will complete 2 sessions at least one week apart, one with active tVNS and one with sham tVNS.
| Arm | Type | Receives |
|---|---|---|
| Group of healthy volunteers (part I) | Experimental | Procedure: actual tVNSParticipants will undergo active tVNS. |
| Group of healthy volunteers (part II) | Sham comparator | Procedure: sham tVNSParticipants will undergo sham tVNS. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- estimated IQ > 70
- healthy volunteer, taken from anamensis, clinical neurological examination and clinical estimation of researcher
- no history of central neurological condition
- no treatment with neurotropic drugs
- TMS safety screening questionnaire
Key exclusion criteria (2 listed)
- intracranial metal objects/materials (excl teeth fillings): vascular clips, shrapnell electrodes below stimulation area
- pacemaker, implanted defibrillator, permanent medication pump, cochlear implant or deep brain stimulation (DBS)
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 |
|---|---|---|
| actual tVNSActive tVNS (stimulation on cymba conchae --> nervus vagus stimulation) | Procedure or surgery | Group of healthy volunteers (part I) |
| sham tVNSSham tVNS (stimulation on earlobe --> no nervus vagus stimulation) | Procedure or surgery | Group of healthy volunteers (part II) |
Primary outcome
Measuring the electric activity of the brain evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs) during transcutaneous nervus vagus stimulation.
Time frame: 60 minutes
Using transcranial magnetic stimulation (TMS), the influence of the tVNS is measured.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2022.
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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.
Paul Boon, MD, PhD principal investigator
University Hospital, Ghent
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing actual tVNS in people with Epilepsy, run by University Ghent at 1 site in Belgium.
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 6 inclusion and 2 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: finished, as of the sponsor's last update on 6 Dec 2022. 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 Belgium. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Measuring the electric activity of the brain evaluating changes in motor evoked potentials (MEPs) and TMS-evoked potentials (TEPs) during transcutaneous nervus vagus stimulation. (time frame: 60 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 6 Dec 2022.