Functional Neurological DisorderTMS-VNSNCT07710677
Investigating the Neurophysiology of the Motor System and the Feasibility of Vagus Nerve Stimulation in Functional Neurological Disorder (FND)
A study testing Vagial Nerve Stimulation (VNS) active stimulation in people with Functional Neurological Disorder and Motor Symptoms, run by University of Fribourg at 1 site in Switzerland.
Trial summary
This clinical study will test if adding a non-invasive stimulation of the vagus nerve through the ear during physiotherapy brings an improvement to FND (Functional Neurological Disorder) patients with motor symptoms. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Functional Neurological Disorder, Motor Symptoms
- What is being tested?
- Vagial Nerve Stimulation (VNS) active stimulation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 1 siteSwitzerland
- Study dates
- 1 Jul 2026to 1 Dec 2028
- Phase
- Interventional
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Over 18 years of age.
- Capable of judgement.
- Willing to participate in the study (by signing the informed consent form).
- FND diagnosis by a certified neurologist or psychiatrist.
- Motor FND symptoms in the upper limb in the form of tremor or weakness.
- Participating in physiotherapy for FND.
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- Over 18 years of age.
- Capable of judgement.
- Willing to participate in the study (by signing the informed consent form).
Who cannot join
- Severe neuropsychiatric comorbidities.
- Pregnancy or breastfeeding.
- Prior knowledge on the effects of attention on the motor system.
- Prior history of epilepsy or epileptic seizures in the person and their family.
- Severe claustrophobia.
- Implanted medical devices.
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- Ear anatomy incompatible with the taVNS device (e.g. cauliflower ear).
- Previous use of taVNS.
- Substance abuse.
- Simultaneous participation in another investigation involving an investigational drug or a MD.
- Enrolment of the PI and their dependent persons.
- Neurological or neuropsychiatric or movement disorders.
- Pregnancy or breastfeeding.
- Prior knowledge on the effects of attention on the motor system.
- Prior history of epilepsy or epileptic seizures in the person and their family.
- Substance abuse.
- Simultaneous participation in another investigation involving an investigational drug or a MD.
- Enrolment of the PI and their dependent persons.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site
University of Fribourg
Fribourg, Canton of Fribourg, 1700
Selma Aybek, Professor, +41 26 306 38 02, selma.aybek@unifr.ch
Michael Mouthon, PhD, +41 26 300 85 39, michael.mouthon@unifr.ch
About this study
Official title: Investigating the Neurophysiology of the Motor System and the Feasibility of Vagus Nerve Stimulation in Functional Neurological Disorder (FND): a Randomized, Sham-controlled Study
This clinical study will test if adding a non-invasive stimulation of the vagus nerve through the ear during physiotherapy brings an improvement to FND (Functional Neurological Disorder) patients with motor symptoms.
First, the investigators will test the normal functioning of the motor regions of the brain in FND patients and in healthy volunteers for comparison, using a painless method called TMS (Transcranial Magnetic Stimulation). Then, the investigators will further test how brain regions communicate with each other in FND patients, using fMRI (functional Magnetic Resonance Imaging, also painless). Additionally, the investigators will ask both FND patients and healthy volunteers to answer questions about their health and wellbeing, and will assess the exact symptoms of FND patients. The FND patients will then be assigned to two groups randomly, and neither they nor the researchers will know in which group they are. Both groups will do 5 sessions of their usual physiotherapy - one group with a real stimulation of the vagus nerve, and the other group with a fake stimulation. This is important to obtain reliable results. At the end, both groups of patients will be tested again to see if the way brain regions communicate with each other has changed. They will also answer again questions about their health and wellbeing, and their symptoms will be assessed again, to see if any changes happen. The results of the two groups of patients will be compared to isolate the effects of vagus nerve stimulation from the effects of physiotherapy alone.
Read the detailed description
The main goal of this project is to better understand the neurophysiology of the motor system and the role of attention in Functional Neurological Disorder (FND) and to explore the physiological effects of a novel non-invasive treatment option for this disorder.
To this end, several methods will be employed: non-invasive brain stimulation (using Transcranial Magnetic Stimulation, TMS), neuroimaging (fMRI), transdermal auricular vagus nerve stimulation (taVNS), clinical assessments and questionnaires.
The study consists of 2 experiments, each with specific objectives.
Primary objective:
The primary objective of this study is to assess the effects of taVNS, as an adjunctive intervention to standard physical therapy, on the quality of life in FND patients.
Secondary objectives:
Experiment 1
- Assess baseline neurophysiological differences of the motor system at rest and under different attentional demands, between FND patients and healthy participants.
- Compare the motor behaviour of the upper limb (index finger) under different attentional demands, in FND patients and healthy participants.
- Explore the role of symptom severity, mood, physical health, and interoception (the perception of bodily signals), assessed by questionnaires, in the modulation of motor system neurophysiology in FND patients and healthy participants.
- Explore the relationship between neurophysiological (point 1) and behavioral (point 2) outcomes, and the outcomes of clinical and psychological scores measured (point 3).
Experiment 2
- Assess the feasibility of the taVNS intervention as an adjunctive treatment in FND.
- Determine whether adding taVNS to standard physical therapy improves clinical outcomes (motor symptoms) in FND patients, assessed by clinical scores (CGI, sFMDRS).
- Explore changes in self-reported measures of mood, stress, physical health and interoception (the perception of bodily signals), assessed by questionnaires, after taVNS in FND patients.
- Explore changes in upper limb strength, measured by a grip strength test with hand-held dynamometer under different starting conditions (pressing freely and pressing after a cue), before, during and after taVNS in FND.
- Assess the effect of taVNS on heart rate and heart rate variability (HRV) in FND patients.
- Analyse the modulation of brain network connectivity via fMRI at rest and during a behavioural task (emotion-motion task), before and after taVNS in FND patients.
- Explore the relationship between neuroimaging (point 6), behavioral (point 2) outcomes, and the outcomes of clinical and psychological scores measured (point 3).
An additional outcome will explore the relationship between the outcomes of Experiment 1 and Experiment 2 to assess the prognostic potential of the outcomes of Experiment 1.
- Conditions
- Functional Neurological Disorder, Motor Symptoms
- Being tested
- Vagial Nerve Stimulation (VNS) active stimulation, Vagial Nerve Stimulation (VNS) sham stimulation
- Keywords
- Functional Neurological Disorder, FND, vagus nerve stimulation, VNS, TMS, fMRI, motor
- Medical subject headings
- Conversion Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vagial Nerve Stimulation (VNS) active stimulationDevice
Also called taVNS, tVNS, active
taVNS sends gentle electric stimuli to the vagus nerve branch located in the outer ear, which are transmitted to the nucleus of the solitary tract in the brainstem, and from there to the rest of the brain. The electrode site is the cymba conchae in in the outer ear. VNS thus acts to enhance the activity of the parasympathetic nervous system.
Vagial Nerve Stimulation (VNS) sham stimulationDevice
Also called taVNS, tVNS, sham
taVNS sends gentle electric stimuli for several minutes, during which time the patient will feel a tickling sensation. Then, for the rest of the session, the hidden device will be switched off (there will be no stimulation).
| Study group | Role | What they receive |
|---|---|---|
| Patient VNS stimulation intervention | Experimental | FND patients received a 30 minutes VNS stimulation for 5 sessions during their usual physiotherapy course treatment. Receives: Device: Vagial Nerve Stimulation (VNS) active stimulation |
| Patient VNS sham intervention | Sham comparator | FND patients received a 30 minutes VNS sham for 5 sessions during their usual physiotherapy course treatment. Receives: Device: Vagial Nerve Stimulation (VNS) sham stimulation |
| Heathy control without intervention | No intervention | Heathy control without intervention |
What is being measured
The primary outcome is the main question the study is designed to answer.
Self-reported quality of life
The change in self-reported quality of life, measured through intervention sessions with the Euro Quality of Life questionnaire (EQ-5D-5L), compared between the active stimulation group and the sham stimulation group. This questionnaire includes 5 subscales (1-best, 5-worstest) about mobility, self-care, usual activities, pain/discomfort, anxiety/depression. In addition it includes a continue scale evaluation (0-worst to 100-best) about the patient evaluation on his health.
Measured: For each intervention session at weeks 3, 4, 5, 6, 7
Secondary outcomes (16)
Neurophysiology investigation of the pathology by comparing Motor-Evoked Potential between FND patients and healthy participant
The study will examine cortical inhibition as measured by motor-evoked potentials (MEPs) during a short-interval intracortical inhibition (SICI) transcranial magnetic stimulation (TMS) protocol (single-pulse and paired-pulse). The investigators will examine how the outcome differs under different attentional demands in patients with functional neurological disorder (FND) and healthy participants.
Measured: At TMS session, week 2 for patients and week 0 for heathy controls
Neurophysiology investigation of the pathology by comparing resting motor threshold between FND patients and healthy participant
The study will examine the resting motor threshold (in millivolts), which is the level of stimulation required to trigger motor-evoked potentials using a single-pulse transcranial magnetic stimulation (TMS) technique. The investigators will examine how this outcome differs between patients with functional neurological disorder (FND) and healthy participants.
Measured: At TMS session, week 2 for patients and week 0 for heathy controls
Comparison of motor performance between patients and healthy controls
The differences in motor performance between FND patients and healthy controls were measured by the accuracy with which they maintained an isometric contraction during index finger abduction at 10% of maximum force.
Measured: At TMS session, week 2 for patients and week 0 for heathy controls
Satisfaction rating of patients on the intervention
Patients will be asked to rate their satisfaction after the intervention on a scale from 1 to 10.
Measured: At the end of the last intervention session at week 7
Changes in upper limb strength, measured by a grip strength test under different starting conditions, before, during and after taVNS intervention.
Grip strength measured with hand-held dynamometer (Jamar). The different starting condition was pressing freely or pressing after a cue.
Measured: weeks 2, 3, 4, 5, 6, 7
Changes in parasympathetic tone measured by heart rate variability
A sport belt would continuously record the heart rate of patients during physiotherapy sessions.
Measured: During intervention sessions at weeks 3, 4, 5, 6, 7
Change in functional connectivity, measured by resting-state fMRI
Study the differences in functional connectivity of the brain in patients at the beginning and end of the experimental protocol.
Measured: weeks 0, 8
General heath condition questionnaire
Use of the questionnaire SF-36 (Medical Outcomes Study Short Form Health Survey) fill by participants to evaluate their heath condition (score between 0-bad and 100-good).
Measured: week 0
Study the evolution of symptom severity score
The patients completed the Subjective Evaluation of Symptom Severity (SSS) questionnaire, which uses a continuous scale ranging from 0 (no symptoms) to 100 (the most severe symptoms experienced) for each session. For the intervention sessions, they fill it twice (before and after the intervention).
Measured: weeks 1, 2, 3, 4, 5, 6, 7, 8
Study evolution of perceived stress
The patients completed the Perceived Stress Scale (PSS) questionnaire with 4 items, which uses a score from 4 (no stress) to 20 (extremely stressed). For the intervention sessions, they fill it twice (before and after the intervention).
Measured: weeks 1, 2, 3, 4, 5, 6, 7, 8
Study the evolution of the clinical global impression score
The investigator will assess the severity of the patient's symptoms using a scale ranging from 0 (normal, not at all unwell) to 7 (among the most severely unwell) at each session. For the intervention sessions, the evaluation is done twice (before and after the intervention).
Measured: weeks 1, 2, 3, 4, 5, 6, 7, 8
Study the evolution of depression evaluation
The patients completed the Beck Depression Inventory (BDI-II) questionnaire before and after the intervention period. The questionnaire uses a score ranging from 0 (not depressed) to 63 (extremely depressed).
Measured: weeks 2, 8
Study the evolution of stress evaluation
The patients completed the State-Trait Anxiety Inventory (STAI) questionnaire before and after the intervention period. The questionnaire uses a score ranging from 20 (not stressed) to 80 (extremely stressed) for the state and the trait separetely.
Measured: weeks 2, 8
Study the evolution of interoception evaluation
The patients completed the Multidimensional Assessment of Interoceptive Awareness (MAIA) questionnaire before and after the whole protocol. The questionnaire uses a score ranging from 0 (poor interoceptive sensitivity) to 40 (excellent interoceptive sensitivity).
Measured: weeks 0, 8
Study the evolution of functional movement disorders rating scale
The investigator performed Simplified Functional Movement Disorders Rating Scale (sFMDRS) questionnaire before and after the intervention period. The questionnaire uses a score ranging from 0 (no symptoms) to 48 (extremely symptomatic).
Measured: weeks 0, 8
Satisfaction rating of physiotherapists on the intervention
Physiotherapists will be asked to rate their satisfaction after the intervention on a scale from 1 to 10.
Measured: At the end of the last intervention session at week 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jul 2026
- Study start1 Jul 2026 (estimated)
- Primary completion1 Jul 2028 (estimated)
- Study completion1 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Functional Neurological DisorderStudies 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- Patients will be assigned either to intervention or placebo for the VNS part. The healthy control will not participate to the VNS intervension but to the other part of the study (MRI, TMS).
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 68 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Fribourg
- Sponsor type
- University, hospital or other
- Collaborators
- Hôpital Fribourgeois
- Responsible party
- Sponsor
- Investigators
- Cristina Concetti, PhD, Study director, University of Fribourg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07710677
- Sponsor's protocol ID
- 2026-D0047
- Acronym
- TMS-VNS
- Status last verified
- Jul 2026
- First submitted
- 24 Jun 2026
- Last updated
- 17 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Participants had the option of signing an informed consent form to allow their coded data to be shared with the scientific community. At the end of the project, the de-identified raw data would be published in a public repository on the Zenodo platform.