Investigating the Neurophysiology of the Motor System and the Feasibility of Vagus Nerve Stimulation in Functional Neurological Disorder (FND) (TMS-VNS)
16. července 2026 aktualizováno: University of Fribourg
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.
Přehled studie
Postavení
Zatím nenabíráme
Detailní popis
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.
Typ studie
Intervenční
Zápis (Odhadovaný)
68
Fáze
- Nelze použít
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní kontakt
- Jméno: Michael Mouthon, PhD
- Telefonní číslo: +41 26 300 85 39
- E-mail: michael.mouthon@unifr.ch
Studijní záloha kontaktů
- Jméno: Selma Aybek, Professor
- Telefonní číslo: +41 26 306 38 02
- E-mail: selma.aybek@unifr.ch
Studijní místa
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Canton of Fribourg
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Fribourg, Canton of Fribourg, Švýcarsko, 1700
- University of Fribourg
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Kontakt:
- Michael Mouthon, PhD
- Telefonní číslo: +41 26 300 85 39
- E-mail: michael.mouthon@unifr.ch
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Dílčí vyšetřovatel:
- Michael Mouthon, PhD
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Kontakt:
- Selma Aybek, Professor
- Telefonní číslo: +41 26 306 38 02
- E-mail: selma.aybek@unifr.ch
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Dílčí vyšetřovatel:
- Cristina Concetti, PhD
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Dílčí vyšetřovatel:
- Julia Paratte, Master
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Dílčí vyšetřovatel:
- Janne Magnin, Bachelor
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Dílčí vyšetřovatel:
- Sarah Botman, Bachelor
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Ano
Popis
Inclusion Criteria for FND patients:
- 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.
Exclusion Criteria for FND patients:
- 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.
- 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.
Inclusion Criteria for healthy volunteers:
- Over 18 years of age.
- Capable of judgement.
- Willing to participate in the study (by signing the informed consent form).
Exclusion Criteria for healthy volunteers:
- 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.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
- Primární účel: Podpůrná péče
- Přidělení: Randomizované
- Intervenční model: Faktorové přiřazení
- Maskování: Dvojnásobek
Zbraně a zásahy
Skupina účastníků / Arm |
Intervence / Léčba |
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Experimentální: Patient VNS stimulation intervention
FND patients received a 30 minutes VNS stimulation for 5 sessions during their usual physiotherapy course treatment.
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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.
Ostatní jména:
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Falešný srovnávač: Patient VNS sham intervention
FND patients received a 30 minutes VNS sham for 5 sessions during their usual physiotherapy course treatment.
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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).
Ostatní jména:
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Žádný zásah: Heathy control without intervention
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Self-reported quality of life
Časové okno: For each intervention session at weeks 3, 4, 5, 6, 7
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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.
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For each intervention session at weeks 3, 4, 5, 6, 7
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Neurophysiology investigation of the pathology by comparing Motor-Evoked Potential between FND patients and healthy participant
Časové okno: At TMS session, week 2 for patients and week 0 for heathy controls
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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.
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At TMS session, week 2 for patients and week 0 for heathy controls
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Neurophysiology investigation of the pathology by comparing resting motor threshold between FND patients and healthy participant
Časové okno: At TMS session, week 2 for patients and week 0 for heathy controls
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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.
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At TMS session, week 2 for patients and week 0 for heathy controls
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Comparison of motor performance between patients and healthy controls
Časové okno: At TMS session, week 2 for patients and week 0 for heathy controls
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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.
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At TMS session, week 2 for patients and week 0 for heathy controls
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Satisfaction rating of patients on the intervention
Časové okno: At the end of the last intervention session at week 7
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Patients will be asked to rate their satisfaction after the intervention on a scale from 1 to 10.
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At the end of the last intervention session at week 7
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Changes in upper limb strength, measured by a grip strength test under different starting conditions, before, during and after taVNS intervention.
Časové okno: weeks 2, 3, 4, 5, 6, 7
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Grip strength measured with hand-held dynamometer (Jamar).
The different starting condition was pressing freely or pressing after a cue.
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weeks 2, 3, 4, 5, 6, 7
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Changes in parasympathetic tone measured by heart rate variability
Časové okno: During intervention sessions at weeks 3, 4, 5, 6, 7
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A sport belt would continuously record the heart rate of patients during physiotherapy sessions.
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During intervention sessions at weeks 3, 4, 5, 6, 7
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Change in functional connectivity, measured by resting-state fMRI
Časové okno: weeks 0, 8
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Study the differences in functional connectivity of the brain in patients at the beginning and end of the experimental protocol.
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weeks 0, 8
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General heath condition questionnaire
Časové okno: week 0
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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).
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week 0
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Study the evolution of symptom severity score
Časové okno: weeks 1, 2, 3, 4, 5, 6, 7, 8
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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).
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weeks 1, 2, 3, 4, 5, 6, 7, 8
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Study evolution of perceived stress
Časové okno: weeks 1, 2, 3, 4, 5, 6, 7, 8
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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).
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weeks 1, 2, 3, 4, 5, 6, 7, 8
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Study the evolution of the clinical global impression score
Časové okno: weeks 1, 2, 3, 4, 5, 6, 7, 8
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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).
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weeks 1, 2, 3, 4, 5, 6, 7, 8
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Study the evolution of depression evaluation
Časové okno: weeks 2, 8
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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).
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weeks 2, 8
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Study the evolution of stress evaluation
Časové okno: weeks 2, 8
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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.
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weeks 2, 8
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Study the evolution of interoception evaluation
Časové okno: weeks 0, 8
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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).
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weeks 0, 8
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Study the evolution of functional movement disorders rating scale
Časové okno: weeks 0, 8
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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).
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weeks 0, 8
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Satisfaction rating of physiotherapists on the intervention
Časové okno: At the end of the last intervention session at week 7
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Physiotherapists will be asked to rate their satisfaction after the intervention on a scale from 1 to 10.
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At the end of the last intervention session at week 7
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Spolupracovníci
Vyšetřovatelé
- Ředitel studie: Cristina Concetti, PhD, University of Fribourg
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Odhadovaný)
1. července 2026
Primární dokončení (Odhadovaný)
1. července 2028
Dokončení studie (Odhadovaný)
1. prosince 2028
Termíny zápisu do studia
První předloženo
24. června 2026
První předloženo, které splnilo kritéria kontroly kvality
16. července 2026
První zveřejněno (Aktuální)
17. července 2026
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
17. července 2026
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
16. července 2026
Naposledy ověřeno
1. července 2026
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- 2026-D0047
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
ANO
Popis plánu IPD
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.
Časový rámec sdílení IPD
The public repositories would be made available to the public after the publication date of the relevant scientific article.
Typ podpůrných informací pro sdílení IPD
- ANALYTIC_CODE
Informace o lécích a zařízeních, studijní dokumenty
Studuje lékový produkt regulovaný americkým FDA
Ne
Studuje produkt zařízení regulovaný americkým úřadem FDA
Ne
Tyto informace byly beze změn načteny přímo z webu clinicaltrials.gov. Máte-li jakékoli požadavky na změnu, odstranění nebo aktualizaci podrobností studie, kontaktujte prosím register@clinicaltrials.gov. Jakmile bude změna implementována na clinicaltrials.gov, bude automaticky aktualizována i na našem webu .
Klinické studie na Vagial Nerve Stimulation (VNS) active stimulation
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Gaziler Physical Medicine and Rehabilitation Education...NáborPoranění míchy (SCI)Krocan