Investigating the Neurophysiology of the Motor System and the Feasibility of Vagus Nerve Stimulation in Functional Neurological Disorder (FND) (TMS-VNS)
2026年7月16日 更新者：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.
調査の概要
状態
まだ募集していません
詳細な説明
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.
研究の種類
介入
入学 (推定)
68
段階
- 適用できない
連絡先と場所
このセクションには、調査を実施する担当者の連絡先の詳細と、この調査が実施されている場所に関する情報が記載されています。
研究連絡先
- 名前：Michael Mouthon, PhD
- 電話番号：+41 26 300 85 39
- メール：michael.mouthon@unifr.ch
研究連絡先のバックアップ
- 名前：Selma Aybek, Professor
- 電話番号：+41 26 306 38 02
- メール：selma.aybek@unifr.ch
研究場所
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Canton of Fribourg
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Fribourg、Canton of Fribourg、スイス、1700
- University of Fribourg
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コンタクト：
- Michael Mouthon, PhD
- 電話番号：+41 26 300 85 39
- メール：michael.mouthon@unifr.ch
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副調査官：
- Michael Mouthon, PhD
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コンタクト：
- Selma Aybek, Professor
- 電話番号：+41 26 306 38 02
- メール：selma.aybek@unifr.ch
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副調査官：
- Cristina Concetti, PhD
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副調査官：
- Julia Paratte, Master
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副調査官：
- Janne Magnin, Bachelor
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副調査官：
- Sarah Botman, Bachelor
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参加基準
研究者は、適格基準と呼ばれる特定の説明に適合する人を探します。これらの基準のいくつかの例は、人の一般的な健康状態または以前の治療です。
適格基準
就学可能な年齢
- 大人
- 高齢者
健康ボランティアの受け入れ
はい
説明
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.
研究計画
このセクションでは、研究がどのように設計され、研究が何を測定しているかなど、研究計画の詳細を提供します。
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：支持療法
- 割り当て：ランダム化
- 介入モデル：階乗代入
- マスキング：ダブル
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：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.
他の名前：
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偽コンパレータ：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).
他の名前：
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介入なし：Heathy control without intervention
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Self-reported quality of life
時間枠：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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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Neurophysiology investigation of the pathology by comparing Motor-Evoked Potential between FND patients and healthy participant
時間枠：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
時間枠：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
時間枠：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
時間枠：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.
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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
時間枠：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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協力者と研究者
ここでは、この調査に関係する人々や組織を見つけることができます。
スポンサー
捜査官
- スタディディレクター：Cristina Concetti, PhD、University of Fribourg
研究記録日
これらの日付は、ClinicalTrials.gov への研究記録と要約結果の提出の進捗状況を追跡します。研究記録と報告された結果は、国立医学図書館 (NLM) によって審査され、公開 Web サイトに掲載される前に、特定の品質管理基準を満たしていることが確認されます。
主要日程の研究
研究開始 (推定)
2026年7月1日
一次修了 (推定)
2028年7月1日
研究の完了 (推定)
2028年12月1日
試験登録日
最初に提出
2026年6月24日
QC基準を満たした最初の提出物
2026年7月16日
最初の投稿 (実際)
2026年7月17日
学習記録の更新
投稿された最後の更新 (実際)
2026年7月17日
QC基準を満たした最後の更新が送信されました
2026年7月16日
最終確認日
2026年7月1日
詳しくは
本研究に関する用語
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
はい
IPD プランの説明
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.
IPD 共有時間枠
The public repositories would be made available to the public after the publication date of the relevant scientific article.
IPD 共有サポート情報タイプ
- ANALYTIC_CODE
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米国FDA規制医薬品の研究
いいえ
米国FDA規制機器製品の研究
いいえ
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