Investigating the Neurophysiology of the Motor System and the Feasibility of Vagus Nerve Stimulation in Functional Neurological Disorder (FND) (TMS-VNS)
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.
研究概览
地位
详细说明
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.
研究类型
注册 (估计的)
阶段
- 不适用
联系人和位置
学习联系方式
- 姓名：Michael Mouthon, PhD
- 电话号码：+41 26 300 85 39
- 邮箱：michael.mouthon@unifr.ch
研究联系人备份
- 姓名：Selma Aybek, Professor
- 电话号码：+41 26 306 38 02
- 邮箱：selma.aybek@unifr.ch
学习地点
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Canton of Fribourg
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Fribourg、Canton of Fribourg、瑞士、1700
- University of Fribourg
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接触：
- Michael Mouthon, PhD
- 电话号码：+41 26 300 85 39
- 邮箱：michael.mouthon@unifr.ch
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副研究员：
- Michael Mouthon, PhD
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接触：
- Selma Aybek, Professor
- 电话号码：+41 26 306 38 02
- 邮箱：selma.aybek@unifr.ch
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副研究员：
- Cristina Concetti, PhD
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副研究员：
- Julia Paratte, Master
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副研究员：
- Janne Magnin, Bachelor
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副研究员：
- Sarah Botman, Bachelor
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
描述
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.
学习计划
研究是如何设计的？
设计细节
- 主要用途：支持治疗
- 分配：随机化
- 介入模型：阶乘赋值
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：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.
其他名称：
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假比较器：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).
其他名称：
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无干预：Heathy control without intervention
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Self-reported quality of life
大体时间：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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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Neurophysiology investigation of the pathology by comparing Motor-Evoked Potential between FND patients and healthy participant
大体时间：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
大体时间：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
大体时间：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
大体时间：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.
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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
大体时间：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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合作者和调查者
调查人员
- 研究主任：Cristina Concetti, PhD、University of Fribourg
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
IPD 计划说明
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 共享时间框架
IPD 共享支持信息类型
- 分析代码
药物和器械信息、研究文件
研究美国 FDA 监管的药品
研究美国 FDA 监管的设备产品
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