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| Name | Class |
|---|---|
| Hôpital Cantonal de Fribourg | OTHER_GOV |
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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.
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
Experiment 2
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Patient VNS stimulation intervention | Experimental | FND patients received a 30 minutes VNS stimulation for 5 sessions during their usual physiotherapy course treatment. |
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| Patient VNS sham intervention | Sham Comparator | FND patients received a 30 minutes VNS sham for 5 sessions during their usual physiotherapy course treatment. |
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| Heathy control without intervention | No Intervention | Heathy control without intervention |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Vagial Nerve Stimulation (VNS) active stimulation | Device | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | For each intervention session at weeks 3, 4, 5, 6, 7 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
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Inclusion Criteria for FND patients:
Exclusion Criteria for FND patients:
Inclusion Criteria for healthy volunteers:
Exclusion Criteria for healthy volunteers:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Selma Aybek, Professor | Contact | +41 26 306 38 02 | selma.aybek@unifr.ch | |
| Michael Mouthon, PhD | Contact | +41 26 300 85 39 | michael.mouthon@unifr.ch |
| Name | Affiliation | Role |
|---|---|---|
| Cristina Concetti, PhD | University of Fribourg | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Fribourg | Fribourg | Canton of Fribourg | 1700 | Switzerland |
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.
The public repositories would be made available to the public after the publication date of the relevant scientific article.
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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).
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In addition, half of the investigator will be blind of the intervention groups.
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| Vagial Nerve Stimulation (VNS) sham stimulation | Device | 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). |
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| 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. | 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. | 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. | 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. | 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. | 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. | 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). | 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). | 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). | 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). | 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). | 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. | 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). | 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). | 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. | At the end of the last intervention session at week 7 |
| ID | Term |
|---|---|
| D003291 | Conversion Disorder |
| ID | Term |
|---|---|
| D013001 | Somatoform Disorders |
| D001523 | Mental Disorders |
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