Non Invasive Neuromodulation for Patients With Motor Control Disorders

Study Overview
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Brief Summary
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Movement disorders are neurological syndromes leading to excessive movements or to limited control of voluntary and automatic movements. Many of these disorders are not life-threatening but represent serious difficulties in carrying out the activities of daily living and reduce patient's independence and quality of life. This project NeuroMOD (neuromodulation for patients with disorders of motor control) proposes the development of a neuromodulation-based platform for the rehabilitation and restoration of motor and cognitive functions of patients suffering from Parkinson's disease (PD). Our project will focus on the application of a novel neurorehabilitation strategy, its functional and clinical validation, and on the evaluation of the impact of the use of the technologies involved in the musculoskeletal and the nervous system as well as user behavior. Parkinson's disease was selected as target pathology since it represents a paradigm of motor disorder diseases. Parkinson's disease affects adults and has a very high prevalence and a very high functional impact. In order to achieve this objective, we have defined the following research areas: Subproject 1. NeuroMOD: development of a neuromodulation platform composed by a TMS system, and an EMG (electromyography) and EEG (electroencephalography) system in combination with a system of virtual reality based on immersive glasses. Subproject 2. NeuroMOD-PD: development of therapies and evaluation of clinical evidence and motor and cognitive impact of NeuroMOD in the rehabilitation of patients suffering from Parkinson's disease impact. Subproject 3. NeuroMOD-Image: development of neuroimaging techniques to investigate the brain areas affected by the proposed therapies and temporary terms that neural plasticity is induced and evolves in Parkinson´s Disease.

Official Title
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Development and Clinical Validation of a Rehabilitation Platform Based on Neuromodulation for Patients With Motor Control Disorders

Conditions
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Parkinson Disease

Intervention / Treatment
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* Other: Repetitive transcranial magnetic stimulation (rTMS)
* Other: EEG guided Neurofeedback (NFB)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Idiopathic Parkinsons Disease Hoehn Yahr Scale I-III No drug changes in the last 90 days No exclusion criteria Exclusion Criteria: Dementia (Minimental scale score <25) Dependency (modified Rankin scale > 3) Pregnancy or pregnancy plans Pacemaker Implanted metal devices cochlear implants claustrophobia drug infusion pumps epilepsy / epileptiform anomalies in electroencephalography (EEG) known structural alterations in magnetic resonance imaging (MRI) Atypical Parkinsonism Previous repetitive transcranial magnetic stimulation (rTMS) Severe comorbidity (cancer, severe debilitating diseases, etc.)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: Each study participant is assigned to one of the arms. Four intervention groups are defined as rTMS only, NFB only, both TMS and NFB, or neither TMS or NFB
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Repetitive stimulating transcranial stimulation (rTMS)<br>Subjects receive 8 sessions M1 Neuromodulation using rTMS according to the protocol ( 80% resting motor threshold, 10 Hertz; 1000 pulses; 25 trains de 4 seconds con 25 seconds intertrain. | Other: Repetitive transcranial magnetic stimulation (rTMS)<br>* The intervention intends to change the cortical plasticity in specific cortical areas. rTMS is a non-invasive exogenous neuromodulation technique that uses repetitive magnetic pulses administered in a specific area of the head in order to influence the connectivity of the underlying brain area.<br>|
| Experimental: EEG guided Neurofeedback (NFB)<br>Subjects receive 8 sessions M1 EEG guided NFB with virtual reality goggles in order to modify the beta rhythm. The sessions have a duration of 20min | Other: EEG guided Neurofeedback (NFB)<br>* The intervention intends to change the cortical plasticity in specific cortical areas. The NFB is a non-invasive endogenous technique that seeks the self-regulation of cortical activity through the information represented in a videogame which is used to interact with the subject.<br>|
| Experimental: rTMS + NFB<br>Subjects receive both interventions sequentially | Other: Repetitive transcranial magnetic stimulation (rTMS)<br>* The intervention intends to change the cortical plasticity in specific cortical areas. rTMS is a non-invasive exogenous neuromodulation technique that uses repetitive magnetic pulses administered in a specific area of the head in order to influence the connectivity of the underlying brain area.<br>Other: EEG guided Neurofeedback (NFB)<br>* The intervention intends to change the cortical plasticity in specific cortical areas. The NFB is a non-invasive endogenous technique that seeks the self-regulation of cortical activity through the information represented in a videogame which is used to interact with the subject.<br>|
| No Intervention: No intervention<br>No interventions, the patient just comes to be evaluated sequentially according to the timing of experimental groups. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Motor changes | UNIFIED PARKINSON'S DISEASE RATING SCALE (UPDRS) part III ( total values from 0-68, higher score worse clinical situation) | The day before the first stimulation session and 2 weeks after the first stimulation session | 
| Motor changes | UNIFIED PARKINSON'S DISEASE RATING SCALE (UPDRS) part III ( total values from 0-68, higher score worse clinical situation) | t2(2 weeks after finishing the protocol) | 
| Neurophysiological cortical changes | Cortical silent period measured using transcranial magnetic pulse in M1 and simultaneous register of electromyographical response | The day before the first stimulation session and 2 weeks after the first stimulation session | 
| Neurophysiological cortical changes | Cortical silent period measured using transcranial magnetic pulse in M1 and simultaneous register of electromyographical response | t2(2 weeks after finishing the protocol) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life changes | Changes in PDQ 39 (The 39-Item Parkinson's Disease Questionnaire) score, common range of 0-100 (100 = maximum level of problems). | t2(2 weeks after finishing the protocol) | 
| Encephalographic changes | Changes in microstates of electro encephalography (presence of state A, B, C, D and E) | t2(2 weeks after finishing the protocol) | 
| Cognitive changes in objective measures of processing speed | Changes in cognitive processing speed using computer based reaction time task | t2(2 weeks after finishing the protocol) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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neuromodulation, TMS, NFB