Non Invasive Neuromodulation for Patients With Motor Control Disorders

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Other: Repetitive transcranial magnetic stimulation (rTMS); Other: EEG guided Neurofeedback (NFB)

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Repetitive stimulating transcranial stimulation (rTMS); 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); 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.
Experimental: EEG guided Neurofeedback (NFB); 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); 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.
Experimental: rTMS + NFB; Subjects receive both interventions sequentially	Other: Repetitive transcranial magnetic stimulation (rTMS); 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.; Other: EEG guided Neurofeedback (NFB); 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.
No Intervention: No intervention; No interventions, the patient just comes to be evaluated sequentially according to the timing of experimental groups.

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Universidad Francisco de Vitoria
• Collaborators: National Research Council, Spain; Hospital Universitario de Fuenlabrada; Hospital Beata María Ana

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2016
• Primary Completion (Actual): December 20, 2018
• Study Completion (Actual): September 30, 2019

Study Registration Dates

• First Submitted: July 2, 2019
• First Submitted That Met QC Criteria: July 11, 2019
• First Posted (Actual): July 12, 2019

Study Record Updates

• Last Update Posted (Actual): November 20, 2020
• Last Update Submitted That Met QC Criteria: November 19, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Keywords: neuromodulation; TMS; NFB
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Parkinson Disease
• Other Study ID Numbers: NeuroMOD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual anonymized participant data will be available to other researchers under request.
• IPD Sharing Time Frame: six months after the end of the study
• IPD Sharing Access Criteria: Individual anonymized participant data will be available to other researchers under request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No