Virtual Reality in Physical Therapy in Multiple Sclerosis (VIREMS)

Effect of Neuroproprioceptive "Facilitation, Inhibition" Physical Therapy Using Virtual Reality on Upper Limb Mobility and Postural Stability in Multiple Sclerosis

The randomized controlled trial is aimed to study the efficacy of virtual reality (VR) and its impact on upper limb function and postural stability in people with mild to severe multiple sclerosis (pwMS). The conceptual idea is to compare two kinds of neuroproprioceptive "facilitation and inhibition" physical therapy, first in a real environment and second in virtual reality, in out-patient therapy that will be held in 15 hourly therapies, 2x a week in a period of two months. The efficacy will be assessed by a blinded independent clinical examiner using clinical examination and questionnaire survey before and in a week following the therapeutic intervention. The main focus is on upper limb gross and fine motor skills, trunk stability and stability, and sit to stand stability.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Neuroproprioceptive "facilitation and inhibition"; Device: Neuroproprioceptive "facilitation and inhibition" in virtual reality

Detailed Description

In 60 - 75% of people with multiple sclerosis (MS) an upper limb mobility dysfunction (unilateral or bilateral manual dexterity, sensibility impairment, tremor) is present, resulting in reduced participation in activities of daily living.

Physiotherapy has a crucial impact on upper limb mobility, although there are many approaches applied (exercise/strengthening exercise, endurance training, sensory training, constraint-induced movement therapy, robotic rehabilitation therapy, etc.).

Virtual reality is an innovative technological concept using game mechanisms that facilitate concentration and motivation in task performance. Current research implies that VR is a safe and effective method in gait and balance//stability rehabilitation therapy and with less evidence, for upper limb mobility improvement. It is expected that a greater therapeutic effect is a result of multifactorial sense stimulation and dopamine centres in the brain.

A pilot project showed that virtual reality without the prompt feedback of a physiotherapist is not more effective than standard therapy. A new therapeutic software using virtual reality spontaneously motivating the patient for movement realization was developed in cooperation with the Department of informatics and computer science Faculty of applied sciences University West Bohemia. Accurate execution of neuroproprioceptive "facilitation and inhibition techniques" physical therapy combining key principles from proprioceptive neuromuscular stabilization (PNS) and motor program activating therapy (MPAT), ensures a present physiotherapist. These principles have shown the effect in therapy in pwMS. Participants will be randomized into two arms of the study, both implementing neuroproprioceptive "facilitation and inhibition" physical therapy, first in a real environment and second in VR.

The investigators expect that VR intervention shall improve upper limb motor functions, trunk muscles coordination, improve the performance of activities of daily living and quality of life in pwMS more than identical therapy not using VR.

The effect of both interventions will be assessed using validated tests for clinical examination- Five times Sit to Stand test (5STS), Nine Hole Peg Test (9HPT), Hand Grip Strength (HGS), Box and Block Test (BNB), accelerometer for tremor examination. Validated questionnaires will be used, specifically the Multiple Sclerosis Impact Scale (MSIS-29), EQ-5D-3L health questionnaire, Visual Analogue Scale, and a questionnaire dealing with individual virtual reality intervention evaluation.

• Study Type: Interventional
• Enrollment (Anticipated): 110
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Barbora Miznerova, M.D.; Phone Number: +420776480210; Email: blahutovabarbora@seznam.cz

Study Locations

• Czechia
  • Prague, Czechia, 100 00
    • Recruiting
    • Department of Neurology
  • Prague, Czechia, 140 59
    • Recruiting
    • Deparment of revmatology and rehabilitation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• The inclusion criteria comprise of a definite diagnosis of multiple sclerosis, EDSS score ≥ 2 a ≤ 7 ((10); determined by neurologist), no history of relapse, no history of change in disease-modifying treatment, no history of corticosteroid therapy in the past three months prior to recruitment.

Exclusion Criteria:

• The exclusion criteria include other factors influencing mobility (history of stroke, pregnancy, traumatic injury of limb/s. Severe cardiovascular or orthopedic dysfunction, impaired cognitive functions in the course of examination and/or consecutive therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: SUPPORTIVE_CARE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Neuroproprioceptive "facilitation and inhibition"; ARM 1 - Neuroproprioceptive "facilitation and inhibition" physical therapy combining key principles of proprioceptive neuromuscular facilitation (PNF) and motor program activating therapy (MPAT), with former positive probative evidence on MS and are recommended for MS intervention.	Other: Neuroproprioceptive "facilitation and inhibition"; The first arm of the study will consist of a physiotherapeutic approach based on neurophysiological principles using proprioceptive neuromuscular facilitation (PNF) and motor program activating therapy (MPAT) approaches. MPAT makes use of particular motor patterns that evolve in postural control development. The repetition of activated programs, a set of stimuli, applied to change the posture with anatomical centration of the joint under various conditions in leading to better support of postural stabilization while seated, while getting up, stepping forward, and standing, in order to teach the patients to use the acquired motor skills automatically in daily life. PNF is a method used for learning effective movement patterns with high biomechanical effectiveness based on repetitive stimulation of cooperating alfa-motoneurons and proprioceptors in muscle, tendons and joint capsules. Therapy will be individualized and led in the standard face-to-face regiment.
EXPERIMENTAL: Neuroproprioceptive "facilitation and inhibition" in virtual reality; ARM 2. Experimental group, neuroproprioceptive "facilitation and inhibition" physical therapy combining key principles of proprioceptive neuromuscular facilitation (PNF) and motor program activating therapy (MPAT) through virtual reality and software inducing and motivating for movement according to principles of proprioceptive neuromuscular facilitation (PNF) and motor program activating therapy (MPAT). We believe that the VR environment might lead to better results due to greater motivation effect, novelty effect, entertainment effect, as well as activating the reward system. We believe the VR might enhance the activation of mirror neurons, it might also activate proprioception. The present physiotherapist is to ensure proper execution of the tasks. The correlation of the two arms of the study should indicate, whether virtual reality and the software used are as effective, or more effective in sustaining the hand motor function and axial stability, than traditionally led therapy.	Device: Neuroproprioceptive "facilitation and inhibition" in virtual reality; The 110 outpatients will be randomized into groups: First arm, individual neuroproprioceptive "facilitation and inhibition" physical therapy combining key principles of proprioceptive neuromuscular facilitation (PNF) and motor program activating therapy (MPAT) in a real environment and the second arm, the same therapy in virtual reality environment. All participants will undergo 15 sessions, 60 minutes each, twice a week in a period of two months. The therapy in a second, interventional group, uses virtual reality and new software that was developed specifically for inducing and motivating for movement according to principles of proprioceptive neuromuscular facilitation (PNF) and motor program activating therapy (MPAT). The software allows immediate feedback and moreover, movement is corrected by a present therapist. Evaluation of speed and performance quality might be extracted from the software of virtual reality.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Nine Hole Peg Test (9HPT) - change pre/post intervention	The NHPT requires participants to repeatedly place and then remove nine pegs into nine holes, one at a time, as quickly as possible. Lower number (quicker time) means better result.	Pre-assessment (baseline testing), Post-assessment (immediately in a week following the last procedure)
Box and Block Test (BNB) - change pre/post intervention	The Box and Block Test tests gross manual dexterity. This test consists of moving, one by one, the maximum number of blocks from one compartment of a box to another of equal size, originally, within 60 seconds. A lower number (quicker time) means better result.	Pre-assessment (baseline testing), Post-assessment (immediately in a week following the last procedure)
Five times Sit to Stand test (5STS) -change pre/post intervention	The test assesses time when people stand and sit repeatedly five times. The lower the time to complete the test the better the outcome of the test.	Pre-assessment (baseline testing), Post-assessment (immediately in a week following the last procedure)
Hand Grip Strength (HGS) -change pre/post intervention	Jamar Hydraulic Hand Dynamometer measures isometric grip force and strength. The higher value, the better function (higher strength).	Pre-assessment (baseline testing), Post-assessment (immediately in a week following the last procedure)
Frequency for which the smoothed power spectral density is maximal (fMAX)	The spectral characteristic of postural tremor measured by the 3-axis accelerometer and 3-axis gyroscope chip (Motion Tracking sensor MPU-6050) - lower value, lower tremor.	Pre-assessment (baseline testing), Post-assessment (immediately in a week following the last procedure)
Power of the signal in band from f1 to f2 (Pf1-f2)	The spectral characteristic of postural tremor measured by the 3-axis accelerometer and 3-axis gyroscope chip (Motion Tracking sensor MPU-6050) - lower value, lower tremor.	Pre-assessment (baseline testing), Post-assessment (immediately in a week following the last procedure)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Multiple Sclerosis Impact Scale (MSIS-29) - change pre/post intervention	A 29-item self-report measure with 20 items associated with a physical scale and 9 items with a psychological scale. Items ask about the impact of MS on a day-to-day life in the past two weeks. All items have 5 response options: 1 "not at all" to 5" extremely". Each of the two scales is scored by summing the responses across items, then converting to a 0-100 scale where 100 indicates the greater impact of the disease on daily function (worse health).	Pre-assessment (baseline testing), Post-assessment (immediately in a week following the last procedure)
EQ-5D-3L-health questionnaire - change pre/post intervention	Descriptive system for health-related quality of life states in adults, consisting of five dimensions (Mobility, Self-care, Usual activities, Pain & discomfort, Anxiety & depression), each of which has three severity levels that are described by statements appropriate to that dimension. A higher number means a worse quality of life.	Pre-assessment (baseline testing), Post-assessment (immediately in a week following the last procedure)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Functional Magnetic Resonance	The fMRI examinations shall be performed in the MR system Siemens Vida 3T located in IKEM using a 64-channel RF head coil. Examination protocol will include essential structural imaging (3D SPACE FLAIR sequence with an isotropic spatial resolution of 1 mm3), measurement of functional connectivity using resting-state fMRI, and measurement of structural connectivity utilising the evaluation of the spatial distribution of molecular diffusion (generalised DTI - diffusion tensor imaging, with 108 spatial directions and 3b-factors allowing the reconstruction not only of fractional anisotropy but also the diffusion kurtosis imaging). The resting of 30 seconds will be followed by a 30-second unilateral hand active movement-driven stimulation interval, repeated eight times.	Pre-assessment (baseline testing), Post-assessment (immediately in a week following the last procedure)]
Biomarkers from peripheral blood: lncRNA and dendritic cell activation	The study will include an analysis of long non-coding RNA (lncRNA), the subtypes, and the activation of dendritic cells. The dynamic of the studied parameters might bring essential knowledge on the biological effect of rehabilitation intervention in people with multiple sclerosis. These parameters will be studied and correlated concerning individual MS treatment.	Pre-assessment (baseline testing), Post-assessment (immediately in a week following the last procedure)]
Brief ICF core set for Multiple Sclerosis	For more systematic patient population characteristics and monitoring of individual levels of functioning, disability and health, we will obtain information from the Brief ICF core set for Multiple Sclerosis, the official core set by the ICF Research Branch.	Pre-assessment (baseline testing), Post-assessment (immediately in a week following the last procedure)]

Collaborators and Investigators

• Sponsor: Charles University, Czech Republic
• Investigators: Study Director: Kamila Rasova, as.prof.Dr., Clinic of rheumatology and rehabilitation,Third medical faculty CU and Faculty Thomayer Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2021
• Primary Completion (ANTICIPATED): April 1, 2025
• Study Completion (ANTICIPATED): July 1, 2025

Study Registration Dates

• First Submitted: March 16, 2021
• First Submitted That Met QC Criteria: March 18, 2021
• First Posted (ACTUAL): March 19, 2021

Study Record Updates

• Last Update Posted (ACTUAL): February 10, 2023
• Last Update Submitted That Met QC Criteria: February 9, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: multiple sclerosis; virtual reality; physical therapy; postural control; coordination; functional recovery; postural stability; hand dexterity; neuroproprioceptive "facilitation, inhibition"; Autoimmune Diseases of the Nervous System; upper limb fine motor skills; motor programme activating therapy; Demyelinating Autoimmune Disease
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis
• Other Study ID Numbers: 1983/21+4772/21 (G-21-02)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

All data sharing terms and conditions and the nature of the relationship between the study and new user will be contained in a Data-sharing Agreement that will be issued and sighed before any data are handed out. The de-identification process for each patient is to ensure anonymization of individual patient's data, in order to be able to share IPD within the terms of participant's consent and ethics committee approval.

The study policy on sharing defines the terms of privileged use by the study team. The research team requires to be appropriately notified and acknowledged in publications and other outputs of the transferred data (or analyses conducted by the study on the new users' behalf). The Data-sharing agreement will comprehend arrangements for data destruction or secure archiving.

It is planned that the data will be placed into an online repository (to be specified later).

• IPD Sharing Time Frame: The IPD will be made available from 3-months months following the first publication of findings based on the data until 3 years following the first publication.
• IPD Sharing Access Criteria: The datasets will be prepared and might be reachable on a request. The study team formally reviews access requests for proposals. The data on an exclusive basis will be made available for third party use/ the new user, which can range from direct provision of data, data analysis collaboration, and/or scientific collaboration. Also, the requester is to state the purpose for which the data are to be used.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No