Improving Hand Movement and Coordination in People With Multiple Sclerosis Using Transcranial Magnetic Stimulation (TMS) and Muscle Electrostimulation (FES) To Support Manual Dexterity and Daily Function
- Conditions
- Multiple Sclerosis
- Registration Number
- NCT07098273
- Lead Sponsor
- Fondazione Don Carlo Gnocchi Onlus
- Brief Summary
The goal of this interventional study is to test whether combining transcranial magnetic stimulation (TMS) with functional electrical stimulation (FES) can improve hand and upper limb function in adults with Multiple Sclerosis (MS).
The clinical trial aims to determine the following points:
1. Whether TMS combined with FES produces greater effects compared to FES alone.
2. Changes in brain and muscle activity related to hand function after treatment.
3. Specific clinical or neurophysiological factors that predict who will benefit most from the intervention. Researchers will compare the TMS-FES group (receiving brain magnetic stimulation and muscle electrostimulation) with the FES group (receiving only muscle electrostimulation) to assess whether TMS provides additional benefits in improving upper limb function
Participants will:
* Be assigned to a group (TMS-FES group or FES group)
* Attend 15 sessions (45 minutes each, 3 times per week for 5 weeks) of task-based hand and arm exercises, during which FES, or TMS and FES, will be administered to the participant.
* Undergo assessments before, after, and 3 months after training to measure hand function, brain and muscle responses, fatigue, and daily activity performance.
- Detailed Description
Multiple sclerosis (MS) is a chronic disease of the central nervous system associated with various neurological deficits, including motor impairments that negatively affect autonomy and quality of life. Among these, a significant symptom is reduced manual dexterity, which affects approximately 75% of patients and can interfere with activities of daily living (ADLs), leading to job loss and the need for assistance. This deficit, considered an indicator of disability in progressive MS, stems from altered sensorimotor integration and damage to various neural structures.
In recent years, non-invasive brain stimulation techniques, particularly Transcranial Magnetic Stimulation (TMS), have shown potential in measuring changes in cortical excitability and improving MS symptoms. TMS is a sensitive method for detecting cortical alterations and assessing corticospinal tract function through motor evoked potentials (MEPs), which are reliable biomarkers of disease progression. Moreover, studies and meta-analyses suggest that repetitive TMS (rTMS) may have therapeutic effects on cognitive deficits, spasticity, and fatigue in MS patients. In particular, stimulation of the primary motor cortex (M1) through rTMS has been shown to improve hand movement speed, although the effect dissipates quickly-typically after about 20 minutes.
To prolong these benefits, integrating TMS with Functional Electrical Stimulation (FES) could be an effective strategy. FES stimulates muscles through external surface electrical impulses to counteract the contractile inefficiency typical of MS and may further enhance residual motor function during voluntary exercises by promoting adaptive neuroplasticity. FES is already widely used in gait rehabilitation for MS, with positive effects on muscle strength and quality of life.
However, the application of FES for hand rehabilitation remains less explored, despite recommendations in favor of its investigation.
There is an urgent therapeutic need for non-pharmacological approaches to address upper limb and hand deficits, given their disabling impact on the MS population. Recent guidelines suggest exploring FES as an adjunct to traditional rehabilitation therapy to enhance its effects and improve access to rehabilitation for patients with muscle weakness.
The investigators hypothesize that the combination of TMS and FES may increase cortical excitability, reduce fatigue, and improve motor learning, leading to more effective recovery. The proposed study will assess the feasibility of a rehabilitation protocol based on these technologies, analyzing their effects on manual dexterity and on the central and peripheral neurophysiological correlates of motor recovery.
Furthermore, the investigators aim to identify predictive biomarkers of functional recovery, with the goal of personalizing rehabilitation pathways and optimizing therapeutic interventions for MS.
In this study, 30 individuals with MS are planned to be recruited, divided into the TMS-FES experimental group and the FES group. In the TMS-FES group, the primary motor cortex hand areas will be stimulated with active repetitive TMS before motor execution, while the FES group will receive sham TMS stimulation. Both groups will receive muscular electrical stimulation to assist voluntary movements during task-oriented activities.
The training will consist of three sessions per week, each lasting 45 minutes, for a total of 15 sessions. The investigators will measure variables such as age, gender, clinical status, fatigue, health perception, TMS-based biomarkers, and upper limb muscle synergies in all participants before and after the training. The investigators will investigate long-term effects on motor control, kinematic movement, and daily functional mobility three months after the end of the training through instrumental assessments and self-administered questionnaire.
20 healthy subjects are planned to be recruited, who will serve as the normative reference for the instrumental analysis assessments. The subjects will take part in a single data collection session, during which upper limb kinematics and EMG signals will be recorded while performing instrumented tasks from the Action Research Arm Test (ARAT) used for instrumental evaluation.
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 50
- age >18;
- diagnosis of MS (according to McDonald criteria);
- stable disease course without a worsening greater than 1 point on the Expanded Disability Status Scale (EDSS) in the past 4 months;
- right-handed;
- score on the Box and Block test lower than the normative value adjusted for sex and age +2 standard deviations;
- score on the cerebellar functional system of the EDSS scale <2;
- ability to provide written informed consent.
- score on the Mini-Mental State Examination <24;
- Beck Depression Inventory-II >19;
- other neurological or orthopedic conditions that would interfere with upper limb exercises;
- contraindications to the application of TMS: history of epilepsy or non-febrile seizures; presence of metallic or electronic implants in the cranial or cervical region; presence of pacemakers or implantable defibrillators; severe uncontrolled psychiatric disorders (e.g., psychosis, mania); current or suspected pregnancy;
- contraindications to the application of FES: skin integrity issues at the site of electrode placement; implanted electronic devices.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method 9-Hole Peg Test (9HPT) Before (T0) and after (T1) the rehabilitation treatment (15 sessions of 45 minutes each, 3 times per week for 5 weeks), and at 3 months from T1 (T2). The 9-Hole Peg Test evaluates manual dexterity and fine motor function of the upper limb. The test consists in taking pegs from a container, one by one, and place them into the holes on the board, as quickly as possible, using only the hand being evaluated. Pegs then have to be removed from the holes, one by one, and be placed back into the container.
Score is given according to the number of seconds it takes for the patient to complete the test or alternatively, the number of pegs placed in 50 or 100 seconds.
- Secondary Outcome Measures
Name Time Method Box and Block Test (BBT) Before (T0) and after (T1) the rehabilitation treatment (15 sessions of 45 minutes each, 3 times per week for 5 weeks), and at 3 months from T1 (T2). The Box and Block Test (BBT) measures unilateral gross manual dexterity. The BBT goal is to move, one by one, the maximum number of blocks from one compartment of a box to another of equal size, within 60 seconds. The score is determined by counting the number of blocks carried over the partition from one compartment to the other during the one-minute trial period. Higher scores on the test indicate better gross manual dexterity
Arm Function in Multiple Sclerosis Questionnaire (AMSQ) Before (T0) and after (T1) the rehabilitation treatment (15 sessions of 45 minutes each, 3 times per week for 5 weeks), and at 3 months from T1 (T2). The Arm Function in Multiple Sclerosis Questionnaire (AMSQ) is a unidimensional 31-item questionnaire for measuring arm function in Multiple Sclerosis. Each item asks about the extent to which MS has limited the individual's ability to perform specific daily activities in the past two weeks and is rated on a scale, from 1 (not at all) to 6 (unable to perform this activity). The total score is calculated by summing the scores for all items, and higher scores indicate greater limitations.
Symbol Digit Modalities Test (SDMT) Before (T0) and after (T1) the rehabilitation treatment (15 sessions of 45 minutes each, 3 times per week for 5 weeks), and at 3 months from T1 (T2). The Symbol Digit Modalities Test (SDMT) examines processing speed and sustained attention by primarily assessing complex visual scanning and tracking. Using a reference key, the test taker has 90 seconds to pair specific numbers with given geometric figures. Responses can be written or given orally, and administration time is just five minutes for either response mode.
12-Item Short Form Survey (SF-12) Before (T0) and after (T1) the rehabilitation treatment (15 sessions of 45 minutes each, 3 times per week for 5 weeks), and at 3 months from T1 (T2). The 12-Item Short Form Survey (SF-12) is a self-reported outcome measure assessing the impact of health on an individual's everyday life. Patients fill out a 12-question survey covering physical and mental health domain, which is then scored by a clinician or researcher. The responses are scored using a standardized algorithm to calculate two summary scores: the Physical Component Summary (PCS-12) and the Mental Component Summary (MCS-12). These scores are interpreted using a norm-based scoring system, with a mean of 50 and a standard deviation of 10 in the general population. Higher scores generally indicate better health.
Intrinsic Motivation Inventory (IMI) Before (T0) and after (T1) the rehabilitation treatment (15 sessions of 45 minutes each, 3 times per week for 5 weeks), and at 3 months from T1 (T2). The Intrinsic Motivation Inventory (IMI) is a multidimensional measurement device intended to assess participants' subjective experience related to a target activity in laboratory experiments. The instrument yields six subscale scores assessing participants': interest/enjoyment, perceived competence, effort, value/usefulness, felt pressure and tension, and perceived choice while performing a given activity.
System Usability Scale (SUS) After (T1) the rehabilitation treatment (15 sessions of 45 minutes each, 3 times per week for 5 weeks). The System Usability Scale (SUS) is a well-established and reliable tool for assessing the usability of rehabilitation technologies. It consists of 10 statements that evaluate aspects such as ease of use, intuitiveness, and effectiveness. Participants rate each statement on a 5-point scale, ranging from "strongly disagree" to "strongly agree." The responses are then calculated to produce a final usability score out of 100.
Fatigue Scale of Motor and Cognitive Functions (FSMC) Before (T0) and after (T1) the rehabilitation treatment (15 sessions of 45 minutes each, 3 times per week for 5 weeks), and at 3 months from T1 (T2). The Fatigue Scale of Motor and Cognitive Functions (FSMC) is a 20-item scale developed as a measure of cognitive and motor fatigue for people with MS. The responses to the items are summed to create separate scores for motor and cognitive fatigue, as well as a total fatigue score. Higher scores generally indicate greater fatigue.
Trial Locations
- Locations (2)
Fondazione Italiana Sclerosi Multipla
🇮🇹Genova, Italy
IRCCS "Santa Maria Nascente" - Fondazione Don Gnocchi
🇮🇹Milan, Italy
Fondazione Italiana Sclerosi Multipla🇮🇹Genova, ItalyAndrea Tacchino, ProfessorPrincipal Investigator