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

NCT07098273 | Not Yet Recruiting DMC

• 2 other identifiers: MANTRAStim-SC2024/R-Multi/010
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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:

• 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.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis; Hand Dexterity; Technology-based Rehabilitation; Functional Electrical Stimulation; Transcranial Magnetic Stimulation

Outcome Measures

Primary Outcomes (1)

• 9-Hole Peg Test (9HPT)

  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.

  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).

Secondary Outcomes (7)

• 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).

• 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).

• 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).

• 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).

• 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).

Other Outcomes (3)

• Surface Electromyography (EMGs)

  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).

• Body Kinematics

  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).

• Motor Evoked Potential (MEP)

  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).

Study Arms (2)

TMS-FES group

EXPERIMENTAL

Before movement execution, the hand area of the primary motor cortex will be stimulated using active repetitive TMS (rTMS). Subsequently, FES will be applied to assist the subject's voluntary movements during task-oriented therapy.

Device: TMS and FES- based rehabilitation

FES group

ACTIVE COMPARATOR

Before movement execution, the hand area of the primary motor cortex will be stimulated using sham TMS. Subsequently, FES will be applied to assist the subject's voluntary movements during task-oriented therapy.

Device: FES-based rehabilitation

Interventions

TMS and FES- based rehabilitation DEVICE

Each subject will receive 15 individual sessions (45 minutes each, 3 times per week for 5 weeks) of task-based hand and arm exercises. Before movement execution, the hand area of the primary motor cortex will be stimulated using active rTMS. The rTMS protocol will use intermittent theta burst stimulation (iTBS), which delivers bursts of 3 pulses at 50 Hz every 200 ms (5 Hz) for 2 seconds, followed by 8 seconds of rest, totaling 600 pulses in \~3 minutes. The hand area will be identified as the optimal site for eliciting a motor evoked potential (MEP) in the abductor digiti minimi (ADM) muscle, contralateral to the dominant limb, with the lowest possible stimulation intensity. Subsequently, FES will be applied to assist the subject's voluntary movements during the task-oriented activities. The stimulation will be triggered based on the achievement of the electromyographic (EMG) threshold of the selected muscles.

TMS-FES group

FES-based rehabilitation DEVICE

Each subject will receive 15 individual sessions (45 minutes each, 3 times per week for 5 weeks) of task-based hand and arm exercises. Before movement execution, the TMS coil will be positioned over the hand areas of the primary motor cortex, but tilted away from the scalp so as to produce a sound similar to the real intervention, but at a low intensity, without inducing current in the cortex. FES will then be applied to assist the patient's voluntary movements during the task-oriented activities. The stimulation will be triggered based on the achievement of the electromyographic (EMG) threshold of the selected muscles.

FES group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Don Carlo Gnocchi Onlus: lead
• Fondazione Italiana Sclerosi Multipla: collaborator

Study Sites (2)

Fondazione Italiana Sclerosi Multipla

Genova, Italy, 16149, Italy

Location

IRCCS "Santa Maria Nascente" - Fondazione Don Gnocchi

Milan, Italy, 20148, Italy

Location

Related Publications (20)

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MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Study Officials

• Tiziana Lencioni, PhD

  IRCCS "Santa Maria Nascente" - Fondazione Don Gnocchi

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Tiziana Lencioni, PhD

CONTACT

00390240308547; tlencioni@dongnocchi.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Pilot, controlled, multicenter, national, non-profit experimental study with parallel arms, double-blind (evaluator and participant), without the use of drugs or medical devices.

Study Record Dates

• First Submitted: July 25, 2025
• First Posted: August 1, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): May 1, 2027
• Last Updated: August 12, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be available after publication with no end date
• Access Criteria: Request should be addressed to the principal investigator or the corresponding author of the publication.

Locations

IT (2)