The Effects of a 12-week In-phase Bilateral Exercise Programme on the Corticospinal Plasticity in People With Progressive Multiple Sclerosis

NCT07548242 | Completed

• 1 other identifier: EEBK/ΕΠ/2022/32
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

This study investigates whether a structured exercise program using coordinated movements of both arms can improve brain and motor function in people with Progressive Multiple Sclerosis (MS). Progressive MS is associated with gradual worsening of neurological function, including difficulties with movement, strength, balance, and cognition. Because current medications have limited effects on disease progression, rehabilitation strategies that promote brain plasticity and functional recovery are increasingly important. In this study, five individuals with Progressive Multiple Sclerosis participated in a 12-week exercise program consisting of in-phase bilateral upper-limb movements performed three times per week. Brain activity related to movement was measured using transcranial magnetic stimulation (TMS), which assessed corticospinal excitability through active motor threshold measurements. Additional clinical tests evaluated walking speed, balance, hand dexterity, muscle strength, cognitive processing speed, fatigue, and quality of life. The study used a single-case experimental design with repeated measurements during baseline and intervention phases to determine whether the exercise program produced measurable neurophysiological and functional changes.

Conditions

Progressive Multiple Sclerosis (PMS)

Outcome Measures

Primary Outcomes (1)

• Active Motor Threshold

  Active Motor Threshold (aMT) will be assessed using transcranial magnetic stimulation (TMS) over the primary motor cortex during a low-level voluntary contraction of the abductor pollicis brevis (APB) muscle. Surface electromyography (EMG) will be used to record motor evoked potentials (MEPs). The aMT is defined as the minimum stimulation intensity required to elicit motor evoked potentials with an amplitude ≥200 µV in the active muscle. The outcome will be reported as stimulation intensity expressed as a percentage of maximum stimulator output (%MSO). Lower values indicate greater corticospinal excitability.

  12 weeks

Secondary Outcomes (1)

• Clinical Tests

  12 weeks

Study Arms (1)

In-Phase Bilateral Upper Limb Exercise

EXPERIMENTAL

Participants completed a 12-week exercise program consisting of in-phase bilateral upper-limb movements performed three times per week. Each session lasted approximately 30-60 minutes and included coordinated exercises involving both arms simultaneously, such as adapted sport-related movements, functional strengthening exercises, and proprioceptive neuromuscular facilitation patterns. The training was delivered in a circuit format with multiple sets of exercises targeting major upper-limb muscle groups. Exercise intensity was monitored to remain below 75% of age-predicted maximum heart rate. The program aimed to provide high repetition movement practice to promote corticospinal plasticity and improve motor and functional outcomes in individuals with progressive multiple sclerosis.

Other: In-Phase Bilateral Upper Limb Exercise Program

Interventions

In-Phase Bilateral Upper Limb Exercise Program OTHER

The intervention consisted of a 12-week structured exercise program based on in-phase bilateral upper-limb movements, performed three times per week. During these movements, homologous muscles of both arms were activated simultaneously to promote coordinated bilateral motor activity. Each session lasted approximately 30-60 minutes and included a circuit of functional exercises, adapted sport-related movements (such as basketball chest and overhead passes), resistance exercises for finger flexion and extension, and proprioceptive neuromuscular facilitation patterns. The exercises targeted major upper-limb muscle groups and were performed with a high number of repetitions to promote activity-dependent neuroplasticity. Exercise intensity was monitored using heart rate measurements and maintained below 75% of the participant's age-predicted maximum heart rate to avoid aerobic training intensity. The program was designed to stimulate corticospinal plasticity and improve motor and functional

In-Phase Bilateral Upper Limb Exercise

Eligibility Criteria

• Age: 30 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of Primary Progressive Multiple Sclerosis (PPMS) or Secondary Progressive Multiple Sclerosis (SPMS)
• Age between 30 and 75 years
• Expanded Disability Status Scale (EDSS) score between 5 and 7
• Ability to understand study procedures and provide informed consent
• Ability to safely participate in an exercise program involving coordinated upper-limb movements

You may not qualify if:

• Presence of other neurological diseases affecting the central nervous system (e.g., Parkinson's disease, stroke)
• Metallic implants in the brain contraindicating transcranial magnetic stimulation (TMS)
• History of significant cardiovascular disease (e.g., heart failure, aneurysm)
• History of epilepsy or seizures
• Severe orthopedic disorders (e.g., recent fractures, spine surgery, severe musculoskeletal injury)
• Pregnancy during the study period
• Severe visual impairments (e.g., optic neuritis, diplopia)
• Severe hearing impairments (e.g., deafness)
• Severe spasticity greater than grade 1+ on the Modified Ashworth Scale
• Severe psychiatric disorders (e.g., schizophrenia)

Sponsors & Collaborators

• Marinos Chatzikonstantinou: lead

Study Sites (1)

Cyprus Institute of Neurology and Genetics

Nicosia, 2371, Cyprus

Location

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Master's Student/ Physiotherapist

Model Details: Single Case Concurrent Multiple Baseline Design

Study Record Dates

• First Submitted: March 15, 2026
• First Posted: April 23, 2026
• Study Start: February 1, 2025
• Primary Completion: June 23, 2025
• Study Completion: June 23, 2025
• Last Updated: April 23, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

CY (1)