Progressive Multiple Sclerosis (PMS)NCT07548242
The Effects of a 12-week In-phase Bilateral Exercise Programme on the Corticospinal Plasticity in People With Progressive Multiple Sclerosis
A study testing In-Phase Bilateral Upper Limb Exercise Program in people with Progressive Multiple Sclerosis (PMS), run by Marinos Chatzikonstantinou at 1 site in Cyprus.
Trial 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). Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Progressive Multiple Sclerosis (PMS)
- What is being tested?
- In-Phase Bilateral Upper Limb Exercise Program
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteCyprus
- Study dates
- 1 Feb 2025to 23 Jun 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
Progressive Multiple Sclerosis (MS) is a chronic neurological condition characterized by gradual worsening of neurological function due to damage to the central nervous system. Individuals with progressive forms of MS often experience increasing difficulties with movement, balance, muscle strength, hand function, and cognitive performance. Although disease-modifying medications can reduce inflammatory activity, they have limited effects on the neurodegenerative processes that drive disease progression. For this reason, rehabilitation approaches that promote neuroplasticity-the brain's ability to reorganize and adapt-are considered an important complementary strategy for improving function and quality of life in people with progressive MS.
This study investigates whether a structured exercise program based on coordinated bilateral upper-limb movements can enhance corticospinal plasticity and improve clinical outcomes in people with progressive MS. The corticospinal tract is a major neural pathway responsible for voluntary movement, and damage to this pathway contributes significantly to motor impairment in MS. However, some remaining neural connections may still retain the ability to adapt through activity-dependent plasticity. The study examines whether targeted exercise can stimulate these mechanisms.
Five participants diagnosed with either primary progressive or secondary progressive MS took part in the study. The research used a single-case experimental design with a concurrent multiple baseline approach, in which each participant served as their own control. During an initial baseline period, repeated measurements were collected without intervention to establish stable reference values. The exercise intervention was then introduced at different time points for each participant.
The intervention consisted of a 12-week in-phase bilateral upper-limb exercise program performed three times per week. The training included coordinated movements of both arms performed simultaneously, such as adapted sport-related exercises, functional strengthening activities, and proprioceptive neuromuscular facilitation patterns. Sessions lasted approximately 30-60 minutes and were designed to provide a high number of repetitions while maintaining a safe intensity level.
The primary outcome of the study was corticospinal excitability, measured using transcranial magnetic stimulation (TMS). Specifically, the study evaluated the active motor threshold, a neurophysiological measure reflecting the responsiveness of motor pathways in the brain. Secondary outcomes assessed potential functional changes in walking ability, balance, manual dexterity, upper-limb strength, cognitive processing speed, fatigue, and health-related quality of life.
By combining neurophysiological measurements with clinical assessments, this study aims to determine whether coordinated bilateral exercise can induce measurable changes in brain excitability and functional performance in individuals with progressive MS. The findings may provide preliminary evidence supporting the use of targeted exercise interventions as part of comprehensive neurorehabilitation strategies for people living with progressive MS.
- Conditions
- Progressive Multiple Sclerosis (PMS)
- Being tested
- In-Phase Bilateral Upper Limb Exercise Program
- Medical subject headings
- Multiple Sclerosis, Chronic Progressive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
In-Phase Bilateral Upper Limb Exercise ProgramOther
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
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Other: In-Phase Bilateral Upper Limb Exercise Program |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (1)
Clinical Tests
Secondary outcome measures assessed potential functional and clinical changes associated with the exercise intervention. Walking ability was evaluated using the Timed 25-Foot Walk Test, in which participants walked a 25-foot distance as quickly and safely as possible and the average time of two trials was recorded, with shorter times indicating better mobility. Dynamic balance and postural control were measured using the Mini Balance Evaluation Systems Test (Mini-BEST), a 14-item clinical assessment in which higher scores reflect better balance performance. Manual dexterity was assessed using the Purdue Pegboard Test, which measures fine motor coordination by requiring participants to place small pins into holes on a pegboard using one hand, the other hand, or both hands simultaneously within a limited time. Upper-limb muscle strength was evaluated using a handheld dynamometer during maximal isometric contractions of major upper-limb muscle groups. Cognitive processing speed was asses
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Apr 2026
- Study start1 Feb 2025
- Primary completion23 Jun 2025
- Study completion23 Jun 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Progressive Multiple Sclerosis (PMS)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single Case Concurrent Multiple Baseline Design
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Marinos Chatzikonstantinou
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Marinos Chatzikonstantinou, Cyprus Institute of Neurology and Genetics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07548242
- Sponsor's protocol ID
- EEBK/ΕΠ/2022/32
- Status last verified
- Apr 2026
- First submitted
- 15 Mar 2026
- Last updated
- 23 Apr 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: exercise protocol
Study at a glance
From the registry record, last updated by the sponsor on 23 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of a 12-week In-phase Bilateral Exercise Programme on the Corticospinal Plasticity in People With Progressive Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT07548242
- Acronym / sponsor ID
- EEBK/ΕΠ/2022/32
- Conditions
- Progressive Multiple Sclerosis (PMS)
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Marinos ChatzikonstantinouUniversity, hospital or other
- Study start
- 1 Feb 2025 (actual)
- Primary completion
- 23 Jun 2025 (actual)
- Study completion
- 23 Jun 2025 (actual)
- First posted
- 23 Apr 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Progressive Multiple Sclerosis (MS) is a chronic neurological condition characterized by gradual worsening of neurological function due to damage to the central nervous system. Individuals with progressive forms of MS often experience increasing difficulties with movement, balance, muscle strength, hand function, and cognitive performance. Although disease-modifying medications can reduce inflammatory activity, they have limited effects on the neurodegenerative processes that drive disease progression. For this reason, rehabilitation approaches that promote neuroplasticity-the brain's ability to reorganize and adapt-are considered an important complementary strategy for improving function and quality of life in people with progressive MS.
This study investigates whether a structured exercise program based on coordinated bilateral upper-limb movements can enhance corticospinal plasticity and improve clinical outcomes in people with progressive MS. The corticospinal tract is a major neural pathway responsible for voluntary movement, and damage to this pathway contributes significantly to motor impairment in MS. However, some remaining neural connections may still retain the ability to adapt through activity-dependent plasticity. The study examines whether targeted exercise can stimulate these mechanisms.
Five participants diagnosed with either primary progressive or secondary progressive MS took part in the study. The research used a single-case experimental design with a concurrent multiple baseline approach, in which each participant served as their own control. During an initial baseline period, repeated measurements were collected without intervention to establish stable reference values. The exercise intervention was then introduced at different time points for each participant.
The intervention consisted of a 12-week in-phase bilateral upper-limb exercise program performed three times per week. The training included coordinated movements of both arms performed simultaneously, such as adapted sport-related exercises, functional strengthening activities, and proprioceptive neuromuscular facilitation patterns. Sessions lasted approximately 30-60 minutes and were designed to provide a high number of repetitions while maintaining a safe intensity level.
The primary outcome of the study was corticospinal excitability, measured using transcranial magnetic stimulation (TMS). Specifically, the study evaluated the active motor threshold, a neurophysiological measure reflecting the responsiveness of motor pathways in the brain. Secondary outcomes assessed potential functional changes in walking ability, balance, manual dexterity, upper-limb strength, cognitive processing speed, fatigue, and health-related quality of life.
By combining neurophysiological measurements with clinical assessments, this study aims to determine whether coordinated bilateral exercise can induce measurable changes in brain excitability and functional performance in individuals with progressive MS. The findings may provide preliminary evidence supporting the use of targeted exercise interventions as part of comprehensive neurorehabilitation strategies for people living with progressive MS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single Case Concurrent Multiple Baseline Design
| Arm | Type | Receives |
|---|---|---|
| In-Phase Bilateral Upper Limb Exercise | Experimental | Other: In-Phase Bilateral Upper Limb Exercise ProgramParticipants 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. |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (10 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| In-Phase Bilateral Upper Limb Exercise ProgramThe 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 | Other | In-Phase Bilateral Upper Limb Exercise |
Primary outcome
Active Motor Threshold
Time frame: 12 weeks
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.
1 secondary outcome
Clinical Tests
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Apr 2026.
- Individual participant dataSharing planned: Yes. exercise protocol
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing In-Phase Bilateral Upper Limb Exercise Program in people with Progressive Multiple Sclerosis (PMS), run by Marinos Chatzikonstantinou at 1 site in Cyprus.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Cyprus. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Active Motor Threshold (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Apr 2026.