Multiple SclerosisNCT05367947
In-phase Bilateral Exercises in People With Relapsing Remitting Multiple Sclerosis
A study testing In-phase Bilateral Exercises of the upper limbs in people with Multiple Sclerosis, run by Cyprus University of Technology at 1 site in Cyprus.
Trial summary
Relapsing-remitting multiple sclerosis (RRMS) is associated with changes of the corticospinal tract integrity, which is quantified by means of corticospinal plasticity. Several factors, such as exercise and interlimb coordination can influence such corticospinal plasticity. Read more about this study
- Who is it for?
- Ages 30 to 70 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- In-phase Bilateral Exercises of the upper limbs
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteCyprus
- Study dates
- 10 Mar 2023to 13 Oct 2023
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosed with relapsing remitting multiple sclerosis
- Expanded Disability Status Scale score between three and five
- Aged between 30 and 70 years
- Relapse within 30 days
- Mini Mental State of Examination score between 24 and 30 (no cognitive impairment)
Who cannot join
- Metal implants
- History of any disease affecting the central nervous system other than multiple sclerosis
- History of cardiovascular disease
- Mental disorders
- Severe orthopedic disorders
- Pregnancy
Show all 10Show fewer
- Visual deficit
- Hearing impairments,
- Εpileptic seizures
- Spasticity level on upper or lower limbs more than 1+ (slight increase in muscle tone) according to Modified Ashworth Scale
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Investigation of In-phase Bilateral Exercise Effects on Corticospinal Plasticity in Relapsing Remitting Multiple Sclerosis: a Registered Report Single-case Concurrent Multiple Baseline Design Across Five Subjects
Relapsing-remitting multiple sclerosis (RRMS) is associated with changes of the corticospinal tract integrity, which is quantified by means of corticospinal plasticity. Several factors, such as exercise and interlimb coordination can influence such corticospinal plasticity. Previous work in healthy and in stroke participants showed that the greatest improvement of corticospinal plasticity occurred during in-phase bilateral arm exercises. Here, the investigators propose a concurrent multiple baseline design study which has the advantage to verify the cause-effect inference by the staggered duration through separate baseline phases. The proposed study includes five people with RRMS, who will follow an intervention protocol which includes in-phase bilateral movements of the upper limbs, adapted to different sports activities and to functional training. The aim of the study is to investigate the effects of in-phase bilateral exercises on corticospinal plasticity and on clinical measures, using transcranial magnetic stimulation and standardized clinical assessment. To meet quality standards, the present study has been designed and will be conducted according to the "What Works Clearinghouse" criteria for single case studies.
Read the detailed description
Relapsing-remitting multiple sclerosis (RRMS) is the most common type of multiple sclerosis characterized by periods of relapses and generating various motor symptoms. These symptoms are associated with the corticospinal tract integrity neuroplasticity. The corticospinal tract is one of the major motor descending pathways providing voluntary motor function in humans. The neuroplasticity of the corticospinal tract, as defined by changes in neuron structure or function detected either directly from measures of individual neurons or inferred from measures taken across populations of neurons, is an essential factor that predicts clinical recovery in the post-relapse stage of people with RRMS. Corticospinal plasticity can be probed using Transcranial Magnetic Stimulation (TMS) and characterized via certain TMS-specific neurophysiological measures. Corticospinal plasticity is exercise-dependent and influenced by various factors, such as aerobic exercise, resistance training, as well as interlimb coordination. Previous studies that assessed corticospinal plasticity using TMS in healthy participants and in chronic stroke survivors, reported that interlimb coordination and especially in-phase bilateral movement has the strongest effect on corticospinal plasticity.
Despite the broad literature on the effects of different types of exercises on the neuroplasticity in people with RRMS, it is unclear whether in-phase bilateral exercises can promote motor related neuroplastic changes in RRMS. In light of evidence that people with RRMS have bilateral cortical lesions, which cause bilateral changes of corticospinal tract integrity, these findings raise the question about the effects of in-phase bilateral exercises on corticospinal plasticity. Such effects would provide strong evidence about whether exercise, in particular in-phase bilateral exercise, can influence the corticospinal plasticity in RRMS.
The aim of this concurrent multiple baseline design study is to investigate the effects of in-phase bilateral exercises on corticospinal plasticity and on clinical measures using TMS and standardized clinical assessment, in five people with RRMS. The intervention protocol will last for 12 consecutive weeks (30-60 minutes /session x 3 sessions/week) and include in-phase bilateral movements of the upper limbs, adapted to different sports activities and to functional training.
To define functional relation between the intervention and the results on corticospinal plasticity (i.e., resting motor threshold, motor evoked potential amplitude, latency) and on clinical measures (i.e., balance, gait, bilateral hand dexterity and strength, cognitive function), the investigators will perform a visual analysis followed by multilevel modelling and the single case educational design specific mean difference in order to estimate the magnitude of the effect size across cases.
Visual analysis will conducted first, in order to determine whether there is a functional relationship between the intervention and the outcome measures. During the visual analysis, six features of the research design graphed data will be examined: level, trend, stability, immediacy of the effect, overlap, and consistency. Over the within-phase examination an evaluation of level, trend and stability will be examined. Level will be reported from the mean score of each dependent variable and trend will determine whether the data points are monotonically decreased or increased. Stability will be estimated based on the percentage of data points falling within 15% of the phase median, if this is higher than 80% then we assume that this criterion is met. Additionally, over the between-phase examination an evaluation of overlapping data among baseline and intervention phases, consistency of data patterns and immediacy of effect will be performed. The Percentage of Non-overlapping Data index will be used to quantify the proportion of data points in the intervention phase that do not overlap with the baseline phase and the test statistic will be calculated using the Improvement Rate Difference as an effect size index. Immediacy of the effect will be examined by comparing changes in level between the last three data points of one phase and the three first data points of the next phase. Furthermore, consistency of data patterns involves the observation of the data from all phases within the same condition, with greater consistency expressing greater causal relation. Each feature will be assessed individually and collectively across to all participants and to all phases. Consequently, if the intervention protocol is the sole determinant of improvement, the investigators expect to find indicators of improvement only at the intervention phase.
Secondly, a quantitative analysis methods will conducted so to evaluate the magnitude of the intervention effect, provided there is evidence from the visual analysis. The investigators will perform all neurophysiological and clinical assessments to each participant according to the number of data points during each phase (i.e., baseline, intervention, follow up). In order to estimate the individual-level effect sizes, three different methods will be used, as suggested by 'What Works Clearinghouse', the standardized mean difference (Cohen's d), the standardized mean difference with correction for small sample sizes (Hedges' g) and piecewise regression analysis which does not only reflect the immediate intervention effect, but also the intervention effect across time. Multilevel modelling, which is recommended by the 'What Works Clearinghouse' and the single case educational design, specific mean difference index will be used to estimate the magnitude of the effect across cases and compared to the effect obtained by the single level estimates. All tests will be two sided. Statistical analysis will be performed using the statistical software R (https://www.r-project.org/).
- Conditions
- Multiple Sclerosis
- Being tested
- In-phase Bilateral Exercises of the upper limbs
- Keywords
- transcranial magnetic stimulation, multiple sclerosis, exercise
- Medical subject headings
- Multiple Sclerosis, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
In-phase Bilateral Exercises of the upper limbsBehavioural
The intervention protocol consists of in-phase bilateral exercises for the upper limbs, which are adapted to different sport activities and to fitness functional exercises, organized in a circuit training. Specifically, each session will consist of 1-3 sets, consisting of 10-15 repetitions of 9 different exercises targeting large muscle groups of the upper limbs.
The specific exercises will include sports activities of basic technical skills of basketball (e.g., different types of passing, catching and throwing the ball) and volleyball (e.g., different types of passing and receiving the ball), whereas the fitness exercises will include shoulder rows, shoulder lateral raises, elbow flexions, elbow extensions, using resistance elastic bands, as well as exercises with the patients' own body weight (e.g., pushups, TRX).
The intervention phase for each participant will consist of 12 consecutive weeks, for 3 times per week, 30-60 minutes each session.
| Study group | Role | What they receive |
|---|---|---|
| In-phase bilateral RRMS Participants A-E | Experimental | The study follows a concurrent multiple baseline design across subjects, which involves five people with RRMS as five different case studies. Receives: Behavioral: In-phase Bilateral Exercises of the upper limbs |
What is being measured
The primary outcome is the main question the study is designed to answer.
Corticospinal Plasticity
The investigators will assess the corticospinal plasticity using single pulse Transcranial Magnetic Stimulation (TMS). Following TMS recommended guidelines concerning safety and experimental conditions, bilateral cortical excitability and bilateral central motor conduction time (CMCT) will be assessed. Using electromyography (EMG) signals, the investigators will analyze bilateral cortical excitability and bilateral CMCT to determine corticospinal plasticity. The resting motor threshold (rMT) and the Motor Evoked Potential (MEP) amplitude of Abductor Pollicis Brevis muscle will define cortical excitability, while the MEP latency will be used to calculate the CMCT. To ensure methodological consistency, the investigators will collect all data by performing the same methodological procedures for both conditions (i.e., cortical excitability and CMCT) bilaterally (one side per assessment), across participants and across all time points.
Measured: Through study completion, an average 35 weeks
Secondary outcomes (6)
Mini Balance Evaluation Systems Test
It measures dynamic balance, functional mobility, and gait in neurological patients, including people with multiple sclerosis. The specific test consists of 14 items, including four of the six segments (anticipatory postural adjustments, sensory orientation, reactive postural control and dynamic gait) from the Balance Evaluation Systems Test.
Measured: Through study completion, an average 35 weeks
Six Spot Step Test
It is a timed walking test that involves kicking over a number of targets placed along a 5m-path in which rely to some extent on vision and cognition. The Six Spot Step Test is measured in the time domain replicating a complex range of sensorimotor functions, part of which are lower limb strength, spasticity, coordination, as well as balance
Measured: Through study completion, an average 35 weeks
Action Research Arm Test
It is a 19-item observational measure used by physiotherapists and other health care professionals to examine upper limb performance (i.e., coordination, dexterity and functioning). Items covering the Action Research Arm Test are categorized into four subscales (grasp, grip, pinch and gross movement).
Measured: Through study completion, an average 35 weeks
Isometric Dynamometer
We well assess the isometric muscle force of major muscle groups with the use of a hand held dynamometer, which is used in the evaluation and rehabilitation of muscle strength. Shoulder flexors, extensors, rotators, horizontal adductors and abductors adductors and abductors, elbow flexors and extensors are the major muscle groups which will be evaluated.
Measured: Through study completion, an average 35 weeks
Symbol Digit Modalities Test
We will employ the oral form which assesses the information processing speed. During the test, the participant will be given two minutes to orally match symbols with digits as quickly as possible.
Measured: Through study completion, an average 35 weeks
Modified Fatigue Impact Scale
It is a short questionnaire which requires the participants to describe the effects of fatigue during the past four weeks
Measured: Through study completion, an average 35 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 May 2022
- Study start10 Mar 2023
- Primary completion6 Oct 2023
- Study completion13 Oct 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- The study follows a concurrent multiple baseline design across subjects, which involves five people with RRMS that will be managed as five different case studies. The specific design has the advantage to verify the cause-effect inference clearly by the staggered duration through separate baseline phases
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cyprus University of Technology
- Sponsor type
- University, hospital or other
- Collaborators
- The Cyprus Foundation for Muscular Dystrophy Research
- Responsible party
- Principal investigator, Dimitris Sokratous, Cyprus University of Technology
- Investigators
- Dimitris Sokratous, MS, Study director, Cyprus University of Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05367947
- Sponsor's protocol ID
- IBEMS
- Status last verified
- Feb 2024
- First submitted
- 27 Apr 2022
- Last updated
- 7 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Neva JL, Lakhani B, Brown KE, Wadden KP, Mang CS, Ledwell NH, Borich MR, Vavasour IM, Laule C, Traboulsee AL, MacKay AL, Boyd LA. Multiple measures of corticospinal excitability are associated with clinical features of multiple sclerosis. Behav Brain Res. 2016 Jan 15;297:187-95. doi: 10.1016/j.bbr.2015.10.015. Epub 2015 Oct 20.
PubMed 26467603Pascual-Leone A, Tarazona F, Keenan J, Tormos JM, Hamilton R, Catala MD. Transcranial magnetic stimulation and neuroplasticity. Neuropsychologia. 1999 Feb;37(2):207-17. doi: 10.1016/s0028-3932(98)00095-5.
PubMed 10080378Whitall J, Waller SM, Sorkin JD, Forrester LW, Macko RF, Hanley DF, Goldberg AP, Luft A. Bilateral and unilateral arm training improve motor function through differing neuroplastic mechanisms: a single-blinded randomized controlled trial. Neurorehabil Neural Repair. 2011 Feb;25(2):118-29. doi: 10.1177/1545968310380685. Epub 2010 Oct 7.
PubMed 20930212Smith AL, Staines WR. Cortical and behavioral adaptations in response to short-term inphase versus antiphase bimanual movement training. Exp Brain Res. 2010 Sep;205(4):465-77. doi: 10.1007/s00221-010-2381-5. Epub 2010 Aug 14.
PubMed 20711566Neva JL, Legon W, Staines WR. Primary motor cortex excitability is modulated with bimanual training. Neurosci Lett. 2012 Apr 18;514(2):147-51. doi: 10.1016/j.neulet.2012.02.075. Epub 2012 Mar 3.
PubMed 22405809Kratochwill, T. R. Hitchcock, J. Horner, R. H. Levin, J. R. Odom, S. L. Rindskopf, D. M Shadish WR. Single-Case Design Technical Documentation. Work Clear website http//ies.ed.gov/ncee/wwc/pdf/wwc_scd.pdf. 2010;(December):2010.
Zhan S, Ottenbacher KJ. Single subject research designs for disability research. Disabil Rehabil. 2001 Jan 15;23(1):1-8. doi: 10.1080/09638280150211202.
PubMed 11213316Lobo MA, Moeyaert M, Baraldi Cunha A, Babik I. Single-Case Design, Analysis, and Quality Assessment for Intervention Research. J Neurol Phys Ther. 2017 Jul;41(3):187-197. doi: 10.1097/NPT.0000000000000187.
PubMed 28628553Sokratous D, Charalambous CC, Zamba-Papanicolaou E, Michailidou K, Konstantinou N. A 12-week in-phase bilateral upper limb exercise protocol promoted neuroplastic and clinical changes in people with relapsing remitting multiple sclerosis: A registered report randomized single-case concurrent multiple baseline study. PLoS One. 2024 Oct 17;19(10):e0299611. doi: 10.1371/journal.pone.0299611. eCollection 2024.
PubMed 39418242Sokratous D, Charalambous CC, Papanicolaou EZ, Michailidou K, Konstantinou N. Investigation of in-phase bilateral exercise effects on corticospinal plasticity in relapsing remitting multiple sclerosis: A registered report single-case concurrent multiple baseline design across five subjects. PLoS One. 2023 Mar 2;18(3):e0272114. doi: 10.1371/journal.pone.0272114. eCollection 2023.
PubMed 36862693
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigation of In-phase Bilateral Exercise Effects on Corticospinal Plasticity in Relapsing Remitting Multiple Sclerosis: a Registered Report Single-case Concurrent Multiple Baseline Design Across Five Subjects
- ClinicalTrials.gov ID
- NCT05367947
- Acronym / sponsor ID
- IBEMS
- Conditions
- Multiple Sclerosis
- Keywords
- transcranial magnetic stimulation, multiple sclerosis, exercise
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Cyprus University of TechnologyUniversity, hospital or other
- Collaborators
- The Cyprus Foundation for Muscular Dystrophy Research
- Study start
- 10 Mar 2023 (actual)
- Primary completion
- 6 Oct 2023 (actual)
- Study completion
- 13 Oct 2023 (actual)
- First posted
- 10 May 2022 (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.
Relapsing-remitting multiple sclerosis (RRMS) is associated with changes of the corticospinal tract integrity, which is quantified by means of corticospinal plasticity. Several factors, such as exercise and interlimb coordination can influence such corticospinal plasticity. Previous work in healthy and in stroke participants showed that the greatest improvement of corticospinal plasticity occurred during in-phase bilateral arm exercises. Here, the investigators propose a concurrent multiple baseline design study which has the advantage to verify the cause-effect inference by the staggered duration through separate baseline phases. The proposed study includes five people with RRMS, who will follow an intervention protocol which includes in-phase bilateral movements of the upper limbs, adapted to different sports activities and to functional training. The aim of the study is to investigate the effects of in-phase bilateral exercises on corticospinal plasticity and on clinical measures, using transcranial magnetic stimulation and standardized clinical assessment. To meet quality standards, the present study has been designed and will be conducted according to the "What Works Clearinghouse" criteria for single case studies.
Detailed description
Relapsing-remitting multiple sclerosis (RRMS) is the most common type of multiple sclerosis characterized by periods of relapses and generating various motor symptoms. These symptoms are associated with the corticospinal tract integrity neuroplasticity. The corticospinal tract is one of the major motor descending pathways providing voluntary motor function in humans. The neuroplasticity of the corticospinal tract, as defined by changes in neuron structure or function detected either directly from measures of individual neurons or inferred from measures taken across populations of neurons, is an essential factor that predicts clinical recovery in the post-relapse stage of people with RRMS. Corticospinal plasticity can be probed using Transcranial Magnetic Stimulation (TMS) and characterized via certain TMS-specific neurophysiological measures. Corticospinal plasticity is exercise-dependent and influenced by various factors, such as aerobic exercise, resistance training, as well as interlimb coordination. Previous studies that assessed corticospinal plasticity using TMS in healthy participants and in chronic stroke survivors, reported that interlimb coordination and especially in-phase bilateral movement has the strongest effect on corticospinal plasticity.
Despite the broad literature on the effects of different types of exercises on the neuroplasticity in people with RRMS, it is unclear whether in-phase bilateral exercises can promote motor related neuroplastic changes in RRMS. In light of evidence that people with RRMS have bilateral cortical lesions, which cause bilateral changes of corticospinal tract integrity, these findings raise the question about the effects of in-phase bilateral exercises on corticospinal plasticity. Such effects would provide strong evidence about whether exercise, in particular in-phase bilateral exercise, can influence the corticospinal plasticity in RRMS.
The aim of this concurrent multiple baseline design study is to investigate the effects of in-phase bilateral exercises on corticospinal plasticity and on clinical measures using TMS and standardized clinical assessment, in five people with RRMS. The intervention protocol will last for 12 consecutive weeks (30-60 minutes /session x 3 sessions/week) and include in-phase bilateral movements of the upper limbs, adapted to different sports activities and to functional training.
To define functional relation between the intervention and the results on corticospinal plasticity (i.e., resting motor threshold, motor evoked potential amplitude, latency) and on clinical measures (i.e., balance, gait, bilateral hand dexterity and strength, cognitive function), the investigators will perform a visual analysis followed by multilevel modelling and the single case educational design specific mean difference in order to estimate the magnitude of the effect size across cases.
Visual analysis will conducted first, in order to determine whether there is a functional relationship between the intervention and the outcome measures. During the visual analysis, six features of the research design graphed data will be examined: level, trend, stability, immediacy of the effect, overlap, and consistency. Over the within-phase examination an evaluation of level, trend and stability will be examined. Level will be reported from the mean score of each dependent variable and trend will determine whether the data points are monotonically decreased or increased. Stability will be estimated based on the percentage of data points falling within 15% of the phase median, if this is higher than 80% then we assume that this criterion is met. Additionally, over the between-phase examination an evaluation of overlapping data among baseline and intervention phases, consistency of data patterns and immediacy of effect will be performed. The Percentage of Non-overlapping Data index will be used to quantify the proportion of data points in the intervention phase that do not overlap with the baseline phase and the test statistic will be calculated using the Improvement Rate Difference as an effect size index. Immediacy of the effect will be examined by comparing changes in level between the last three data points of one phase and the three first data points of the next phase. Furthermore, consistency of data patterns involves the observation of the data from all phases within the same condition, with greater consistency expressing greater causal relation. Each feature will be assessed individually and collectively across to all participants and to all phases. Consequently, if the intervention protocol is the sole determinant of improvement, the investigators expect to find indicators of improvement only at the intervention phase.
Secondly, a quantitative analysis methods will conducted so to evaluate the magnitude of the intervention effect, provided there is evidence from the visual analysis. The investigators will perform all neurophysiological and clinical assessments to each participant according to the number of data points during each phase (i.e., baseline, intervention, follow up). In order to estimate the individual-level effect sizes, three different methods will be used, as suggested by 'What Works Clearinghouse', the standardized mean difference (Cohen's d), the standardized mean difference with correction for small sample sizes (Hedges' g) and piecewise regression analysis which does not only reflect the immediate intervention effect, but also the intervention effect across time. Multilevel modelling, which is recommended by the 'What Works Clearinghouse' and the single case educational design, specific mean difference index will be used to estimate the magnitude of the effect across cases and compared to the effect obtained by the single level estimates. All tests will be two sided. Statistical analysis will be performed using the statistical software R (https://www.r-project.org/).
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- The study follows a concurrent multiple baseline design across subjects, which involves five people with RRMS that will be managed as five different case studies. The specific design has the advantage to verify the cause-effect inference clearly by the staggered duration through separate baseline phases
| Arm | Type | Receives |
|---|---|---|
| In-phase bilateral RRMS Participants A-E | Experimental | Behavioral: In-phase Bilateral Exercises of the upper limbsThe study follows a concurrent multiple baseline design across subjects, which involves five people with RRMS as five different case studies. |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosed with relapsing remitting multiple sclerosis
- Expanded Disability Status Scale score between three and five
- Aged between 30 and 70 years
- Relapse within 30 days
- Mini Mental State of Examination score between 24 and 30 (no cognitive impairment)
Key exclusion criteria (10 listed)
- Metal implants
- History of any disease affecting the central nervous system other than multiple sclerosis
- History of cardiovascular disease
- Mental disorders
- Severe orthopedic disorders
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 Exercises of the upper limbsThe intervention protocol consists of in-phase bilateral exercises for the upper limbs, which are adapted to different sport activities and to fitness functional exercises, organized in a circuit training. Specifically, each session will consist of 1-3 sets, consisting of 10-15 repetitions of 9 different exercises targeting large muscle groups of the upper limbs. The specific exercises will include sports activities of basic technical skills of basketball (e.g., different types of passing, catching and throwing the ball) and volleyball (e.g., different types of passing and receiving the ball), whereas the fitness exercises will include shoulder rows, shoulder lateral raises, elbow flexions, elbow extensions, using resistance elastic bands, as well as exercises with the patients' own body weight (e.g., pushups, TRX). The intervention phase for each participant will consist of 12 consecutive weeks, for 3 times per week, 30-60 minutes each session. | Behavioural | In-phase bilateral RRMS Participants A-E |
Primary outcome
Corticospinal Plasticity
Time frame: Through study completion, an average 35 weeks
The investigators will assess the corticospinal plasticity using single pulse Transcranial Magnetic Stimulation (TMS). Following TMS recommended guidelines concerning safety and experimental conditions, bilateral cortical excitability and bilateral central motor conduction time (CMCT) will be assessed. Using electromyography (EMG) signals, the investigators will analyze bilateral cortical excitability and bilateral CMCT to determine corticospinal plasticity. The resting motor threshold (rMT) and the Motor Evoked Potential (MEP) amplitude of Abductor Pollicis Brevis muscle will define cortical excitability, while the MEP latency will be used to calculate the CMCT. To ensure methodological consistency, the investigators will collect all data by performing the same methodological procedures for both conditions (i.e., cortical excitability and CMCT) bilaterally (one side per assessment), across participants and across all time points.
6 secondary outcomes
Mini Balance Evaluation Systems Test
Time frame: Through study completion, an average 35 weeks
Six Spot Step Test
Time frame: Through study completion, an average 35 weeks
Action Research Arm Test
Time frame: Through study completion, an average 35 weeks
Isometric Dynamometer
Time frame: Through study completion, an average 35 weeks
Symbol Digit Modalities Test
Time frame: Through study completion, an average 35 weeks
Modified Fatigue Impact Scale
Time frame: Through study completion, an average 35 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 7 Feb 2024.
- Background: PubMed 26467603Neva JL, Lakhani B, Brown KE, Wadden KP, Mang CS, Ledwell NH, Borich MR, Vavasour IM, Laule C, Traboulsee AL, MacKay AL, Boyd LA. Multiple measures of corticospinal excitability are associated with clinical features of multiple sclerosis. Behav Brain Res. 2016 Jan 15;297:187-95. doi: 10.1016/j.bbr.2015.10.015. Epub 2015 Oct 20.
- Background: PubMed 10080378Pascual-Leone A, Tarazona F, Keenan J, Tormos JM, Hamilton R, Catala MD. Transcranial magnetic stimulation and neuroplasticity. Neuropsychologia. 1999 Feb;37(2):207-17. doi: 10.1016/s0028-3932(98)00095-5.
- Background: PubMed 20930212Whitall J, Waller SM, Sorkin JD, Forrester LW, Macko RF, Hanley DF, Goldberg AP, Luft A. Bilateral and unilateral arm training improve motor function through differing neuroplastic mechanisms: a single-blinded randomized controlled trial. Neurorehabil Neural Repair. 2011 Feb;25(2):118-29. doi: 10.1177/1545968310380685. Epub 2010 Oct 7.
- Background: PubMed 20711566Smith AL, Staines WR. Cortical and behavioral adaptations in response to short-term inphase versus antiphase bimanual movement training. Exp Brain Res. 2010 Sep;205(4):465-77. doi: 10.1007/s00221-010-2381-5. Epub 2010 Aug 14.
- Background: PubMed 22405809Neva JL, Legon W, Staines WR. Primary motor cortex excitability is modulated with bimanual training. Neurosci Lett. 2012 Apr 18;514(2):147-51. doi: 10.1016/j.neulet.2012.02.075. Epub 2012 Mar 3.
- BackgroundKratochwill, T. R. Hitchcock, J. Horner, R. H. Levin, J. R. Odom, S. L. Rindskopf, D. M Shadish WR. Single-Case Design Technical Documentation. Work Clear website http//ies.ed.gov/ncee/wwc/pdf/wwc_scd.pdf. 2010;(December):2010.
- Background: PubMed 11213316Zhan S, Ottenbacher KJ. Single subject research designs for disability research. Disabil Rehabil. 2001 Jan 15;23(1):1-8. doi: 10.1080/09638280150211202.
- Background: PubMed 28628553Lobo MA, Moeyaert M, Baraldi Cunha A, Babik I. Single-Case Design, Analysis, and Quality Assessment for Intervention Research. J Neurol Phys Ther. 2017 Jul;41(3):187-197. doi: 10.1097/NPT.0000000000000187.
- Derived from this study: PubMed 39418242Sokratous D, Charalambous CC, Zamba-Papanicolaou E, Michailidou K, Konstantinou N. A 12-week in-phase bilateral upper limb exercise protocol promoted neuroplastic and clinical changes in people with relapsing remitting multiple sclerosis: A registered report randomized single-case concurrent multiple baseline study. PLoS One. 2024 Oct 17;19(10):e0299611. doi: 10.1371/journal.pone.0299611. eCollection 2024.
- Derived from this study: PubMed 36862693Sokratous D, Charalambous CC, Papanicolaou EZ, Michailidou K, Konstantinou N. Investigation of in-phase bilateral exercise effects on corticospinal plasticity in relapsing remitting multiple sclerosis: A registered report single-case concurrent multiple baseline design across five subjects. PLoS One. 2023 Mar 2;18(3):e0272114. doi: 10.1371/journal.pone.0272114. eCollection 2023.
- Individual participant dataSharing planned: Undecided
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Multiple Sclerosis (MS) - Relapsing-remitting
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.
Dimitris Sokratous, MS study director
Cyprus University of Technology
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 Exercises of the upper limbs in people with Multiple Sclerosis, run by Cyprus University of Technology 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 7 Feb 2024. 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?
Corticospinal Plasticity (time frame: Through study completion, an average 35 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05367947, which also lists 10 linked publications.
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 7 Feb 2024.