- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05367947
In-phase Bilateral Exercises in People With Relapsing Remitting Multiple Sclerosis
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
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
-
Limassol, Cyprus
- Dimitris Sokratous
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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)
Exclusion Criteria:
- 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
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: In-phase bilateral RRMS Participants A-E
The study follows a concurrent multiple baseline design across subjects, which involves five people with RRMS as five different case studies.
|
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
|
Through study completion, an average 35 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mini Balance Evaluation Systems Test
Time Frame: Through study completion, an average 35 weeks
|
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.
|
Through study completion, an average 35 weeks
|
Six Spot Step Test
Time Frame: Through study completion, an average 35 weeks
|
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
|
Through study completion, an average 35 weeks
|
Action Research Arm Test
Time Frame: Through study completion, an average 35 weeks
|
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).
|
Through study completion, an average 35 weeks
|
Isometric Dynamometer
Time Frame: Through study completion, an average 35 weeks
|
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.
|
Through study completion, an average 35 weeks
|
Symbol Digit Modalities Test
Time Frame: Through study completion, an average 35 weeks
|
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.
|
Through study completion, an average 35 weeks
|
Modified Fatigue Impact Scale
Time Frame: Through study completion, an average 35 weeks
|
It is a short questionnaire which requires the participants to describe the effects of fatigue during the past four weeks
|
Through study completion, an average 35 weeks
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Director: Dimitris Sokratous, MS, Cyprus University of Technology
Publications and helpful links
General Publications
- Pascual-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.
- 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.
- Whitall 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.
- Smith 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.
- Neva 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.
- Kratochwill, 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.
- Lobo 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- IBEMS
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Multiple Sclerosis
-
University Hospital, Basel, SwitzerlandSwiss National Science FoundationRecruitingMultiple Sclerosis (MS) | Relapsing-remitting Multiple Sclerosis (RRMS) | Secondary-progressive Multiple Sclerosis (SPMS) | Primary Progressive Multiple Sclerosis (PPMS)Switzerland
-
University of California, Los AngelesUnknownRelapsing-remitting Multiple Sclerosis | Secondary-progressive Multiple Sclerosis | Primary-progressive Multiple SclerosisUnited States
-
BiogenCompletedMultiple Sclerosis | Relapsing-Remitting Multiple Sclerosis | Secondary Progressive Multiple Sclerosis | Multiple Sclerosis, Primary Progressive | Multiple Sclerosis, Remittent ProgressiveJapan
-
The Cleveland ClinicUniversity Hospitals Cleveland Medical CenterCompletedRelapsing-Remitting Multiple Sclerosis | Secondary Progressive Multiple Sclerosis | Progressive Relapsing Multiple SclerosisUnited States
-
Rigshospitalet, DenmarkOdense University Hospital; Aarhus University Hospital; Hvidovre University Hospital and other collaboratorsActive, not recruitingRelapsing Remitting Multiple Sclerosis | Primary Progressive Multiple Sclerosis | Secondary Progressive Multiple SclerosisDenmark
-
University of California, San FranciscoUnited States Department of DefenseRecruitingMultiple Sclerosis, Chronic Progressive | Multiple Sclerosis, Relapsing-Remitting | Multiple Sclerosis (MS) | Multiple Sclerosis Relapse | Multiple Sclerosis, Primary Progressive | Multiple Sclerosis Brain Lesion | Multiple Sclerosis BenignUnited States
-
Icahn School of Medicine at Mount SinaiColumbia University; New York Stem Cell Foundation Research InstituteCompletedClinically Isolated Syndrome | Relapsing-Remitting Multiple Sclerosis | Primary Progressive Multiple Sclerosis | Secondary Progressive Multiple SclerosisUnited States
-
Queen Mary University of LondonTakeda Pharmaceuticals International, Inc.RecruitingRelapsing Remitting Multiple Sclerosis | Primary Progressive Multiple Sclerosis | Secondary Progressive Multiple SclerosisUnited Kingdom
-
Brigham and Women's HospitalMassachusetts General HospitalRecruitingMultiple Sclerosis | Relapsing Multiple Sclerosis | Primary Progressive Multiple Sclerosis | Secondary Progressive Multiple SclerosisUnited States
-
University of MinnesotaMallinckrodtTerminatedPrimary Progressive Multiple Sclerosis | Secondary Progressive Multiple Sclerosis | Progressive Relapsing Multiple SclerosisUnited States
Clinical Trials on In-phase Bilateral Exercises of the upper limbs
-
University of Sao PauloCompleted
-
Riphah International UniversityNot yet recruitingPulmonary Arterial Hypertension (PAH)Pakistan
-
University Hospital, GrenobleRecruitingRenal Insufficiency | Arteriopathy Upper Limb | Digital PressureFrance
-
Centre Antoine LacassagneThuasneRecruitingNon-metastatic Breast CancerFrance
-
National Institute of Neurological Disorders and...CompletedRepetitive TMS (rTMS) | Sham rTMS | Bilateral rTMS | Unilateral rTMSUnited States
-
Federal University of São PauloCompletedUrinary Incontinence, StressBrazil
-
Mayuben Private ClinicCompleted
-
Grünenthal GmbHJohnson & Johnson Pharmaceutical Research & Development, L.L.C.TerminatedPain | Cancer | NeoplasmUnited States, Argentina, Chile, France, Latvia, Ukraine
-
Mayuben Private ClinicCompleted
-
Mayuben Private ClinicCompletedHealthy | Dry Needling | FootSpain