Resistance Training and Corticospinal Excitability in Multiple Sclerosis
- Conditions
- Multiple Sclerosis
- Interventions
- Behavioral: Progressive resistance training
- Registration Number
- NCT06374108
- Lead Sponsor
- University of Aarhus
- Brief Summary
The goal of the present study is to investigate effects of progressive resistance training on central nervous system functioning (corticospinal excitability (CSE)) and walking capacity in persons with multiple sclerosis (pwMS). A total of 54 pwMS will be enrolled and randomized into 1 of 3 groups: high dose resistant training (RT), low dose RT, and waitlist control.
- Detailed Description
Neurodegeneration is a hallmark of multiple sclerosis (MS), affecting both structure and function of the central nervous system (CNS). Neurodegeneration is the main driver of disability progression in MS, evidenced by studies showing deleterious structural and functional CNS changes, ultimately reducing quality of life. Consequently, the interaction between the nervous system and muscular system undergoes deleterious changes causing reduced neuromuscular function (i.e., ability to develop muscle strength and power) and physical function.
The functional CNS changes have been evidenced by using the non invasive brain stimulation technique Transcranial Magnetic Stimulation, showing decreased corticospinal excitability alongside increased central motor conduction time. Moreover, functional peripheral nervous system (PNS) changes have been evidenced by nerve conduction methods, revealing decreased amplitude of compound muscle action potential and increased latency of nerve signaling. In an ongoing exploratory study (unpublished), the investigators have observed that functional CNS and PNS outcomes deteriorate with disability progression from healthy to mildly to moderately disabled people with MS (PwMS).
Exercise is beneficial from both an individual and a societal perspective, and has proven to be both safe and without any noticeable side effects in PwMS. Resistance training (RT) appears particularly effective in improving neuromuscular function (mainly muscle strength) and physical function (especially walking capacity). Whilst RT and other exercise modalities may elicit positive effects on CNS structure in PwMS, it seems to require a long-term (≥ 6 months) exposure. In contrast, CNS (and potentially PNS) function may adapt much more rapidly, despite a scarcity of studies (and with heterogeneous findings) involving PwMS. Interestingly, an exploratory exercise study (non-controlled, low sample size, 10 weeks treadmill walking intervention) assessed corticospinal excitability in PwMS, and observed substantial improvements after the intervention. Apart from this study, a major knowledge gap exists in terms of elucidating the potential beneficial effects of exercise (RT in particular) on CNS (and PNS) function. Based on evidence from healthy young individuals, substantial improvements in corticospinal excitability have been shown following 2-12 weeks of RT, supporting that RT-induced improvements in corticospinal excitability can also be seen in PwMS. Lastly, as existing exercise guidelines for PwMS fails to refer to evidence on dose-response to exercise, and a recent systematic review on exercise studies found no dose-response studies in PwMS (n=202), this aspect is also of great clinical relevance.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 54
- Age ≥ 18 years
- MS diagnosis according to the McDonald diagnostic criteria
- Shows impairments in walking capacity
- Ability to self transport to test and exercise
- Pregnancy
- Neurological or other comorbidities that affects the nervous system
- Relapse within the past 2 months
- Pacemaker or metallic implants
- Hypertension (medically unregulated)
- Participation in structured RT over the past 3 months (≥ 2 sessions/week).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description High dose resistance training Progressive resistance training 10 weeks intervention with 2.5 weekly supervised resistance training sessions (2 or 3 sessions/week for high dose resistance training; 25 sessions in total). Low dose resistance training Progressive resistance training 10 weeks intervention with 1 weekly supervised resistance training session (low dose resistance training; 10 sessions in total).
- Primary Outcome Measures
Name Time Method MEP/Mmax ratio Change from Baseline to 10 weeks Cortical excitability measured as amplitude percentage ratio between MEP (resting) and Mmax (Cmap of TA). Unit (intended): %
- Secondary Outcome Measures
Name Time Method Voluntary activation II Change from Baseline to 10 weeks EMG amplitude during MVC (plantar flexion and dorsal flexion). Unit (intended): μV
Voluntary activation I Change from Baseline to 10 weeks Assessed by Interpolated Twitch Technique (ITT) (dorsal flexion). Unit (intended): %
MEP amplitude (active) Change from Baseline to 10 weeks Peak-to-peak of averaged MEP (20 stimulations of 120% rMT). Unit (intended): mV
Ultrasound Change from Baseline to 10 weeks Measure of muscle thickness of the tibialis anterior. Unit (intended): mm
Resting Motor Threshold (rMT) Change from Baseline to 10 weeks The intensity necessary to produce a motor-evoked potential (MEP) that exceeds a defined peak-to-peak amplitude (50 μV) 50% of the time in a finite number of trials. Unit (intended): % Maximum stimulator output (MSO)
Short-interval intracortical Inhibition (SICI) Change from Baseline to 10 weeks SICI measures cortical inhibition and is a TMS protocol in which two stimuli are delivered with an interstimulus interval (ISI) of 2.5 ms. Unit (intended): the relative amplitude difference of motor evoked potentials (MEPs) (%).
Central Motor Conduction Time (CMCT) Change from Baseline to 10 weeks The time it takes for the fastest action potentials to travel from the site of cortical stimulation to the spinal motoneuron. It is calculated by subtracting the peripheral motor conduction time (PMCT) from the MEP latency or by the F-wave method. Unit (intended): ms
Six spot step test (SSST) Change from Baseline to 10 weeks Objective test that measures walking coordination and balance. Unit (intended): seconds.
Muscle strength Change from Baseline to 10 weeks Maximal voluntary contraction (MVC) is the maximal force-generating capacity (plantar flexion and dorsal flexion). Unit (intended): N
Rate of Force Developement Change from Baseline to 10 weeks This is defined as the speed at which the contractile elements of the muscle can develop force (plantar flexion and dorsal flexion). Unit (intended): N/s
MEP latency (active) Change from Baseline to 10 weeks The transmission time from stimulating the cortex to the start of the evoked potential in the EMG of the target muscle. Unit (intended): ms
Cortical Silent Period (CSP) Change from Baseline to 10 weeks The temporary interruption of electromyographic signal from a muscle following a motor-evoked potential (MEP) triggered by transcranial magnetic stimulation (TMS). Unit (intended): ms
5 sit-to-stand (5STS) Change from Baseline to 10 weeks Objective test that measures functional lower limb muscle strength and power. Unit (intended): seconds.
9-step stair ascend (9SSA) Change from Baseline to 10 weeks Objective test that measures functional lower limb muscle strength and power. Unit (intended): seconds.
Force Steadiness Change from Baseline to 10 weeks A quantitative measure of the ability to control muscle tonus (dorsal flexion). Unit (intended): root-mean-square (RMS) error (Coefficient of Variation (CV))
MEP latency (resting) Change from Baseline to 10 weeks The transmission time from stimulating the cortex to the start of the evoked potential in the EMG of the target muscle. Unit (intended): ms
MEP amplitude (resting) Change from Baseline to 10 weeks Peak-to-peak of averaged MEP (20 stimulations of 120% rMT). Unit (intended): mV
Timed 25 feet walk test (T25FWT) Change from Baseline to 10 weeks Objective test that measures walking speed. Unit (intended): seconds.
MS impact scale (MSIS) Change from Baseline to 10 weeks Questionnaire that measures the impact MS has on daily life. Unit (intended): score (29-145; 29 is better)
Active Motor Threshold (aMT) Change from Baseline to 10 weeks The intensity necessary to produce a motor-evoked potential (MEP) that exceeds a defined peak-to-peak amplitude (50 μV) 50% of the time in a finite number of trials during voluntary activation (20% of MVC). Unit (intended): % Maximum stimulator output (MSO)
6-minute walk test (6MWT) Change from Baseline to 10 weeks Objective test that measures walking endurance. Unit (intended): meters.
Multiple Sclerosis Walking Scale (MSWS) Change from Baseline to 10 weeks Questionnaire that measures quality of life. Unit (intended): score (0-100; 0 is better).
EEG-EMG coherence (0-1) Change from Baseline to 10 weeks Synchronization between brain activity (EEG) and muscle activity (EMG) over a specific frequency range. Unit (intended): ranging from 0 to 1, where 0 is no coherence and 1 is perfect coherence.
Intracortical facilitation (ICF) Change from Baseline to 10 weeks ICF measures cortical facilitation and is a TMS protocol in which two stimuli are delivered with an interstimulus interval (ISI) of 10 ms. Unit (intended): the relative amplitude reduction of motor evoked potentials (MEPs) (%).
Modified fatigue impact scale (MFIS) Change from Baseline to 10 weeks Questionnaire that measures the impact fatigue has on daily life. Unit (intended): score (0-84; 0 is better)
Brief pain inventory (BPI) Change from Baseline to 10 weeks Questionnaire that measures pain severity and pain interference. Unit (intended): No scoring algorithm, but "worst pain" or the arithmetic mean of the four severity items can be used as measures of pain severity; the arithmetic mean of the seven interference items can be used as a measure of pain interference.
Accelerometry Change from Baseline to 10 weeks Method used to measures and analyze movement and acceleration in three dimensions of a person (physical activity). Unit (intended): g (m/s\^2)
Patient determined disease steps (PDDS) Change from Baseline to 10 weeks A patient-reported measure of disability. Unit (intended): score (0-8; 0 is normal).
Falls-efficacy scale - international (FES-1) Change from Baseline to 10 weeks Questionnaire that measures concerns about falling. Unit (intended): score (16-64; 16 is better)
The Physical Activity Enjoyment Scale (PACES) Change from Baseline to 10 weeks Questionnaire that measures enjoyment for physical activity. Unit (intended): score (8-56; Higher score reflect greater level of enjoyment)
Baecke physical activity Change from Baseline to 10 weeks Questionnaire (patient-reported outcome) assessing patient-reported participation in physical activities. Unit (intended): Score range is continuous (0-xx). Higher is better.
Trial Locations
- Locations (2)
Department of Public Health
🇩🇰Aarhus, Central Jutland Region, Denmark
Department of Nutrition, Exercise and Sports, University of Copenhagen
🇩🇰Copenhagen, Copenhagen N, Denmark