Clinical trial NCT06374108: Resistance Training and Corticospinal Excitability in Multiple Sclerosis
Official title: Effects of Supervised Progressive Resistance Training on Central Nervous System Functioning (Corticospinal Excitability) and Walking Capacity in Persons With Multiple Sclerosis
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Multiple Sclerosis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
name: University of Copenhagen
First posted: 2024-04-18
Enrollment: 54
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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 In an ongoing exploratory study (unpublished), the investigators have observed that functional CNS and PNS outcomes deteriorate with disability progression from healthy to mildly to moderately disabled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.

Eligibility criteria: Inclusion Criteria:

* Age ≥ 18 years
* MS diagnosis according to the McDonald diagnostic criteria
* Shows impairments in walking capacity
* Ability to self transport to test and exercise

Exclusion Criteria:

* 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).

Primary outcomes:
measure: MEP/Mmax ratio
timeFrame: Change from Baseline to 10 weeks
Secondary outcomes:
measure: Muscle strength
timeFrame: Change from Baseline to 10 weeks
measure: Voluntary activation I
timeFrame: Change from Baseline to 10 weeks
measure: Voluntary activation II
timeFrame: Change from Baseline to 10 weeks
measure: Force Steadiness
timeFrame: Change from Baseline to 10 weeks
measure: Rate of Force Developement
timeFrame: Change from Baseline to 10 weeks
measure: Ultrasound
timeFrame: Change from Baseline to 10 weeks
measure: Resting Motor Threshold (rMT)
timeFrame: Change from Baseline to 10 weeks
measure: Active Motor Threshold (aMT)
timeFrame: Change from Baseline to 10 weeks
measure: MEP latency (resting)
timeFrame: Change from Baseline to 10 weeks
measure: MEP latency (active)
timeFrame: Change from Baseline to 10 weeks
measure: MEP amplitude (resting)
timeFrame: Change from Baseline to 10 weeks
measure: MEP amplitude (active)
timeFrame: Change from Baseline to 10 weeks
measure: Short-interval intracortical Inhibition (SICI)
timeFrame: Change from Baseline to 10 weeks
measure: Intracortical facilitation (ICF)
timeFrame: Change from Baseline to 10 weeks
measure: Cortical Silent Period (CSP)
timeFrame: Change from Baseline to 10 weeks
measure: Central Motor Conduction Time (CMCT)
timeFrame: Change from Baseline to 10 weeks
measure: EEG-EMG coherence (0-1)
timeFrame: Change from Baseline to 10 weeks
measure: Timed 25 feet walk test (T25FWT)
timeFrame: Change from Baseline to 10 weeks
measure: 6-minute walk test (6MWT)
timeFrame: Change from Baseline to 10 weeks
measure: Six spot step test (SSST)
timeFrame: Change from Baseline to 10 weeks
measure: 5 sit-to-stand (5STS)
timeFrame: Change from Baseline to 10 weeks
measure: 9-step stair ascend (9SSA)
timeFrame: Change from Baseline to 10 weeks
measure: Patient determined disease steps (PDDS)
timeFrame: Change from Baseline to 10 weeks
measure: Multiple Sclerosis Walking Scale (MSWS)
timeFrame: Change from Baseline to 10 weeks
measure: Modified fatigue impact scale (MFIS)
timeFrame: Change from Baseline to 10 weeks
measure: MS impact scale (MSIS)
timeFrame: Change from Baseline to 10 weeks
measure: Falls-efficacy scale - international (FES-1)
timeFrame: Change from Baseline to 10 weeks
measure: The Physical Activity Enjoyment Scale (PACES)
timeFrame: Change from Baseline to 10 weeks
measure: Brief pain inventory (BPI)
timeFrame: Change from Baseline to 10 weeks
measure: Baecke physical activity
timeFrame: Change from Baseline to 10 weeks
measure: Accelerometry
timeFrame: Change from Baseline to 10 weeks
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Department of Public Health
state: Central Jutland Region
city: Copenhagen
country: Denmark
facility: Department of Nutrition, Exercise and Sports, University of Copenhagen
state: Copenhagen N
Study officials:
References: