Resistance Training and Corticospinal Excitability in Multiple Sclerosis (NEXIMS)

University of Aarhus

Status: Enrolling

Conditions: Multiple Sclerosis

Treatments: Behavioral: Progressive resistance training

Study type: Interventional

Funder types: Other

Identifiers

NCT06374108

Neuro_Exercise

Details and patient eligibility

About

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.

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 In an ongoing exploratory study (unpublished), the investigators have observed that functional CNS and PNS outcomes deteriorate with disability progression from healthy to mildly to moderately disabled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

Enrollment: 54 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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).

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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54 participants in 3 patient groups

High dose resistance training

Active Comparator group

Description:

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).

Treatment:

Behavioral: Progressive resistance training

Low dose resistance training

Active Comparator group

Description:

10 weeks intervention with 1 weekly supervised resistance training session (low dose resistance training; 10 sessions in total).

Treatment:

Behavioral: Progressive resistance training

Waitlist control.

No Intervention group

Description:

The waitlist control group will initially be instructed to maintain their normal daily activity during the 10 week intervention period. Hereafter, they will be offered a 10 week high dose resistance training intervention that combines supervised and home based exercise sessions .