Promoting Aerobic Training in Multiple Sclerosis

Multiple Sclerosis Clinical Trial

Official title:

Aerobic Training as Substrate for Neural Plastic Changes in Multiple Sclerosis: a Putative Disease-modifying Treatment?

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05212805
• Other study ID #: ARSEP
• Status: Recruiting
• Phase: N/A
• Start date: January 1, 2018
• Est. completion date: December 25, 2023

Study information

• Verified date: January 2022
• Source: Fondazione Italiana Sclerosi Multipla
• Contact: Giampaolo Brichetto, MD, PhD
• Phone: 0102713532
• Email: giampaolo.brichetto[@]aism.it
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Multiple sclerosis (MS) is a chronic neurological disease characterized by inflammation and degeneration within the central nervous system. Over the course of the disease, most patients with MS successively accumulate inflammatory lesions and axonal damage with an increasing degree of disability. Thus, pharmacological treatment options are currently adopted to limit inflammation and to decrease the relapse rate, or simply to alleviate symptoms. On the other hand, neurorehabilitation aims to maintain and possibly improve the residual capacities of neurological patients in order to preserve personal and social activities, constituting an important part of quality health care for MS patients. However, to date, there is no definite agreement on which specific exercise therapy program can be considered the most successful in improving activities and participation. Several studies suggest that a training based on voluntary movements produces greater improvements than a passive treatment. Aerobic exercise training has been also shown to have significant neurophysiological effects in different populations. Furtherly, sports activity may increase adherence and motivation, especially in a young population such as the MS community. However, feasibility of sports activity has not been investigated yet and, in general, the potential interest of these approaches for MS patients remains to determine.

This study aims at promoting physical activity in people with MS. Specific objectives are:

(i) to evaluate the motor behavioral and neural changes induced by aerobic exercise combined with upper limb motor training based on task-oriented exercises; (ii) to assess the feasibility of leisure time physical activity (e.g. water sports activities) largely involving upper limb function.

Participants will receive task-oriented treatment, but only the experimental group will perform also aerobic training in order to evaluate the effect of aerobic exercise. Moreover, the role of sports activities will be preliminary investigated, by promoting the participation of the included patients to local or national events focusing on adapted aerobic sports specifically involving upper limb function (e.g., water sports such as sailing, windsurfing, canoeing). Clinical measures will be performed before and after interventions.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 62
• Est. completion date: December 25, 2023
• Est. primary completion date: June 24, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Multiple sclerosis diagnosis according to McDonald criteria

• relapsing-remitting course

• absence of relapses in the last three months

• an Expanded Disability Status Score (EDSS) = 4

Exclusion Criteria:

• steroid-use, psychiatric disorders or severe cognitive impairment

• acute cardio-respiratory diseases

• magnetic resonance imaging contraindications

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Behavioral:
• Aerobic exercise
Interventions will be delivered through twenty supervised 40-minutes aerobic sessions (3 times a week). Patients will be trained on a bicycle ergometer (5-minute warm-up, 30 minute of intense training, 5-minute cool-down). Warm-up will be performed at the 30% of the maximal heart rate, while training will be performed at the 50-70% of the maximal heart rate as recommended by the general guidelines for aerobic exercise training specific for MS. Actual heart rate will be constantly monitored by a wearable heart rate monitor.
• Task-oriented upper-limb training
The training will consist in twenty 1-hour sessions (3 times a week) of exercises for neuromuscular control to improve proprioceptive sensibility, muscle strength, stability and coordination of the upper limbs, including unimanual and bimanual task-oriented exercises.
• Sport events participation
A subgroup of participants will also be involved in events promoting sports activity including both aerobic and task-oriented exercises (e.g., water sports such as sailing, windsurfing, canoeing) in order to evaluate their potential role to increase adherence to training, participation and quality of life.

Locations

Country	Name	City	State
Italy	Italian Multiple Sclerosis Association and Foundation	Genoa	GE

Sponsors (3)

Lead Sponsor	Collaborator
Fondazione Italiana Sclerosi Multipla	University Grenoble Alps, University of Genoa

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the 6 minute walk test (6mWT) performance	The 6mWT assesses distance walked over 6 minutes as a sub-maximal test of aerobic capacity/endurance	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Change in the Timed 25-Foot Walk test (T25FW) performance	The T25FW is a clinical tool that evaluates patients for quantitative mobility and leg function performance test in a timed, 25 foot walk	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Change in the Nine Hole Peg Test (NHPT) performance	The NHPT is a standardized, quantitative assessment used to measure finger dexterity	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Change in the Modified Fatigue Impact Scale (MFIS) score	The MFIS is a patient reported outcome on the effects of fatigue in terms of physical, cognitive, and psychosocial functioning (Minimum value: 0; maximum value: 84; higher scores mean a worse outcome).	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Change in the Short Form Health Survey (SF-36) score	The SF-36 is a patient reported outcome that quantifies health status and measures health-related quality of life (Minimum value: 0%; maximum value: 100%; higher scores mean a better outcome)	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Structural and functional plasticity of the Central Nervous System (CNS)	Brain structure and function will be investigated using Magnetic Resonance Imaging (MRI) and Transcranial Magnetic Stimulations (TMS) in order to detect possible changes induced by the intervention.; MRI measures: axial single-shot spin-echo echo-planar diffusion tensor imaging (DTI) to obtain DTI-derived parametric maps (in particular, fractional anisotropy, axial diffusivity, radial diffusivity and mean diffusivity) TMS measures: motor evoked potential of 1mV at rest (S1mV) in the opponens pollicis (OP) before and after paired associative stimulation (PAS), a protocol known to induce a plastic increase of the primary motor cortex (M1) excitability. PAS consists of an electric stimulus delivered on the median nerve of the right arm 25ms (PAS 25) coupled with a magnetic stimulus administered on M1 in correspondence to the OP area. Two-hundred couples of stimuli will be administered to each participants for a total duration of 14 minutes.	Baseline (T0), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Interview	Semi-structured interview deputed to explore eventual long-term effects of the intervention and effects on daily living activities and quality of life.	Up to 2 years after the intervention
Secondary	Change in the Hand Grip Strength Test (HGST) performance	HGST is a tool measuring the maximum isometric strength of the hand and forearm muscles	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Change in the Pinch Strength Test (PST) performance	PST is a tool measuring the maximum isometric strength between thumb and index	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Change in the Timed Up and Go (TUG) performance	TUG is a simple evaluative test used to measure functional mobility	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Change in the Timed Up and Go cognitive (TUG-cog) performance	TUG-cog is a simple evaluative test used to measure functional mobility during dual-task performances	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Change in the Arm Function in Multiple Sclerosis Questionnaire (AMSQ) score	The AMSQ is a patient reported outcome on upper limb functioning (Minimum value: 31; maximum value: 186; higher scores mean a worse outcome)	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Change in the 12-Item MS Walking Scale (MSWS-12) score	MSWS-12 is a self-report measure of the impact of MS on the individual's walking ability (Minimum value: 12; maximum value: 60; higher scores mean a worse outcome).	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Change in the Dual-task Impact of Daily Activities Questionnaire (DIDA-Q) score	DIDA-Q is a self-report measure of the perceived difficulties of dual-tasking (Minimum value: 0; maximum value: 76; higher scores mean a worse outcome)	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Change in the Brief Illness Perception Questionnaire (Brief IPQ) score	Brief IPQ is a self-report measure of illness perceptions (Minimum value: 0; maximum value: 70; higher scores mean a worse outcome)	Baseline (T0), after 5 days of sports activity (Ti, if applicable), after 8 weeks (T1), after 16 weeks (T2)
Secondary	Continuous monitoring of the time of activity	A tracker (smart watch or bracelet) monitors the time of activity of participants (minutes/day).	Baseline (i.e., 1 month before intervention), during sports activity (if applicable) and 1 month after intervention
Secondary	Continuous monitoring of calories expenditure	A tracker (smart watch or bracelet) monitors the calories expenditure (calories/day).	Baseline (i.e., 1 month before intervention), during sports activity (if applicable) and 1 month after intervention
Secondary	Questionnaire on acceptability	Yes/No questionnaire composed by five questions evaluating satisfaction the intervention and its organization	After 5 days of sports activity (if applicable)