Exercise and Neuroprotection in Older Persons With Multiple Sclerosis

Sponsor

University of Aarhus (Other)

Overall Status

Recruiting

CT.gov ID

NCT04762342

Collaborator

University of Southern Denmark (Other), University of Copenhagen (Other)

120

Enrollment

Location

Arms

38.8

Anticipated Duration (Months)

3.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The study seeks to investigate whether 24 weeks of power training has neuroprotective effects in older PwMS. Additional purposes are to examine whether older PwMS have blunted exercise adaptations, compared to age- and gender-matched healthy controls, and to investigate whether the potential effects of power training are maintained after 24 weeks of follow-up.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis Sclerosis Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases of the Nervous System Demyelinating Diseases Healthy Aging Aging	Other: Resistance training (Power training)	N/A

Detailed Description

Over the past 3-4 decades, the lifespan among people with multiple sclerosis (MS) has increased substantially. Today more than one-third of all people with MS are 60 years or older. With advanced age, people with MS are more likely to have impairments in cognitive and physical function.

Positive adaptations within the nervous system (~neuroplasticity) have been shown to occur in people with MS following periods of resistance training (RT). This resembles the observations in young and old healthy individuals. Moreover, a specific type of RT termed power training appears to be particularly beneficial, as it emphasizes an explosive concentric phase of muscle contraction. This taxes the nervous system to a very high extent. As a result, power training has been shown to improve several aspects that rely on the nervous system in older individuals without MS. These aspects include cognition, neuromuscular function, and physical function.

The investigators speculate that older people with MS would also benefit. However, no studies have looked into the effects of power training in older people with MS. Moreover, it is not known if the effects of power training are blunted, compared to healthy age- and gender-matched healthy individuals due to the marked neurodegeneration that characterizes older MS (transient/permanent damage to CNS).

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Single (Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Exercise and Neuroprotection in Older Persons With Multiple Sclerosis

Actual Study Start Date :

Dec 7, 2020

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Training Group Multiple Sclerosis 24 weeks of moderate to high-intensity power training (resistance training- emphasizing an explosive concentric phase of muscle contraction) performed twice weekly. Balance- and functional exercises are included from week 10.	Other: Resistance training (Power training) All sessions will start with a brief warm up on a stationary bike and uni-lateral knee raises. Power training: Involves exercises in which participants has to focus on performing fast/explosive muscle contraction during the concentric phase, and slow/controlled (approximately 2-3 s) muscle contraction during the eccentric phase. Functional- and balance exercises are included from week 10-24. Set, repetition, and load: Week 1-4: 3 sets of 15 repetitions at a load of 15 repetitions maximum (RM). Week 5-14: 3 sets of 12 repetitions at a load of 12 RM. Week 15-24: 3 sets of 10 repetitions at a load of 10 RM. Strengthening exercises: Bilateral leg press Bilateral plantar flexion (performed in leg press machine) Knee extension Dorsal flexion (Theraband gold resistance band (Theraband, Akron, OH, US)) Seated crunches on exercise ball (Theraband gold resistance band (Theraband, Akron, OH, US)). Seated back extension lower back
No Intervention: Control Group Multiple Sclerosis Habitual lifestyle including standard care.
Experimental: Training Group Healty Control 24 weeks of moderate to high-intensity power training (resistance training- emphasizing an explosive concentric phase of muscle contraction) performed twice weekly. Balance and functional exercises are included from week 10.	Other: Resistance training (Power training) All sessions will start with a brief warm up on a stationary bike and uni-lateral knee raises. Power training: Involves exercises in which participants has to focus on performing fast/explosive muscle contraction during the concentric phase, and slow/controlled (approximately 2-3 s) muscle contraction during the eccentric phase. Functional- and balance exercises are included from week 10-24. Set, repetition, and load: Week 1-4: 3 sets of 15 repetitions at a load of 15 repetitions maximum (RM). Week 5-14: 3 sets of 12 repetitions at a load of 12 RM. Week 15-24: 3 sets of 10 repetitions at a load of 10 RM. Strengthening exercises: Bilateral leg press Bilateral plantar flexion (performed in leg press machine) Knee extension Dorsal flexion (Theraband gold resistance band (Theraband, Akron, OH, US)) Seated crunches on exercise ball (Theraband gold resistance band (Theraband, Akron, OH, US)). Seated back extension lower back
No Intervention: Control Group Healthy Control Habitual lifestyle

Outcome Measures

Primary Outcome Measures

Percentage brain volume change. [Baseline, after 24 weeks and after 48 weeks.]
Whole brain atrophy will be measured from MRI-scans.

Secondary Outcome Measures

Normalized gray and white matter volume change. [Baseline, after 24 weeks and after 48 weeks.]
MRI scan

Other Outcome Measures

Hippocampus volume change. [Baseline, after 24 weeks and after 48 weeks.]
MRI scan.
Thalamus volume change. [Baseline, after 24 weeks and after 48 weeks.]
MRI scan.
Corpus callosum volume change. [Baseline, after 24 weeks and after 48 weeks.]
MRI scan.
Basal Ganglia volume change. [Baseline, after 24 weeks and after 48 weeks.]
MRI scan.
Glial fibrillary acidic protein (GFAP) change. [Baseline, after 24 weeks and after 48 weeks.]
Resting blood sample- Marker of neurodegeneration.
Neurofilament light chain (NfL) change. [Baseline, after 24 weeks and after 48 weeks.]
Resting blood sample-Marker of neurodegeneration:
Brain-derived neurotrophic factor (BDNF) change. [Baseline, after 24 weeks and after 48 weeks.]
Resting blood sample-Neurotrophic factor.
Insulin-like growth factor-1 (IGF). [Baseline, after 24 weeks and after 48 weeks.]
Resting blood sample-Neurotrophic factor.
C-reactive protein (CRP) change. [Baseline, after 24 weeks and after 48 weeks.]
Resting blood sample-Inflammatory markers.
Interleukin-6 (IL-6) change. [Baseline, after 24 weeks and after 48 weeks.]
Resting blood sample-Inflammatory markers.
Tumor necrosis alpha (TNF-alpha) change. [Baseline, after 24 weeks and after 48 weeks.]
Resting blood sample-Inflammatory markers.
C-terminal collagen cross-links (CTX) change. [Baseline, after 24 weeks and after 48 weeks.]
Resting blood sample- Bone turnover markers.
Type-1n-terminal propeptide (P1NP) change. [Baseline, after 24 weeks and after 48 weeks.]
Resting blood sample- Bone turnover markers.
Bone mineral density of the femoral neck and lumbar spine change. [Baseline, after 24 weeks and after 48 weeks.]
Dexa scan.
Body composition change. [Baseline, after 24 weeks and after 48 weeks.]
Dexa scan- whole body scan.
Cognition change . [Baseline, after 24 weeks and after 48 weeks.]
Selective Reminding Test (memory) and Symbol Digit Modalities Test (processing speed).
Nine step stair test change. [Baseline, after 24 weeks and after 48 weeks]
Time to climb a 9 step flight of stairs.
Six Spot Step Test (SSST) change. [Baseline, after 24 weeks and after 48 weeks.]
SSST is a measure of walking ability, balance and coordination. Measured as the time to complete the course.
Six-minute walk test (&MWT) change. [Baseline, after 24 weeks and after 48 weeks.]
Distance covered on a 30 meter track during six minutes maximal walking. Distance covered each minute is noted.
Timed 25-Feet Walk Test (T25FWT) change. [Baseline, after 24 weeks and after 48 weeks.]
Time to walk 25 feet (normal walk and maximal walk pace).
Short Physical performance battery change. [Baseline, after 24 weeks and after 48 weeks.]
Composite score from Five Times Sit- to- Stand Test, Tandem Test and 3 meter walk test.
Maximal Voluntary Contraction (MVC) change. [Baseline, after 24 weeks and after 48 weeks.]
The following muscle groups are tested: Knee flexors, Knee extensors, Plantor flexor and Dorsal flexor.
Dynamic Strength change. [Baseline, after 24 weeks and after 48 weeks.]
The following muscle groups are tested: Knee flexors, Knee extensors, Plantor flexor and Dorsal flexor.
Force Steadiness change. [Baseline, after 24 weeks and after 48 weeks.]
The following muscle groups are tested: Plantor flexor and Dorsal flexor.
Interpolated Twitch Technology change. [Baseline, after 24 weeks and after 48 weeks.]
Knee extensors are tested.
Grip strength change. [Baseline, after 24 weeks and after 48 weeks.]
Measured by Hand Dynamoter.
SF-12 change. [Baseline, after 24 weeks and after 48 weeks.]
Patient Reported Outcome Measure.
Pittsburg Sleep Qulity Index change. [Baseline, after 24 weeks and after 48 weeks.]
Patient Reported Outcome Measure.
Brief pain inventory change. [Baseline, after 24 weeks and after 48 weeks.]
Patient Reported Outcome Measure.
Baecke Physical Activity change. [Baseline, after 24 weeks and after 48 weeks.]
Patient Reported Outcome Measure.
HADS change. [Baseline, after 24 weeks and after 48 weeks.]
Patient Reported Outcome Measure.
EQ-5D change. [Baseline, after 24 weeks and after 48 weeks.]
Patient Reported Outcome Measure.
FES-I change. [Baseline, after 24 weeks and after 48 weeks.]
Patient Reported Outcome Measure.
Multiple Sclerosis Impact Scale (MSIS-29) change. [Baseline, after 24 weeks and after 48 weeks .]
Patient Reported Outcome Measure (only applicable for people with MS).
Modified Fatigue Impact Scale (MFIS) change. [Baseline, after 24 weeks and after 48 weeks .]
Patient Reported Outcome Measure (only applicable for people with MS).
12-Item MS walking Scale (MSWS-12) change. [Baseline, after 24 weeks and after 48 weeks .]
Patient Reported Outcome Measure (only applicable for people with MS).
Expanded Disability Status Scale (only applicable for people with MS). [Baseline, after 24 weeks and after 48 weeks.]
The EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability. Scoring is based on an examination by a trained exercise physiologist.

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Signed consent
Clinical MS diagnosis according to the McDonald criteria (only applicable for PwMS)
EDSS ≤6.5 (only applicable for PwMS)
Able to transport themselves to the testing sessions in Aarhus
Able to transport themselves to training, if randomized to the training group

Exclusion Criteria:

Comprise comorbidities (cardiovascular-, respiratory-, orthopedic- or other neurological diseases
Pacemaker
Metallic implant that prevents MRI scans
Participation in structured RT or power training for the past 3 months (> 1 session per week)
Cognitive impairments (The participant is not able to understand and follow training- and testing instructions)