Exercise and Neuroprotection in Older Persons With Multiple Sclerosis

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ClinicalTrials.gov Identifier: NCT04762342

Recruitment Status : Recruiting

First Posted : February 21, 2021

Last Update Posted : February 21, 2021

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Sponsor:

Collaborators:

University of Southern Denmark

University of Copenhagen

Information provided by (Responsible Party):

University of Aarhus

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)	Not Applicable

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

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Study Type :	Interventional (Clinical Trial)
Estimated 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 :	December 7, 2020
Estimated Primary Completion Date :	March 2024
Estimated Study Completion Date :	March 2024

Resource links provided by the National Library of Medicine

MedlinePlus Genetics related topics: Multiple sclerosis

MedlinePlus related topics: Exercise and Physical Fitness Multiple Sclerosis

U.S. FDA Resources

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. [ Time Frame: 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. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
MRI scan

Other Outcome Measures:

Hippocampus volume change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
MRI scan.
Thalamus volume change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
MRI scan.
Corpus callosum volume change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
MRI scan.
Basal Ganglia volume change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
MRI scan.
Glial fibrillary acidic protein (GFAP) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Resting blood sample- Marker of neurodegeneration.
Neurofilament light chain (NfL) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Resting blood sample-Marker of neurodegeneration:
Brain-derived neurotrophic factor (BDNF) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Resting blood sample-Neurotrophic factor.
Insulin-like growth factor-1 (IGF). [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Resting blood sample-Neurotrophic factor.
C-reactive protein (CRP) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Resting blood sample-Inflammatory markers.
Interleukin-6 (IL-6) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Resting blood sample-Inflammatory markers.
Tumor necrosis alpha (TNF-alpha) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Resting blood sample-Inflammatory markers.
C-terminal collagen cross-links (CTX) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Resting blood sample- Bone turnover markers.
Type-1n-terminal propeptide (P1NP) change. [ Time Frame: 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. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Dexa scan.
Body composition change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Dexa scan- whole body scan.
Cognition change . [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Selective Reminding Test (memory) and Symbol Digit Modalities Test (processing speed).
Nine step stair test change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks ]
Time to climb a 9 step flight of stairs.
Six Spot Step Test (SSST) change. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Time to walk 25 feet (normal walk and maximal walk pace).
Short Physical performance battery change. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: 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. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
The following muscle groups are tested: Plantor flexor and Dorsal flexor.
Interpolated Twitch Technology change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Knee extensors are tested.
Grip strength change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Measured by Hand Dynamoter.
SF-12 change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Patient Reported Outcome Measure.
Pittsburg Sleep Qulity Index change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Patient Reported Outcome Measure.
Brief pain inventory change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Patient Reported Outcome Measure.
Baecke Physical Activity change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Patient Reported Outcome Measure.
HADS change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Patient Reported Outcome Measure.
EQ-5D change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Patient Reported Outcome Measure.
FES-I change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
Patient Reported Outcome Measure.
Multiple Sclerosis Impact Scale (MSIS-29) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks . ]
Patient Reported Outcome Measure (only applicable for people with MS).
Modified Fatigue Impact Scale (MFIS) change. [ Time Frame: 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. [ Time Frame: 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). [ Time Frame: 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

Information from the National Library of Medicine

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Ages Eligible for Study:	60 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	Yes

Criteria

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)

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04762342

Contacts

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Contact: Marie-Louise K. Jørgensen, MSc	+45 22292062	mlkj@ph.au.dk

Locations

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Denmark
Exercise Biology, Department of Public Health, Aarhus University	Recruiting
Aarhus, Denmark, 8000
Contact: Marie-Louise K. Jørgensen, Msc

Sponsors and Collaborators

University of Aarhus

University of Southern Denmark

University of Copenhagen

Investigators

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Principal Investigator:	Marie-Louise K. Jørgensen, Msc	Exercise Biology, Department of Public Health, Aarhus University

More Information

Publications:

Hurwitz BJ. Analysis of current multiple sclerosis registries. Neurology. 2011 Jan 4;76(1 Suppl 1):S7-13. doi: 10.1212/WNL.0b013e31820502f6. Review.

Marrie R, Horwitz R, Cutter G, Tyry T, Campagnolo D, Vollmer T. Comorbidity, socioeconomic status and multiple sclerosis. Mult Scler. 2008 Sep;14(8):1091-8. doi: 10.1177/1352458508092263.

Hvid LG, Strotmeyer ES, Skjødt M, Magnussen LV, Andersen M, Caserotti P. Voluntary muscle activation improves with power training and is associated with changes in gait speed in mobility-limited older adults - A randomized controlled trial. Exp Gerontol. 2016 Jul;80:51-6. doi: 10.1016/j.exger.2016.03.018. Epub 2016 Apr 14.

Aagaard P, Suetta C, Caserotti P, Magnusson SP, Kjaer M. Role of the nervous system in sarcopenia and muscle atrophy with aging: strength training as a countermeasure. Scand J Med Sci Sports. 2010 Feb;20(1):49-64. doi: 10.1111/j.1600-0838.2009.01084.x. Review.

Schoenfeld BJ, Contreras B, Willardson JM, Fontana F, Tiryaki-Sonmez G. Muscle activation during low- versus high-load resistance training in well-trained men. Eur J Appl Physiol. 2014 Dec;114(12):2491-7. doi: 10.1007/s00421-014-2976-9. Epub 2014 Aug 12.

Best JR, Chiu BK, Liang Hsu C, Nagamatsu LS, Liu-Ambrose T. Long-Term Effects of Resistance Exercise Training on Cognition and Brain Volume in Older Women: Results from a Randomized Controlled Trial. J Int Neuropsychol Soc. 2015 Nov;21(10):745-56. doi: 10.1017/S1355617715000673.

Liu-Ambrose T, Nagamatsu LS, Graf P, Beattie BL, Ashe MC, Handy TC. Resistance training and executive functions: a 12-month randomized controlled trial. Arch Intern Med. 2010 Jan 25;170(2):170-8. doi: 10.1001/archinternmed.2009.494.

Reid KF, Martin KI, Doros G, Clark DJ, Hau C, Patten C, Phillips EM, Frontera WR, Fielding RA. Comparative effects of light or heavy resistance power training for improving lower extremity power and physical performance in mobility-limited older adults. J Gerontol A Biol Sci Med Sci. 2015 Mar;70(3):374-80. doi: 10.1093/gerona/glu156. Epub 2014 Sep 8.

Caserotti P, Aagaard P, Larsen JB, Puggaard L. Explosive heavy-resistance training in old and very old adults: changes in rapid muscle force, strength and power. Scand J Med Sci Sports. 2008 Dec;18(6):773-82. doi: 10.1111/j.1600-0838.2007.00732.x. Epub 2008 Jan 30.

Bottaro M, Machado SN, Nogueira W, Scales R, Veloso J. Effect of high versus low-velocity resistance training on muscular fitness and functional performance in older men. Eur J Appl Physiol. 2007 Feb;99(3):257-64. Epub 2006 Dec 5.

Earles DR, Judge JO, Gunnarsson OT. Velocity training induces power-specific adaptations in highly functioning older adults. Arch Phys Med Rehabil. 2001 Jul;82(7):872-8.

Henwood TR, Riek S, Taaffe DR. Strength versus muscle power-specific resistance training in community-dwelling older adults. J Gerontol A Biol Sci Med Sci. 2008 Jan;63(1):83-91.

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Responsible Party:	University of Aarhus
ClinicalTrials.gov Identifier:	NCT04762342
Other Study ID Numbers:	4168624
First Posted:	February 21, 2021 Key Record Dates
Last Update Posted:	February 21, 2021
Last Verified:	January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by University of Aarhus:


Multiple Sclerosis Healthy aging Exercise Neuroprotection

Additional relevant MeSH terms:

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Multiple Sclerosis Demyelinating Diseases Nervous System Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Autoimmune Diseases	Sclerosis Pathologic Processes Immune System Diseases Leukoencephalopathies Brain Diseases Central Nervous System Diseases

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