Power Training in Older Multiple Sclerosis Patients (POTOMS)

The study seeks to investigate whether 24 weeks of power training has neuroprotective effects in older PwMS. Additional purposes are to examine the effects of 24 weeks power training on physical function, cognitive function and neuromuscular function. Further, it is investigated whether the potential effects of power training are maintained after 24 weeks of follow-up.

Study Overview

• Status: Recruiting
• Conditions: Multiple Sclerosis; Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Aging; Healthy Aging
• Intervention / Treatment: Other: Power training

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.

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Tobias Gaemelke, MSc; Phone Number: +45 28264508; Email: gaemelke@ph.au.dk

Study Locations

• Denmark
  • Aarhus C, Denmark, 8000
    • Recruiting
    • Tobias Gæmelke
    • Contact: Tobias K. Gaemelke, Msc; Phone Number: +45 28264508; Email: gaemelke@ph.au.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• ≥ 60 years of age.
• Clinically diagnosed with MS according to the McDonald criteria (48).
• Having an EDSS ≤ 6.5.
• able to transport themselves to the testing at Aarhus University and Aarhus University Hospital.
• able to transport themselves to training, if randomized to the PRP group.

Exclusion Criteria:

• having comorbidities (cardiovascular, respiratory, orthopedic, or other neurological diseases than MS) affecting PRP participation or MRI scans.
• having a pacemaker.
• having metallic implant(s) that prevents MRI scans.
• having untreated osteoporosis; t-score below -2.5 and a history of low energy facture or t-score below -3.0.
• participating in more than two sessions per week of structured PRE and have done so for the past 3 months.
• Are cognitively impaired at a level expected to prevent the participant from understanding training and testing instructions.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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 after week 8.	Other: Power training; First a brief warm up on a stationary bike and uni-lateral knee raises is completed. Power training: Involves exercises performed with 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 9-24. Progression: Week 1-4: 3 sets of 12 repetitions at a load of 14 repetitions maximum (RM) with focus on introducing resistance exercise and familiarizing participants with exercises. Week 5-8: 3 sets of 12 repetitions at a load of 14 RM the power training component. Week 9-16: 3 sets of 10 repetitions at a load of 12 RM. Week 17-24: 3 sets of 8 repetitions at a load of 10 RM Strengthening exercises: Bilateral leg-press; Bilateral plantar flexion; Bilateral knee extension; Unilateral banded dorsal flexion; Bilateral lying leg curl; Back extension; Shoulder press; Seated row; Chest press; Lat pull-down
No Intervention: Control Group Multiple Sclerosis; Habitual lifestyle including standard care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage brain volume change.	Whole brain atrophy will be measured from MRI-scans.	Baseline, after 24 weeks and after 48 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalized gray and white matter volume change.	MRI scan	Baseline, after 24 weeks and after 48 weeks.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glial fibrillary acidic protein (GFAP) change.	Resting blood sample- Marker of neurodegeneration.	Baseline, after 24 weeks and after 48 weeks.
Neurofilament light chain (NfL) change.	Resting blood sample-Marker of neurodegeneration:	Baseline, after 24 weeks and after 48 weeks.
Brain-derived neurotrophic factor (BDNF) change.	Resting blood sample-Neurotrophic factor.	Baseline, after 24 weeks and after 48 weeks.
Insulin-like growth factor-1 (IGF).	Resting blood sample-Neurotrophic factor.	Baseline, after 24 weeks and after 48 weeks.
C-reactive protein (CRP) change.	Resting blood sample-Inflammatory markers.	Baseline, after 24 weeks and after 48 weeks.
Interleukin-6 (IL-6) change.	Resting blood sample-Inflammatory markers.	Baseline, after 24 weeks and after 48 weeks.
Tumor necrosis alpha (TNF-alpha) change.	Resting blood sample-Inflammatory markers.	Baseline, after 24 weeks and after 48 weeks.
C-terminal collagen cross-links (CTX) change.	Resting blood sample- Bone turnover markers.	Baseline, after 24 weeks and after 48 weeks.
Type-1n-terminal propeptide (P1NP) change.	Resting blood sample- Bone turnover markers.	Baseline, after 24 weeks and after 48 weeks.
Bone mineral density of the femoral neck and lumbar spine change.	Dexa scan.	Baseline, after 24 weeks and after 48 weeks.
Body composition change.	Dexa scan- whole body scan.	Baseline, after 24 weeks and after 48 weeks.
Cognition change .	Selective Reminding Test (memory) and Symbol Digit Modalities Test (processing speed).	Baseline, after 24 weeks and after 48 weeks.
Nine step stair test change.	Time to climb a 9 step flight of stairs.	Baseline, after 24 weeks and after 48 weeks
Six Spot Step Test (SSST) change.	SSST is a measure of walking ability, balance and coordination. Measured as the time to complete the course.	Baseline, after 24 weeks and after 48 weeks.
Six-minute walk test (&MWT) change.	Distance covered on a 30 meter track during six minutes maximal walking. Distance covered each minute is noted.	Baseline, after 24 weeks and after 48 weeks.
Timed 25-Feet Walk Test (T25FWT) change.	Time to walk 25 feet (normal walk and maximal walk pace).	Baseline, after 24 weeks and after 48 weeks.
Short Physical performance battery change.	Composite score from Five Times Sit- to- Stand Test, Tandem Test and 3 meter walk test.	Baseline, after 24 weeks and after 48 weeks.
Grip strength change.	Measured by Hand Dynamoter.	Baseline, after 24 weeks and after 48 weeks.
SF-12 change.	Patient Reported Outcome Measure.	Baseline, after 24 weeks and after 48 weeks.
Pittsburg Sleep Qulity Index change.	Patient Reported Outcome Measure.	Baseline, after 24 weeks and after 48 weeks.
Brief pain inventory change.	Patient Reported Outcome Measure.	Baseline, after 24 weeks and after 48 weeks.
Baecke Physical Activity change.	Patient Reported Outcome Measure.	Baseline, after 24 weeks and after 48 weeks.
HADS change.	Patient Reported Outcome Measure.	Baseline, after 24 weeks and after 48 weeks.
EQ-5D change.	Patient Reported Outcome Measure.	Baseline, after 24 weeks and after 48 weeks.
FES-I change.	Patient Reported Outcome Measure.	Baseline, after 24 weeks and after 48 weeks.
Multiple Sclerosis Impact Scale (MSIS-29) change.	Patient Reported Outcome Measure (only applicable for people with MS).	Baseline, after 24 weeks and after 48 weeks .
Modified Fatigue Impact Scale (MFIS) change.	Patient Reported Outcome Measure (only applicable for people with MS).	Baseline, after 24 weeks and after 48 weeks .
12-Item MS walking Scale (MSWS-12) change.	Patient Reported Outcome Measure (only applicable for people with MS).	Baseline, after 24 weeks and after 48 weeks .
Expanded Disability Status Scale (only applicable for people with MS).	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.	Baseline, after 24 weeks and after 48 weeks.
Normalized gray and white matter volume change.	MRI scan.	Baseline, after 24 weeks and after 48 weeks.
Volume of the brain nucleis: thalamus, hippocampus, putamen, caudate, globus pallidus, corticospinal tract, cingulate gyrus, corpus callosum, cervical spinal volume, motor cortex	MRI scan.	Baseline, after 24 weeks and after 48 weeks.
Diffusivity of the brain nucleis: thalamus, hippocampus, putamen, caudate, globus pallidus, corticospinal tract, cingulate gyrus, corpus callosum, cervical spinal volume, motor cortex	DTI scan.	Baseline, after 24 weeks and after 48 weeks.
White matter fibre orientations	MKI scan.	Baseline, after 24 weeks and after 48 weeks.
Maximal Voluntary Contraction (MVC) change.	The following muscle groups are tested: Knee flexors, Knee extensors, Plantar flexor and Dorsal flexor.	Baseline, after 24 weeks and after 48 weeks.
Rate of force development (RFD) change.	The following muscle groups are tested: Knee flexors, Knee extensors, Plantar flexor and Dorsal flexor.	Baseline, after 24 weeks and after 48 weeks.
Dynamic Strength change.	The following muscle groups are tested: Knee flexors, Knee extensors, Plantar flexor and Dorsal flexor.	Baseline, after 24 weeks and after 48 weeks.
Force Steadiness change.	Unilateral leg press	Baseline, after 24 weeks and after 48 weeks.
Voluntary activation	Interpolated twitch technique applied on the quadriceps muscle	Baseline, after 24 weeks and after 48 weeks.
Electromyography (EMG)	The following muscle groups are tested: Knee flexors, Knee extensors, Plantar flexor and Dorsal flexor.	Baseline, after 24 weeks and after 48 weeks.
Nine hole peg test	Manual dexterity and upper body function	Baseline, after 24 weeks and after 48 weeks.
Physical activity	Accelerometry (7 days ware time)	Baseline, after 24 weeks and after 48 weeks.

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: University of Copenhagen; University of Southern Denmark
• Investigators: Principal Investigator: Tobias Gaemelke, Msc, Exercise Biology, Department of Public Health, Aarhus University

Publications and helpful links

General Publications

• 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.
• 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.
• Hurwitz BJ. Analysis of current multiple sclerosis registries. Neurology. 2011 Jan 4;76(1 Suppl 1):S7-13. doi: 10.1212/WNL.0b013e31820502f6.
• Hvid LG, Strotmeyer ES, Skjodt 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.
• 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.
• 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. doi: 10.1007/s00421-006-0343-1. 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. doi: 10.1053/apmr.2001.23838.
• 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. doi: 10.1093/gerona/63.1.83.

Study record dates

Study Major Dates

• Study Start (Actual): December 7, 2020
• Primary Completion (Estimated): August 28, 2024
• Study Completion (Estimated): August 28, 2024

Study Registration Dates

• First Submitted: February 5, 2021
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

• Last Update Posted (Actual): June 23, 2023
• Last Update Submitted That Met QC Criteria: June 21, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Exercise; Neuroprotection; Healthy aging
• Additional Relevant MeSH Terms: Pathologic Processes; Brain Diseases; Central Nervous System Diseases; Immune System Diseases; Leukoencephalopathies; Multiple Sclerosis; Sclerosis; Nervous System Diseases; Autoimmune Diseases; Demyelinating Diseases; Autoimmune Diseases of the Nervous System; Demyelinating Autoimmune Diseases, CNS
• Other Study ID Numbers: 4168624

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No