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Exercise and Neuroprotection in Older Persons With Multiple Sclerosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04762342
Recruitment Status : Recruiting
First Posted : February 21, 2021
Last Update Posted : February 21, 2021
Sponsor:
Collaborators:
University of Southern Denmark
University of Copenhagen
Information provided by (Responsible Party):
University of Aarhus

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).

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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


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



Primary Outcome Measures :
  1. 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 :
  1. Normalized gray and white matter volume change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    MRI scan


Other Outcome Measures:
  1. Hippocampus volume change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    MRI scan.

  2. Thalamus volume change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    MRI scan.

  3. Corpus callosum volume change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    MRI scan.

  4. Basal Ganglia volume change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    MRI scan.

  5. Glial fibrillary acidic protein (GFAP) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Resting blood sample- Marker of neurodegeneration.

  6. Neurofilament light chain (NfL) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Resting blood sample-Marker of neurodegeneration:

  7. Brain-derived neurotrophic factor (BDNF) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Resting blood sample-Neurotrophic factor.

  8. Insulin-like growth factor-1 (IGF). [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Resting blood sample-Neurotrophic factor.

  9. C-reactive protein (CRP) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Resting blood sample-Inflammatory markers.

  10. Interleukin-6 (IL-6) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Resting blood sample-Inflammatory markers.

  11. Tumor necrosis alpha (TNF-alpha) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Resting blood sample-Inflammatory markers.

  12. C-terminal collagen cross-links (CTX) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Resting blood sample- Bone turnover markers.

  13. Type-1n-terminal propeptide (P1NP) change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Resting blood sample- Bone turnover markers.

  14. Bone mineral density of the femoral neck and lumbar spine change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Dexa scan.

  15. Body composition change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Dexa scan- whole body scan.

  16. Cognition change . [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Selective Reminding Test (memory) and Symbol Digit Modalities Test (processing speed).

  17. Nine step stair test change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks ]
    Time to climb a 9 step flight of stairs.

  18. 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.

  19. 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.

  20. 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).

  21. 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.

  22. 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.

  23. 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.

  24. Force Steadiness change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    The following muscle groups are tested: Plantor flexor and Dorsal flexor.

  25. Interpolated Twitch Technology change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Knee extensors are tested.

  26. Grip strength change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Measured by Hand Dynamoter.

  27. SF-12 change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Patient Reported Outcome Measure.

  28. Pittsburg Sleep Qulity Index change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Patient Reported Outcome Measure.

  29. Brief pain inventory change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Patient Reported Outcome Measure.

  30. Baecke Physical Activity change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Patient Reported Outcome Measure.

  31. HADS change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Patient Reported Outcome Measure.

  32. EQ-5D change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Patient Reported Outcome Measure.

  33. FES-I change. [ Time Frame: Baseline, after 24 weeks and after 48 weeks. ]
    Patient Reported Outcome Measure.

  34. 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).

  35. 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).

  36. 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).

  37. 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.



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Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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)

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
Publications:

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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