Effect of Multimodal Exercise Training in Patients With Multiple Sclerosis

Official title

Effect of Multimodal Exercise Training on Disease Activity and Functional Status in Patients With Multiple Sclerosis

Overview

The study aims to examine the effects of multimodal exercise training including aerobic, strengthening and balance exercises via face-to-face and asynchronous video-based telerehabilitation on disease activity, disability level, aerobic capacity, physical activity level, balance, fatigue level and quality of life in individuals with multiple sclerosis. Therefore, this study consists of two hypotheses. Hypotheses: H0: Multimodal exercise training has no effect on disease activity and functional status in patients with multiple sclerosis H1: Multimodal exercise training has effects on disease activity and functional status in patients with multiple sclerosis

Detailed description

Multiple sclerosis (MS) is a leading cause of disability in young adults, with symptoms varying based on lesion size, location, and disease course. These symptoms often worsen over time, significantly impacting quality of life. To manage symptoms and potentially affect disease activity, patients are often directed to exercise interventions, though the impact on disease progression is still being studied. Neuroimaging, particularly magnetic resonance imaging (MRI), is commonly used to monitor MS, but MRI does not reveal brain activation levels, which is why functional MRI is recommended for a more detailed evaluation. Exercise, both face-to-face and telerehabilitation (TR), is considered an effective treatment for MS. Studies show that TR increases patient adherence and can be as effective as in-person therapy. Our study aims to assess the effects of a multimodal exercise program combining face-to-face and TR on disease activity and functional status in patients with MS (PwMS). PwMS with an Expanded Disability Status Scale (EDSS) score of 3.0 to 5.5 will be randomly assigned to either the multimodal exercise training group (Group I) or a control group (Group II). Disease activity, disability, aerobic capacity, physical activity, balance, fatigue, and quality of life will be evaluated. Group I will participate in exercise training three days a week (one day in-person, two days TR) for 12 weeks. Group II will receive no exercise during this period and will be reassessed after 12 weeks.

Interventions

• Other Multimodal Exercise Training
  The exercise training consisting of aerobic, strengthening and balance exercises will be applied for 12 weeks/3days for 1hour. One day of the exercise training will be performed in a clinical environment with a physiotherapist, and the other 2 days of the week, participants will be asked to apply asynchronous video-based telerehabilitation over the internet in their own homes. The asynchronous video-based telerehabilitation application will be performed through an account created specifically fo
• Other Control Group
  Participants in the control group will be placed on the waiting list after all evaluation methods have been applied and will be re-evaluated at the end of 12 weeks.

Primary outcome measures

• Multiple Sclerosis Functional Composite Test (The change between the initial value and the value after 3 months will be evaluated). [Time frame: Baseline and end of weeks 12]
• Functional Magnetic Resonance Imaging (fMRI) (The change between the initial value and the value after 3 months will be evaluated). [Time frame: Baseline and end of weeks 12]
• Brain-derived neurotrophic factor (BDNF) assessment (The change between the initial value and the value after 3 months will be evaluated). [Time frame: Baseline and end of weeks 12]

Secondary outcome measures (7)

• The Expanded Disability Status Scale (EDSS) (The change between the initial value and the value after 3 months will be evaluated). [Time frame: Baseline and end of weeks 12]
• 6 Minute Walk Test (6MWT) (The change between the initial value and the value after 3 months will be evaluated). [Time frame: Baseline and end of weeks 12]
• ActiGraph wGT3X-BT (The change between the initial value and the value after 3 months will be evaluated). [Time frame: Baseline and end of weeks 12]
• The Godin Leisure-Time Exercise Questionnaire (The change between the initial value and the value after 3 months will be evaluated). [Time frame: Baseline and end of weeks 12]
• Balance Assessment (The change between the initial value and the value after 3 months will be evaluated). [Time frame: Baseline and end of weeks 12]
• Fatigue Severity Scale (The change between the initial value and the value after 3 months will be evaluated). [Time frame: Baseline and end of weeks 12]
• Multiple Sclerosis International Quality of Life Questionnaire (MusiQoL) (The change between the initial value and the value after 3 months will be evaluated). [Time frame: Baseline and end of weeks 12]

Eligibility criteria

Inclusion criteria

• Being diagnosed with multiple sclerosis by a neurologist
• Volunteering to participate in the study
• Being ambulatory
• EDSS between 3.0-5.5
• Being literate
• Having internet access
• Not having participated in a standardized physiotherapy and rehabilitation program in the last 3 months

Exclusion criteria

• Having an orthopedic problem affecting its mobility
• Having psychiatric problems, severe cognitive impairment, or epilepsy in addition to the MS diagnosis
• Blurred vision or visual impairment
• Pregnancy
• Having had an attack or received corticosteroid treatment 3 months before participating in the study
• Having a disease affecting immunological parameters (infection, cancer, etc.)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Turkey (Türkiye) · 2 centers

• Istanbul University-Cerrahpasa — Istanbul
• Istanbul University-Cerrahpasa — Istanbul

Publications

• Rocca MA, Romano F, Tedone N, Filippi M. Advanced neuroimaging techniques to explore the effects of motor and cognitive rehabilitation in multiple sclerosis. J Neurol. 2024 Jul;271(7):3806-3848. doi: 10.1007/s00415-024-12395-0. Epub 2024 May 1. PMID 38691168
• Shobeiri P, Karimi A, Momtazmanesh S, Teixeira AL, Teunissen CE, van Wegen EEH, Hirsch MA, Yekaninejad MS, Rezaei N. Exercise-induced increase in blood-based brain-derived neurotrophic factor (BDNF) in people with multiple sclerosis: A systematic review and meta-analysis of exercise intervention trials. PLoS One. 2022 Mar 3;17(3):e0264557. doi: 10.1371/journal.pone.0264557. eCollection 2022. PMID 35239684
• Briken S, Rosenkranz SC, Keminer O, Patra S, Ketels G, Heesen C, Hellweg R, Pless O, Schulz KH, Gold SM. Effects of exercise on Irisin, BDNF and IL-6 serum levels in patients with progressive multiple sclerosis. J Neuroimmunol. 2016 Oct 15;299:53-58. doi: 10.1016/j.jneuroim.2016.08.007. Epub 2016 Aug 5. PMID 27725121
• Cutter GR, Baier ML, Rudick RA, Cookfair DL, Fischer JS, Petkau J, Syndulko K, Weinshenker BG, Antel JP, Confavreux C, Ellison GW, Lublin F, Miller AE, Rao SM, Reingold S, Thompson A, Willoughby E. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain. 1999 May;122 ( Pt 5):871-82. doi: 10.1093/brain/122.5.871. PMID 10355672
• Bosma LV, Kragt JJ, Brieva L, Khaleeli Z, Montalban X, Polman CH, Thompson AJ, Tintore M, Uitdehaag BM. Progression on the Multiple Sclerosis Functional Composite in multiple sclerosis: what is the optimal cut-off for the three components? Mult Scler. 2010 Jul;16(7):862-7. doi: 10.1177/1352458510370464. Epub 2010 May 20. PMID 20488826
• Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444. PMID 6685237
• ATS Committee on Proficiency Standards for Clinical Pulmonary Function Laboratories. ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med. 2002 Jul 1;166(1):111-7. doi: 10.1164/ajrccm.166.1.at1102. No abstract available. PMID 12091180
• Polhemus A, Haag C, Sieber C, Sylvester R, Kool J, Gonzenbach R, von Wyl V. Methodological heterogeneity biases physical activity metrics derived from the Actigraph GT3X in multiple sclerosis: A rapid review and comparative study. Front Rehabil Sci. 2022 Nov 28;3:989658. doi: 10.3389/fresc.2022.989658. eCollection 2022. PMID 36518351

Identifiers

NCT: NCT06676618 · IU-C20204-161

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗