Effect of Multimodal Exercise Training in Patients With Multiple Sclerosis

NCT06676618 | Recruiting

• 1 other identifier: IU-C20204-161
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Multiple Sclerosis

Keywords

Exercise; Physiotherapy; Degenerative diseases; Disease activity; Multimodal

Outcome Measures

Primary Outcomes (3)

• Multiple Sclerosis Functional Composite Test (The change between the initial value and the value after 3 months will be evaluated).

  The Multiple Sclerosis Functional Composite Test evaluates disease activity through three sections: cognitive status, and upper and lower extremity function. The Paced Auditory Serial Addition Test (PASAT) measures auditory processing speed, attention, flexibility, and calculation by having the patient add numbers presented at three-second intervals. The score is based on correct answers, with a maximum of 60 points. The Timed 25 Foot Walking Test (T25FWT) assesses lower extremity function by recording the time (in seconds) taken to walk 7.62 meters as quickly and safely as possible, with the average of two trials used for scoring. The 9-Hole Peg Test (9DPT) evaluates upper extremity function by having the patient place and remove nine pegs as quickly as possible, with scores based on the average of two trials for each hand.

  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).

  fMRI is a non-invasive method that allows the examination of central nervous system function and the identification of abnormal activation patterns and/or functional connectivity caused by diseases (Rocca et al 2024).In our study, functional MRI evaluations are planned to be performed using parallel imaging sequences with a 3 T Siemens device with a 32-channel head coil. High-resolution (1 x 1 x 1 mm isotropic) sagittal 190 slices will be obtained with a T1-weighted imaging sequence (TR/TE: 7.7/3.7 ms;, FA: 8°; FOV: 256 x 256). Functional resting state data will be taken with a single-shot echo planar imaging (EPI) sequence consisting of 35 slices of 4 mm thickness, 300 dynamic shots (TR/TE: 2230/30 ms, FA: 77°; matrix: 80x80) and will last approximately 11 minutes. Before functional acquisition, magnetic field maps will be recorded in order to correct signal distortions caused by tissue inhomogeneities in the magnetic field during the analysis phase.

  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).

  BDNF is a neurotrophin that affects the survival, growth and function of neurons in the central and peripheral nervous system, provides stabilization of synapses, and regulates synaptic function, axon and dendrite branching. In our study, Enzyme-Linked Immunosorbent Assay (ELISA) will be used to assess the BDNF levels of participants. All participants will be asked not to consume alcohol and caffeine in the last 12 hours before blood collection, not to take any anti-inflammatory drugs other than their routine treatments and not to exercise. The blood samples to be collected will be centrifuged and stored at -80 degrees in Eppendorf or Falcon tubes (15 ml) (Shobeiri et al 2022; Briken et al. 2016). After the treatments are completed, the blood taken will be analyzed by experienced technicians in the laboratory together with the blood taken before exercise training.

  Baseline and end of weeks 12

Secondary Outcomes (7)

• The Expanded Disability Status Scale (EDSS) (The change between the initial value and the value after 3 months will be evaluated).

  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).

  Baseline and end of weeks 12

• ActiGraph wGT3X-BT (The change between the initial value and the value after 3 months will be evaluated).

  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).

  Baseline and end of weeks 12

• Balance Assessment (The change between the initial value and the value after 3 months will be evaluated).

  Baseline and end of weeks 12

Study Arms (2)

Multimodal Exercise Training Group

EXPERIMENTAL

Participants in the multimodal exercise training group will be given a treatment protocol consisting of aerobic exercise and strengthening exercises in the presence of a physiotherapist for a total of 12 weeks, 3 days a week for 1 hour.

Other: Multimodal Exercise Training

Control Group

OTHER

Participants in the control group will be put on the waiting list after all assessment methods have been applied and will be re-evaluated at the end of 12 weeks.

Other: Control Group

Interventions

Multimodal Exercise Training OTHER

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 for the participant on the "www.telenororehab.com" website. The exercise program will be created according to the individual's condition and progression will be provided every 3 weeks. Patients who do not attend 3 consecutive sessions will be excluded from the study.

Multimodal Exercise Training Group

Control Group OTHER

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.

Control Group

Eligibility Criteria

• Age: 20 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.)

Sponsors & Collaborators

• Istanbul University - Cerrahpasa: lead

Study Sites (2)

Istanbul University-Cerrahpasa

Istanbul, Buyukcekmece, 34500, Turkey (Türkiye)

NOT YET RECRUITING

Istanbul University-Cerrahpasa

Istanbul, Istanbul, 34810, Turkey (Türkiye)

RECRUITING

Related Publications (12)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Weikert M, Motl RW, Suh Y, McAuley E, Wynn D. Accelerometry in persons with multiple sclerosis: measurement of physical activity or walking mobility? J Neurol Sci. 2010 Mar 15;290(1-2):6-11. doi: 10.1016/j.jns.2009.12.021. Epub 2010 Jan 8.

  PMID: 20060544 BACKGROUND

• Cattaneo D, Regola A, Meotti M. Validity of six balance disorders scales in persons with multiple sclerosis. Disabil Rehabil. 2006 Jun 30;28(12):789-95. doi: 10.1080/09638280500404289.

  PMID: 16754576 BACKGROUND

• Krupp LB, LaRocca NG, Muir-Nash J, Steinberg AD. The fatigue severity scale. Application to patients with multiple sclerosis and systemic lupus erythematosus. Arch Neurol. 1989 Oct;46(10):1121-3. doi: 10.1001/archneur.1989.00520460115022.

  PMID: 2803071 BACKGROUND

• Simeoni M, Auquier P, Fernandez O, Flachenecker P, Stecchi S, Constantinescu C, Idiman E, Boyko A, Beiske A, Vollmer T, Triantafyllou N, O'Connor P, Barak Y, Biermann L, Cristiano E, Atweh S, Patrick D, Robitail S, Ammoury N, Beresniak A, Pelletier J; MusiQol study group. Validation of the Multiple Sclerosis International Quality of Life questionnaire. Mult Scler. 2008 Mar;14(2):219-30. doi: 10.1177/1352458507080733. Epub 2007 Oct 17.

  PMID: 17942521 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Motor Activity

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Behavior

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Pelin Vural, MSc

  Istanbul University-Cerrahpasa Institute of Postgraduate Education

  PRINCIPAL INVESTIGATOR

• Yonca Zenginler Yazgan, PhD

  Istanbul University-Cerrahpasa Faculty of Health Science

  STUDY CHAIR

• Murat Kürtüncü, Prof. Dr.

  Istanbul University Istanbul Faculty of Medicine Department of Neurology

  STUDY CHAIR

Central Study Contacts

Pelin Vural, MSc

CONTACT

+905344245350; pelinvural7@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer, Physiotherapist

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: November 6, 2024
• Study Start: February 10, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2028
• Last Updated: March 17, 2026

Record last verified: 2026-03

Locations

TU (2)