Exercise Therapy in Multiple Sclerosis
Study on the Interaction Between Immune, Autonomic and Central Nervous Systems as a Target of Exercise Therapy in Multiple Sclerosis
What it found
A paper reports the results; we have not read it yet. See Papers below.
What was tested
Treatment tested
- Physical Therapy
What it measured
Main measures
Changes in clinical disability (EDSS)
Changes from baseline (time 0, t0), to the end of the 6-week exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)
Disability progressionChanges in clinical disability: Multiple Sclerosis Functional Composite (MSFC)
Changes from baseline (time 0, t0), to the end of the 6-week exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)
Disability progressionThinking and memoryWalking and mobilityChanges in visual disability
Changes from baseline (time 0, t0), to the end of the 6-week exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)
Vision
Other measures (6)
Changes in Mood-depressive trait
Changes from baseline (time 0, t0), to the end of the 6-week exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)
Mood and sleepChanges in Mood-anxiety trait
Changes from baseline (time 0, t0), to the end of the 6-week exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)
Mood and sleepNeurophysiological assessment
Changes from baseline (time 0, t0) to the end of the 6-week exercise protocol (time 1, t1)
Myelin repairNerve conduction testsChanges in autonomic function
Changes from baseline (time 0, t0) to the end of the 6-week exercise protocol (time 1, t1)
Walking and mobilityChanges in T cell function
Changes from baseline (time 0, t0), to the end of the 6-week exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)
Immune responseElectrophysiological evaluation
Changes from baseline (time 0, t0), to the end of the 6-week exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)
Immune response
Who could take part
MS (type not specified) · 18 to 65 · EDSS 5 to 6
Show the full criteria
Inclusion criteria
* Ability to provide written informed consent to the study; * Diagnosis of MS definite according to 2010 revised McDonald's criteria (Polman et al., 2011); * Age range 18-65 (included); * EDSS range between 4,5 and 6,5 (included); * Ability to participate to the study protocol.
Exclusion criteria
* Inability to provide written informed consent to the study; * Altered blood count; * Female with a positive pregnancy test at baseline or having active pregnancy plans in the following months after the beginning of the protocol; * Contraindications to gadolinium (MRI); * Contraindications to TMS; * Patients with comorbidities for a neurological disease other than MS, included other neurodegenerative chronic diseases or chronic infections (i.e tuberculosis, infectious hepatitis, HIV/AIDS); * Unstable medical condition or infections; * Use of medications with increased risk of seizures (i.e. Fampridine, 4- Aminopyridine); * Concomitant use of drugs that may alter synaptic transmission and plasticity (cannabinoids, L-dopa, antiepileptics, nicotine, baclofen, SSRI, botulinum toxin).
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
Exercise or active rehabilitation is a non-pharmacological approach increasingly used for people with Multiple Sclerosis (MS), in support of disease-modifying therapies (DMTs), with the aim of improving the quality of life and engagement in daily activities. Exercise improves several disease outcomes, like cardiovascular and neuromuscular functions and walking abilities. However, its disease modifying potential is poorly explored. Exercise might target two relevant disease hallmarks that are interconnected, such as the dysregulated immune system and the inflammatory synaptopathy. Exercise might act through the activation of the autonomic part of the vagus nerve, which is an important modulator of both the innate and adaptive immune system, through the so-called cholinergic anti-inflammatory pathway-CAP. This study aims to address the effect of exercise in reducing peripheral inflammation that drives the synaptic pathology and neurodegeneration occurring in the brain of MS patients. Patients will undergo a therapeutic exercise program, consisting of 3 hours of treatment per day, 6 days/week for a total of 6 weeks. The treatment will include both passive and active therapeutic exercises targeted to restore or preserve muscular flexibility, motor coordination and ambulatory function. The day of recruitment (time 0) patients will undergo neurological and mood examination and blood withdrawal to analyze peripheral markers of immune function. Moreover, transcranial magnetic stimulation (TMS) will be used to measure synaptic transmission, while the heart rate variability (HRV) test will be performed to explore vagal function. The effect of exercise will be evaluated at the end of rehabilitation (after 6 weeks-time 1), on the above parameters. A follow up will be included (time 2, 8 weeks after the end of the treatment) to address long-term effects on neurologic and mood measurements as well as peripheral marker levels.
Papers
Results
Mandolesi G, Gentile A, Musella A, Fresegna D, De Vito F, Bullitta S, Sepman H, Marfia GA, Centonze D. Synaptopathy connects inflammation and neurodegeneration in multiple sclerosis. Nat Rev Neurol. 2015 Dec;11(12):711-24. doi: 10.1038/nrneurol.2015.222. Epub 2015 Nov 20.Results
Motl RW, Sandroff BM, Kwakkel G, Dalgas U, Feinstein A, Heesen C, Feys P, Thompson AJ. Exercise in patients with multiple sclerosis. Lancet Neurol. 2017 Oct;16(10):848-856. doi: 10.1016/S1474-4422(17)30281-8. Epub 2017 Sep 12.Results
Charron S, McKay KA, Tremlett H. Physical activity and disability outcomes in multiple sclerosis: A systematic review (2011-2016). Mult Scler Relat Disord. 2018 Feb;20:169-177. doi: 10.1016/j.msard.2018.01.021. Epub 2018 Feb 2.Results
Gentile A, De Vito F, Fresegna D, Rizzo FR, Bullitta S, Guadalupi L, Vanni V, Buttari F, Stampanoni Bassi M, Leuti A, Chiurchiu V, Marfia GA, Mandolesi G, Centonze D, Musella A. Peripheral T cells from multiple sclerosis patients trigger synaptotoxic alterations in central neurons. Neuropathol Appl Neurobiol. 2020 Feb;46(2):160-170. doi: 10.1111/nan.12569. Epub 2019 Jun 17.Results
Carbone F, De Rosa V, Carrieri PB, Montella S, Bruzzese D, Porcellini A, Procaccini C, La Cava A, Matarese G. Regulatory T cell proliferative potential is impaired in human autoimmune disease. Nat Med. 2014 Jan;20(1):69-74. doi: 10.1038/nm.3411. Epub 2013 Dec 8.Results
Feys P, Giovannoni G, Dijsselbloem N, Centonze D, Eelen P, Lykke Andersen S. The importance of a multi-disciplinary perspective and patient activation programmes in MS management. Mult Scler. 2016 Aug;22(2 Suppl):34-46. doi: 10.1177/1352458516650741.Results
Hedegaard CJ, Krakauer M, Bendtzen K, Sorensen PS, Sellebjerg F, Nielsen CH. The effect of beta-interferon therapy on myelin basic protein-elicited CD4+ T cell proliferation and cytokine production in multiple sclerosis. Clin Immunol. 2008 Oct;129(1):80-9. doi: 10.1016/j.clim.2008.06.007. Epub 2008 Jul 23.Results
Lanzillo R, Carbone F, Quarantelli M, Bruzzese D, Carotenuto A, De Rosa V, Colamatteo A, Micillo T, De Luca Picione C, Sacca F, De Rosa A, Moccia M, Brescia Morra V, Matarese G. Immunometabolic profiling of patients with multiple sclerosis identifies new biomarkers to predict disease activity during treatment with interferon beta-1a. Clin Immunol. 2017 Oct;183:249-253. doi: 10.1016/j.clim.2017.08.Results
La Rocca C, Carbone F, De Rosa V, Colamatteo A, Galgani M, Perna F, Lanzillo R, Brescia Morra V, Orefice G, Cerillo I, Florio C, Maniscalco GT, Salvetti M, Centonze D, Uccelli A, Longobardi S, Visconti A, Matarese G. Immunometabolic profiling of T cells from patients with relapsing-remitting multiple sclerosis reveals an impairment in glycolysis and mitochondrial respiration. Metabolism. 2017 Dec;Results
Pavlov VA, Tracey KJ. Neural regulation of immunity: molecular mechanisms and clinical translation. Nat Neurosci. 2017 Feb;20(2):156-166. doi: 10.1038/nn.4477. Epub 2017 Jan 16.
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History
Started
Feb 2020
Main results due
Dec 2023
Finished
Apr 2024