Exercise-based Therapy for Multiple Sclerosis Patients

NCT03735524 | Unknown

• 1 other identifier: NeuromedIRCCS
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

Exercise is reported to have significant beneficial effects in Multiple Sclerosis (MS) patients, particularly with respect to cardiovascular function, aerobic capacity, muscular strength and ambulatory performance. Inflammation-mediated synaptic alterations have been measured by means of transcranial magnetic stimulation (TMS) and found to correlate with disability level in MS. Due to their plastic nature, synapses represent a good therapeutic target that is sensitive to environmental stimulation, such as physical exercise. The aim of this study is to evaluate the effect of exercise in reducing peripheral inflammation that drives the synaptic pathology and neurodegeneration occurring in the brain of MS patients. Recruited patients will be given a therapeutic exercise program, consisting of 3 hours of treatment per day, 6 days/week for 4 weeks. The program will be applied on hospitalised patients to ensure adherence to the program and reducing the risk of abandonment. The rehabilitation program will be planned by a physician specialised in physical and rehabilitation medicine and will consist of both passive and active therapeutic exercises specifically aimed at restoring or maintaining muscular flexibility, range of motion, balance, coordination of movements, postural passages and transfers, and ambulation. The day of recruitment (t0) patients will undergo radiological and neurological examination. The effect of exercise will be evaluated with respect to neurologic function, mood and neurophysiological parameters, autonomic system function, and peripheral marker levels assessed at t0 and after 4 weeks (t1). A second time point will be included (t2, 8 weeks after the end of the treatment) to address long-term effects, with analysis limited to neurologic and mood measurements and peripheral marker levels.

Conditions

Multiple Sclerosis

Keywords

exercise, synaptopathy, inflammation

Outcome Measures

Primary Outcomes (3)

• Changes in clinical disability (EDSS)

  Clinical severity will be measured by the expanded disability status scale (EDSS): the EDSS scale ranges from 0 to 10 in 0.5 unit increments that represent higher levels of disability.

  Changes from baseline (time 0, t0), 4 weeks after the end of exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)

• Changes in clinical disability: Multiple Sclerosis Functional Composite (MSFC)

  The Multiple Sclerosis Functional Composite (MSFC) is a three-part composite clinical measure. Three variables were recommended as primary measures: Timed 25-Foot walk; 9-Hole Peg Test; and Paced Auditory Serial Addition Test (PASAT-3"). The results from each of these three tests are transformed into Z-scores and averaged to yield a composite score for each patient at each time point. There are 3 components: 1. the average scores from the four trials on the 9-HPT; 2. the average scores of two 25-Foot Timed Walk trials; 3. the number correct from the PASAT-3. The scores for these three dimensions are combined to create a single score that can be used to detect change over time. This is done by creating Z-scores for each component. MSFC Score = {Zarm, average + Zleg, average + Zcognitive} / 3.0 (Where Zxxx =Z-score) Increased scores represent deterioration in the 9-HPT and the 25-Foot Timed Walk, whereas decreased scores represent deterioration in the PASAT-3.

  Changes from baseline (time 0, t0), 4 weeks after the end of exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)

• Changes in clinical disability (VA)

  The best corrected visual acuity (VA) that will performed in a well-lit room using Snellen and low-contrast letter acuity (LCLA) charts to assess clinical severity.

  Changes from baseline (time 0, t0), 4 weeks after the end of exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)

Secondary Outcomes (5)

• Changes in Mood-depressive trait

  Changes from baseline (time 0, t0) to the end of the 4-week exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)

• Changes in Mood-anxiety trait

  Changes from baseline (time 0, t0) to the end of the 4-week exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)

• Neurophysiological assessment

  Changes from baseline (time 0, t0) to the end of the 4-week exercise protocol (time 1, t1)

• Changes in autonomic function

  Changes from baseline (time 0, t0) to the end of the 4-week exercise protocol (time 1, t1)

• Changes in peripheral cytokine levels

  Changes from baseline (time 0, t0) to the end of 4 week-exercise protocol (time 1, t1) and 8 weeks after the end of exercise protocol (time 2, t2)

Study Arms (1)

Exercise

EXPERIMENTAL

Conventional rehabilitation

Other: Exercise

Interventions

Exercise OTHER

Different exercises will be adopted including: repetition of different movements for ambulation and stair climbing, repetition of crossed patterns of movements for coordination, postural reactions while standing with eyes open and closed and oscillatory boards for balance, strengthening lower limb muscles, and low-intensity and long-duration static stretching of iliopsoas, rectus femoris, hamstrings, triceps surae, and lumbar spinal muscles for muscular flexibility and range of motion. In addition, advanced robotic therapy will be used to standardize rehabilitative treatment and to obtain more objective indexes of motor function. The Lokomat exoskeleton and the Biodex stability system will be used.

Also known as: Rehabilitation

Exercise

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• Inability to provide written informed consent to the study;
• Altered blood count;
• Female with 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 neurological disease other than MS, included other neurodegenerative chronic diseases or chronic infections (i.e tubercolosis, 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, antiepiletics, nicotine, baclofen, SSRI, botulinum toxin).

Sponsors & Collaborators

• Neuromed IRCCS: lead

Study Sites (1)

IRCCS Neuromed

Pozzilli, Isernia, 86077, Italy

Location

Related Publications (14)

• 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.

  PMID: 29414293 BACKGROUND

• Compston A, Coles A. Multiple sclerosis. Lancet. 2002 Apr 6;359(9313):1221-31. doi: 10.1016/S0140-6736(02)08220-X.

  PMID: 11955556 BACKGROUND

• Dalgas U, Stenager E, Jakobsen J, Petersen T, Hansen HJ, Knudsen C, Overgaard K, Ingemann-Hansen T. Resistance training improves muscle strength and functional capacity in multiple sclerosis. Neurology. 2009 Nov 3;73(18):1478-84. doi: 10.1212/WNL.0b013e3181bf98b4.

  PMID: 19884575 BACKGROUND

• Deckx N, Wens I, Nuyts AH, Hens N, De Winter BY, Koppen G, Goossens H, Van Damme P, Berneman ZN, Eijnde BO, Cools N. 12 Weeks of Combined Endurance and Resistance Training Reduces Innate Markers of Inflammation in a Randomized Controlled Clinical Trial in Patients with Multiple Sclerosis. Mediators Inflamm. 2016;2016:6789276. doi: 10.1155/2016/6789276. Epub 2016 Jan 20.

  PMID: 26903712 BACKGROUND

• Edwards T, Pilutti LA. The effect of exercise training in adults with multiple sclerosis with severe mobility disability: A systematic review and future research directions. Mult Scler Relat Disord. 2017 Aug;16:31-39. doi: 10.1016/j.msard.2017.06.003. Epub 2017 Jun 12.

  PMID: 28755682 BACKGROUND

• Feinstein A, DeLuca J, Baune BT, Filippi M, Lassman H. Cognitive and neuropsychiatric disease manifestations in MS. Mult Scler Relat Disord. 2013 Jan;2(1):4-12. doi: 10.1016/j.msard.2012.08.001. Epub 2012 Sep 25.

  PMID: 25877449 BACKGROUND

• 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.

  PMID: 27465614 BACKGROUND

• Golzari Z, Shabkhiz F, Soudi S, Kordi MR, Hashemi SM. Combined exercise training reduces IFN-gamma and IL-17 levels in the plasma and the supernatant of peripheral blood mononuclear cells in women with multiple sclerosis. Int Immunopharmacol. 2010 Nov;10(11):1415-9. doi: 10.1016/j.intimp.2010.08.008. Epub 2010 Aug 24.

  PMID: 20797460 BACKGROUND

• 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.

  PMID: 28920890 BACKGROUND

• Rampello A, Franceschini M, Piepoli M, Antenucci R, Lenti G, Olivieri D, Chetta A. Effect of aerobic training on walking capacity and maximal exercise tolerance in patients with multiple sclerosis: a randomized crossover controlled study. Phys Ther. 2007 May;87(5):545-55. doi: 10.2522/ptj.20060085. Epub 2007 Apr 3.

  PMID: 17405806 BACKGROUND

• Schulz KH, Gold SM, Witte J, Bartsch K, Lang UE, Hellweg R, Reer R, Braumann KM, Heesen C. Impact of aerobic training on immune-endocrine parameters, neurotrophic factors, quality of life and coordinative function in multiple sclerosis. J Neurol Sci. 2004 Oct 15;225(1-2):11-8. doi: 10.1016/j.jns.2004.06.009.

  PMID: 15465080 BACKGROUND

• Sternberg Z. Promoting sympathovagal balance in multiple sclerosis; pharmacological, non-pharmacological, and surgical strategies. Autoimmun Rev. 2016 Feb;15(2):113-23. doi: 10.1016/j.autrev.2015.04.012. Epub 2015 May 3.

  PMID: 25945428 BACKGROUND

• Studer V, Rocchi C, Motta C, Lauretti B, Perugini J, Brambilla L, Pareja-Gutierrez L, Camera G, Barbieri FR, Marfia GA, Centonze D, Rossi S. Heart rate variability is differentially altered in multiple sclerosis: implications for acute, worsening and progressive disability. Mult Scler J Exp Transl Clin. 2017 Apr 5;3(2):2055217317701317. doi: 10.1177/2055217317701317. eCollection 2017 Apr-Jun.

  PMID: 28607756 BACKGROUND

• van den Berg M, Dawes H, Wade DT, Newman M, Burridge J, Izadi H, Sackley CM. Treadmill training for individuals with multiple sclerosis: a pilot randomised trial. J Neurol Neurosurg Psychiatry. 2006 Apr;77(4):531-3. doi: 10.1136/jnnp.2005.064410.

  PMID: 16543538 BACKGROUND

MeSH Terms

Conditions

Multiple Sclerosis; Motor Activity; Inflammation

Interventions

Exercise; Rehabilitation

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Behavior; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Study Officials

• Diego Centonze, MD

  IRCCS Neuromed

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Diego Centonze, MD

CONTACT

+39 3934444159; centonze@uniroma2.it

Mario Stampanoni, MD

CONTACT

+39 2460181370; mario_sb@hotmail.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 10, 2018
• First Posted: November 8, 2018
• Study Start: May 1, 2019
• Primary Completion: November 1, 2020
• Study Completion: May 1, 2021
• Last Updated: November 8, 2018

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)