Clinical Trials Logo

Clinical Trial 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.


Clinical Trial Description

Clinical manifestations of Multiple Sclerosis (MS) indicate the involvement of motor, sensory, visual, and autonomic systems as well as brain circuits implicated in cognition and emotion.

Due to the complexity and the heterogeneity of the disease course and the clinical symptoms, the search for the appropriate personalized treatment and the disease management remains a challenging issue. Nowadays, it is increasingly recognized that MS treatment and care demand a multi-disciplinary approach, including non-pharmacological interventions, aimed to improve quality of life (QoL) and engagement in daily-life activities. Active-rehabilitation or exercise is currently considered as the form of non-medical interventions that best meets these requirements.

In the context of MS, there is now general agreement on the positive effects of exercise for both relapsing remitting (RR) and progressive (P) MS patients. Significant effects have been described for cardiovascular functions, aerobic capacity, muscular strength and ambulatory performance. Even if clear conclusions cannot be drawn, other outcomes, like balance and depression seem to be positively influenced by exercise. Symptoms linked to autonomic dysfunction caused by sympathovagal imbalance, like altered heart rate variability (HRV) and correlating with the load of inflammation in MS may benefit from exercise, being the physical activity an important modulator of the peripheral nervous system. However, the DMT potential of exercise is still overlooked, since only few studies have investigated the influence of exercise on inflammation and neurodegeneration, the main pathogenic events in MS with unclear and, to some extent, contrasting data.

This longitudinal study aims is designed to enrol at least 35 MS patients to perform a conventional 4 weeks rehabilitation program. Physical therapy will be performed for 6 days/week for 4 weeks and will consist of 3 hours of treatment. The rehabilitation program will be planned by a physician specialized 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. According to the patient's disability status, different therapeutic exercises will be performed by qualified physiotherapists. Moreover, intensity of exercise will be tailored to the level of patient's disability. To avoid fatigue and to increase patient's tolerance to the exercises, compensative pauses will be included. Moreover, genotype analysis from peripheral blood cells will be performed to identify single nucleotide polymorphisms (SNPs) in coding regions and/or gene regulators (microRNA or proteins) involved in MS synaptic transmission alterations, like NGF, PDGF, which might correlate to clinical parameters described as both primary and secondary outcomes.

Statistical analysis will be performed by IBM SPSS Statistics 15.0. Data will be tested for normality distribution through the Kolmogorov-Smirnov test. Differences between pre- and post-values will be analyzed using parametric Student's t-test for matched pairs, or if necessary, nonparametric Wilcoxon signed-rank test for matched pairs. Changes in categorical variables will be assessed by McNemar test. Correlation analysis will be performed by calculating Pearson or Spearman coefficients as appropriate. Data will be presented as the mean (standard deviation, sd) or median (25th- 75th percentile). The significance level is established at p<0.05.

Sample size calculation was performed according to the following criteria. Supposing that in MS patients the cytokine values in particular the TNF levels after exercise therapy decrease in a manner similar to that showed in the study by Hedegaard et al (2008), the investigators can estimate that the therapy will have a medium effect on TNF values, d=0.59, calculating a pre-mean value equal to 2611.2 (standard deviation, sd=1586.96) and post-exercise equal to 1249.1 (sd=1261.89), a correlation between pre-post values equals to -0.326. To detect as significant a moderate effect with a power of 95%, assuming a two-sided a=0.05 and applying a Wilcoxon signed-rank test for matched pairs, the investigators estimate a total number of 35 patients. The analysis was performed by G*POWER v3.1.9.2. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT03735524
Study type Interventional
Source Neuromed IRCCS
Contact Diego Centonze, MD
Phone +39 3934444159
Email centonze@uniroma2.it
Status Not yet recruiting
Phase N/A
Start date May 2019
Completion date May 2021

See also
  Status Clinical Trial Phase
Completed NCT05528666 - Risk Perception in Multiple Sclerosis
Completed NCT03608527 - Adaptive Plasticity Following Rehabilitation in Multiple Sclerosis N/A
Recruiting NCT05532943 - Evaluate the Safety and Efficacy of Allogeneic Umbilical Cord Mesenchymal Stem Cells in Patients With Multiple Sclerosis Phase 1/Phase 2
Completed NCT02486640 - Evaluation of Potential Predictors of Adherence by Investigating a Representative Cohort of Multiple Sclerosis (MS) Patients in Germany Treated With Betaferon
Completed NCT01324232 - Safety and Efficacy of AVP-923 in the Treatment of Central Neuropathic Pain in Multiple Sclerosis Phase 2
Completed NCT04546698 - 5-HT7 Receptor Implication in Inflammatory Mechanisms in Multiple Sclerosis
Active, not recruiting NCT04380220 - Coagulation/Complement Activation and Cerebral Hypoperfusion in Relapsing-remitting Multiple Sclerosis
Completed NCT02835677 - Integrating Caregiver Support Into MS Care N/A
Completed NCT03686826 - Feasibility and Reliability of Multimodal Evoked Potentials
Recruiting NCT05964829 - Impact of the Cionic Neural Sleeve on Mobility in Multiple Sclerosis N/A
Withdrawn NCT06021561 - Orofacial Pain in Multiple Sclerosis
Completed NCT03653585 - Cortical Lesions in Patients With Multiple Sclerosis
Recruiting NCT04798651 - Pathogenicity of B and CD4 T Cell Subsets in Multiple Sclerosis N/A
Active, not recruiting NCT05054140 - Study to Evaluate Efficacy, Safety, and Tolerability of IMU-838 in Patients With Progressive Multiple Sclerosis Phase 2
Completed NCT05447143 - Effect of Home Exercise Program on Various Parameters in Patients With Multiple Sclerosis N/A
Recruiting NCT06195644 - Effect of Galvanic Vestibular Stimulation on Cortical Excitability and Hand Dexterity in Multiple Sclerosis Patients Phase 1
Completed NCT04147052 - iSLEEPms: An Internet-Delivered Intervention for Sleep Disturbance in Multiple Sclerosis N/A
Completed NCT03591809 - Combined Exercise Training in Patients With Multiple Sclerosis N/A
Completed NCT03594357 - Cognitive Functions in Patients With Multiple Sclerosis
Completed NCT03269175 - BENEFIT 15 Long-term Follow-up Study of the BENEFIT and BENEFIT Follow-up Studies Phase 4