Study on the Interaction Between Immune, Autonomic and Central Nervous Systems as a Target of Exercise Therapy in Multiple Sclerosis

CompletedNot a drug-phase studyMS (type not specified)NCT04294979

What it found

Paper found, not read

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 progression
  • Changes 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 mobility
  • Changes 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 sleep
  • Changes 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 sleep
  • Neurophysiological assessment

    Changes from baseline (time 0, t0) to the end of the 6-week exercise protocol (time 1, t1)

    Myelin repairNerve conduction tests
  • Changes in autonomic function

    Changes from baseline (time 0, t0) to the end of the 6-week exercise protocol (time 1, t1)

    Walking and mobility
  • Changes 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 response
  • Electrophysiological 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

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History

    1. Started

      Feb 2020

    2. Main results due

      Dec 2023

    3. Finished

      Apr 2024

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