Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Aerobic Training Effects on Motor and Cognitive Performances in MS: an Exploratory Study With Structural and Functional MRI

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04097418
Recruitment Status : Recruiting
First Posted : September 20, 2019
Last Update Posted : September 20, 2019
Sponsor:
Information provided by (Responsible Party):
Prof. Massimo Filippi, IRCCS San Raffaele

Brief Summary:

Aerobic training (AT) induces cardiovascular, metabolic and muscular changes and has been proposed as a promising rehabilitative approach in elderly adults and in neurological patients to improve both motor and cognitive performances. The Investigators wish to explore the role of AT in multiple sclerosis (MS) patients on physical and neuropsychological functions and its underlying anatomical and functional substrates, using advanced magnetic resonance imaging (MRI) methods.

In this project, the Investigators wish to apply aerobic training in right-handed MS patients and healthy controls to assess:

  1. the effects of aerobic training compared to conventional motor training on motor and cardio-vascular parameters;
  2. the effect of aerobic training compared to conventional motor training on cognitive performance, depression and fatigue;
  3. the modifications of functional activations during a cognitive task and of functional connectivity in motor and cognitive networks during resting state following aerobic training and conventional motor training (functional plasticity);
  4. the regional variations of gray matter (GM) volumes and white matter (WM) architecture after aerobic training and conventional motor training (structural plasticity);
  5. the correlations between the changes detected with structural and functional MRI and clinical, motor and neuropsychological scales.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Behavioral: Aerobic training compared to conventional motor training Not Applicable

  Show Detailed Description

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 80 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

This study is a monocentric, non-pharmacological, longitudinal, randomized, blind, controlled study.

Subjects The Investigators will study 40 MS patients and 40 HC. Subjects will then be randomized through a sequence generated by the computer to determine their assignment to the conventional motor rehabilitation therapy group (control group) or to the aerobic training (experimental group). The computerized randomization software will generate personal codes to allocate every patient to a treatment arm.

Participants will be split into 4 groups of 20 subjects per group:

  1. Group of aerobic training of healthy subjects: aerobic training by treadmill at moderate intensity;
  2. Group of conventional motor training of healthy subjects: training of passive mobility, stretching and balance;
  3. Group of aerobic training of MS patients: aerobic training by treadmill at moderate intensity;
  4. Treatment group control of MS patients: training of passive mobility, stretching and balance.
Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
Masking Description: The computerized randomization software will generate personal codes to allocate every patient to a treatment arm. These codes will be placed in opaque envelopes and delivered to the patient by an operator external to the study.
Primary Purpose: Treatment
Official Title: Effects of Aerobic Training on Motor and Cognitive Performances in Patients With MS: an Exploratory Study With Structural and Functional MRI
Actual Study Start Date : June 13, 2015
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Aerobic training in healthy subjects

For each healthy subject, the treatment will lasts 8 weeks. Each treatment will consists of 35 minutes of training, administered 3 times per week.

Subjects of the experimental groups (both patients and healthy controls) will carry out an aerobic training of moderate intensity (fixed time and variable intensity) on a treadmill. The training will be set individually via direct method: during the first session, the subject will be trained at an intensity that gets the heart rate (HR) corresponding to 46-63% of VO2 peak measured during the exercise test; in subsequent sessions the intensity will increase to maintain the same HR, which will be always monitored. The intensity workout identified will be maintained for 30 minutes each session, preceded and followed by a few minutes of warm-up and cool-down.

Behavioral: Aerobic training compared to conventional motor training

Aerobic training: aerobic training by treadmill at moderate intensity. Each treatment will consists of 35 minutes of training, administered 3 times per week, for 8 weeks.

Conventional motor training: 15 minutes of passive mobilization of upper and lower limbs and spine, 5 minutes of stretching of the upper and the lower limbs and 10 minutes of balance training, administered 3 times per week, for 8 weeks.

Other Name: Conventional motor training

Active Comparator: Conventional motor training of healthy subjects

For each healthy subject, the treatment will lasts 8 weeks. Each treatment will consists of 35 minutes of training, administered 3 times per week.

Control groups of both patients and healthy subjects will follow a conventional non-aerobic physiotherapy training, structured in: 15 minutes of passive mobilization of upper and lower limbs and spine, 5 minutes of stretching of the upper and the lower limbs and 10 minutes of balance training.

Behavioral: Aerobic training compared to conventional motor training

Aerobic training: aerobic training by treadmill at moderate intensity. Each treatment will consists of 35 minutes of training, administered 3 times per week, for 8 weeks.

Conventional motor training: 15 minutes of passive mobilization of upper and lower limbs and spine, 5 minutes of stretching of the upper and the lower limbs and 10 minutes of balance training, administered 3 times per week, for 8 weeks.

Other Name: Conventional motor training

Experimental: Aerobic training in MS patients

For each MS patient, the treatment will lasts 8 weeks. Each treatment will consists of 35 minutes of training, administered 3 times per week.

Subjects of the experimental groups (both patients and healthy controls) will carry out an aerobic training of moderate intensity (fixed time and variable intensity) on a treadmill. The training will be set individually via direct method: during the first session, the subject will be trained at an intensity that gets the heart rate (HR) corresponding to 46-63% of VO2 peak measured during the exercise test; in subsequent sessions the intensity will increase to maintain the same HR, which will be always monitored. The intensity workout identified will be maintained for 30 minutes each session, preceded and followed by a few minutes of warm-up and cool-down.

Behavioral: Aerobic training compared to conventional motor training

Aerobic training: aerobic training by treadmill at moderate intensity. Each treatment will consists of 35 minutes of training, administered 3 times per week, for 8 weeks.

Conventional motor training: 15 minutes of passive mobilization of upper and lower limbs and spine, 5 minutes of stretching of the upper and the lower limbs and 10 minutes of balance training, administered 3 times per week, for 8 weeks.

Other Name: Conventional motor training

Active Comparator: Conventional motor training of MS patients

For each MS patient, the treatment will lasts 8 weeks. Each treatment will consists of 35 minutes of training, administered 3 times per week.

Control groups of both patients and healthy subjects will follow a conventional non-aerobic physiotherapy training, structured in: 15 minutes of passive mobilization of upper and lower limbs and spine, 5 minutes of stretching of the upper and the lower limbs and 10 minutes of balance training.

Behavioral: Aerobic training compared to conventional motor training

Aerobic training: aerobic training by treadmill at moderate intensity. Each treatment will consists of 35 minutes of training, administered 3 times per week, for 8 weeks.

Conventional motor training: 15 minutes of passive mobilization of upper and lower limbs and spine, 5 minutes of stretching of the upper and the lower limbs and 10 minutes of balance training, administered 3 times per week, for 8 weeks.

Other Name: Conventional motor training




Primary Outcome Measures :
  1. Longitudinal changes of brain GM volumes following aerobic training or conventional motor training [ Time Frame: 2 months ]
    Tensor-Based Morphometry will be applied on 3D T1-weighted sequence to evaluate regional GM volume changes that will be reported as t values, ranging from 0 (no statistically significant changes) to infinity (highly statistically significant changes).

  2. Longitudinal changes of WM microstructural abnormalities following aerobic training or conventional motor training [ Time Frame: 2 months ]
    Tract-based Spatial Statistics will be applied on diffusion-tensor MRI sequence to evaluate longitudinal changes of fractional anisotropy (a dimensionless quantity ranging from 0 [more severe damage] to 1 [less severe damage]), mean diffusivity (expressed in [(mm^2)/s]×10^-3 and ranging from 0 [less severe damage] to infinity [more severe damage]), axial diffusivity (expressed in [(mm^2)/s]×10^-3 and ranging from 0 [less severe damage] to infinity [more severe damage]) and radial diffusivity (expressed in [(mm^2)/s]×10^-3 and ranging from 0 [less severe damage] to infinity [more severe damage]). Longitudinal WM microstructural changes will be reported as t values, ranging from 0 (no statistically significant changes) to infinity (highly statistically significant changes).

  3. Resting State Functional Connectivity MRI changes following aerobic training or conventional motor training [ Time Frame: 2 months ]

    Group independent component analysis Of fMRI Toolbox (GIFT) software will be applied to evaluate the modifications of resting state functional connectivity. This will be reported as z-scores, ranging from minus infinity (reduced connectivity) to infinity (increased connectivity).

    Longitudinal changes in resting state functional connectivity will be obtained subtracting baseline z-score to z-score at follow-up. A positive score means increased connectivity, a negative score, a decreased connectivity.


  4. Functional MRI changes following aerobic training or conventional motor training [ Time Frame: 2 months ]
    Statistical Parametric Mapping 12 will be applied to functional MRI sequence acquired during the Stroop task to evaluate the modifications of functional activations during this cognitive task. They will be reported as t values, ranging from 0 (no statistically significant changes) to infinity (highly statistically significant changes).

  5. Effects of aerobic training compared to conventional motor training on global clinical disability [ Time Frame: 2 months ]
    Rating of Expanded Disability Status Scale (EDSS) score changes: EDSS is a scale ranging from 0 (no disability) to 10 (death due to multiple sclerosis). Longitudinal changes will be obtained subtracting baseline EDSS to EDSS at follow-up. A positive score means disability worsening, a negative score, an improvement in disability.

  6. Effects of aerobic training compared to conventional motor training on clinical disability [ Time Frame: 2 months ]
    Rating of Multiple Sclerosis Functional Composite (MSFC) score changes: the MSFC a composite score ranging from minus infinity (worse performances) to infinity (better performances) obtained from the sum of the z-scores derived from 1) Paced Auditory Serial Addition Test (PASAT) to evaluate cognitive functions, 2) timed 25-foot walk test to evaluate walking speed, and 3) nine-hole peg test to evaluate arm and hand dexterity. Longitudinal changes will be obtained subtracting baseline MSFC to MSFC at follow-up. A positive score means disability improvement, a negative score, a worsening in disability.

  7. Effects of aerobic training compared to conventional motor training on behavioural measures [ Time Frame: 2 months ]
    Rating of functional Independent measurement (FIM) scale changes: the FIM scale is an 18-item of physical, psychological and social functions, ranging from 18 (worse disability) to 126 (total autonomy) and obtained from the sum of 18 items, each of them ranging from 1 to 7. Longitudinal changes will be obtained subtracting baseline FIM to FIM at follow-up. A positive score means behavioural improvements, a negative score, a worsening in behavioural functions.

  8. Effects of aerobic training compared to conventional motor training on spasticity [ Time Frame: 2 months ]

    Rating of Modified Ashworth Scale changes: the Modified Ashworth Scale is a 6-point scale, ranging from 0 to 4, where lower scores represent normal muscle tone and higher scores represent spasticity or increased resistance to passive movement.

    Longitudinal changes will be obtained subtracting baseline Modified Ashworth scale to Modified Ashworth scale at follow-up. A positive score means spasticity worsening, a negative score, an improvement in spasticity.


  9. Effects of aerobic training compared to conventional motor training on walking ability [ Time Frame: 2 months ]

    Assessment of Six minutes walking test changes: this is a submaximal exercise test that entails measurement of distance walked over a span of 6 minutes. It is expressed in meters and ranges from 0 (worse performance) to infinity (better performance).

    Longitudinal changes will be obtained subtracting baseline distance to distance walked at follow-up. A positive score means walking improvement, a negative score, a worsening of walking ability.


  10. Effects of aerobic training compared to conventional motor training on person's mobility [ Time Frame: 2 months ]

    Assessment of Time up-and-go test changes: this is test assessing both static and dynamic balance. It uses the time (expressed in seconds) that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down. It ranges from 0 (better performance) to infinity (worse performance).

    Longitudinal changes will be obtained subtracting baseline seconds to seconds needed at follow-up. A positive score means performance worsening, a negative score, an improvement in the performance.



Secondary Outcome Measures :
  1. Effects of aerobic training compared to conventional motor training on cognitive functions [ Time Frame: 2 months ]
    Longitudinal changes of the performances at the Brief Repeatable Battery of Neuropsychological Tests and Digit Span (forward and backward): Longitudinal changes will be obtained subtracting baseline z-scores to z-scores at follow-up. A positive score means cognitive improvement, a negative score, a worsening of cognitive performance.

  2. Effects of aerobic training compared to conventional motor training on fatigue [ Time Frame: 2 months ]
    Assessment of Modified Fatigue Impact Scale (MFIS) changes: The MFIS score is a composite score that can range from 0 (no fatigue) to 84 (highest fatigue) and that is computed by adding sub-scores from physical, cognitive, and psychosocial subscales. Longitudinal changes will be obtained subtracting baseline MFIS to MFIS at follow-up. A positive score means fatigue worsening, a negative score, an improvement in fatigue.

  3. Effects of aerobic training compared to conventional motor training on depression [ Time Frame: 2 months ]
    Assessment of Beck Depression Inventory II (BDI-II) changes: the BDI-II is a 21-question multiple-choice self-report inventory ranging from 0 (no depression to 63 severe depression). The MFIS score is a composite score that can range from 0 (no fatigue) to 84 (highest fatigue) and that is computed by adding sub-scores from physical, cognitive, and psychosocial subscales. Longitudinal changes will be obtained subtracting baseline BDI-II score to BDI-II score at follow-up. A positive score means depression, a negative score, an improvement in depression.

  4. Effects of aerobic training compared to conventional motor training on quality of life [ Time Frame: 2 months ]
    Assessment of Multiple Sclerosis Quality of Life Scale (MSQOL-54) changes: the MSQOL-54 is a 54-item scale generated from 12 subscales and two additional single-item measures and ranging from 0 (worse quality of life) to 100 (better quality of life). Longitudinal changes will be obtained subtracting baseline MSQOL-54 to MSQOL-54 at follow-up. A positive score means quality of life improvement, a negative score, a worsening of quality of life.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion criteria (All)

  • Age between 18 and 65 years;
  • Native italian language speaking;
  • Right-handed;
  • No particular motor skills;
  • No additional neurologic, psychiatric, orthopaedic or rheumatologic diseases;
  • Normal or corrected-to-normal vision;
  • No contraindications to MRI;
  • Ability to understand the purpose of the study and provide signed informed consent.

For MS patients, the following additional inclusion criteria will be applied:

  • Patients with a diagnosis of MS, regardless of sex, duration and course of the disease;
  • EDSS score ranging from 0 to 6.0 (included);
  • Stable treatment for MS from at least 1 month prior to study enrolment;
  • Relapse- and steroid-free from at least 3 months before screening visit;
  • An indication to perform a physiotherapy treatment by the treating physician.

Exclusion Criteria:

  • Persons who perform regularly a structured training;
  • Patients who performed a physiotherapy treatment for at least 3 months;
  • Concomitant therapy with antidepressant, baclofen, psychoactive, and steroids drugs as well as symptomatic treatment for fatigue;
  • History of alcohol or substance abuse;
  • Pregnancy or breastfeeding.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04097418


Contacts
Layout table for location contacts
Contact: Massimo Filippi, MD 00390226433054 filippi.massimo@hsr.it
Contact: Maria Assunta Rocca, MD 00390226433019 rocca.mara@hsr.it

Locations
Layout table for location information
Italy
IRCCS San Raffaele Recruiting
Milan, Italy, 20132
Contact: Massimo Filippi, MD    00390226433054    filippi.massimo@hsr.it   
Contact: Maria Assunta Rocca, MD    00390226433019    rocca.mara@hsr.it   
Sponsors and Collaborators
IRCCS San Raffaele
Investigators
Layout table for investigator information
Principal Investigator: Massimo Filippi, MD IRCCS San Raffaele

Publications:

Layout table for additonal information
Responsible Party: Prof. Massimo Filippi, Head of Neurology, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT04097418     History of Changes
Other Study ID Numbers: Training aerobico-SM 2015
First Posted: September 20, 2019    Key Record Dates
Last Update Posted: September 20, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The dataset including all the data obtained from this study will be available from the Principal Investigator upon reasonable request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: The dataset including all the data obtained from this study will be available 6 months after the publication of the results.
Access Criteria: The dataset including all the data obtained from this study will be available from the Principal Investigator upon reasonable request.

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Prof. Massimo Filippi, IRCCS San Raffaele:
Multiple Sclerosis
Aerobic Training
rehabilitation
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases