Effects of Aerobic Training on Motor and Cognitive Performances in Patients With MS: an Exploratory Study With Structural and Functional MRI
试验速览
- 阶段
- 不适用
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- Resting State Functional Connectivity MRI changes following aerobic training or conventional motor training
研究概览
简要总结
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:
- the effects of aerobic training compared to conventional motor training on motor and cardio-vascular parameters;
- the effect of aerobic training compared to conventional motor training on cognitive performance, depression and fatigue;
- 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);
- the regional variations of gray matter (GM) volumes and white matter (WM) architecture after aerobic training and conventional motor training (structural plasticity);
- the correlations between the changes detected with structural and functional MRI and clinical, motor and neuropsychological scales.
详细描述
This study is a monocentric, non-pharmacological, longitudinal, randomized, blind, controlled study.
Subjects The Investigators will study 40 right-handed MS patients with Expanded Disability Status Scale (EDSS) score ≤6 and an indication to perform a physiotherapy treatment by the treating physician. Patients will be recruited from the Department of Neurology, San Raffaele Hospital. Forty sex- and age-matched right-handed healthy individuals (HC) will also be enrolled. The HC will be recruited from the patients' relatives or acquaintances of the study personnel. The enrolment of HC is crucial to define whether post-treatment changes observed in MS patients are adaptive or maladaptive and to estimate the magnitude of these alterations.
Subjects who will satisfy the inclusion criteria 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. These codes will be placed in opaque envelopes and delivered to the patient by an operator external to the study.
Thus, participants will be split into 4 groups of 20 subjects per group:
- Experimental group of HC: aerobic training by treadmill at moderate intensity;
- Control group of HC: training of passive mobility, stretching and balance;
- Experimental group of MS patients: aerobic training by treadmill at moderate intensity;
- Control group of MS patients: training of passive mobility, stretching and balance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
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.
干预措施: Aerobic training compared to conventional motor training (Behavioral)
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.
干预措施: Aerobic training compared to conventional motor training (Behavioral)
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.
干预措施: Aerobic training compared to conventional motor training (Behavioral)
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.
干预措施: Aerobic training compared to conventional motor training (Behavioral)
结局指标
主要结局
Resting State Functional Connectivity MRI changes following aerobic training or conventional motor training
时间窗: 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.
Functional MRI changes following aerobic training or conventional motor training
时间窗: 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).
Effects of aerobic training compared to conventional motor training on global clinical disability
时间窗: 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.
Effects of aerobic training compared to conventional motor training on walking ability
时间窗: 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.
Longitudinal changes of brain GM volumes following aerobic training or conventional motor training
时间窗: 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).
Effects of aerobic training compared to conventional motor training on clinical disability
时间窗: 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.
Effects of aerobic training compared to conventional motor training on person's mobility
时间窗: 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.
Longitudinal changes of WM microstructural abnormalities following aerobic training or conventional motor training
时间窗: 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).
Effects of aerobic training compared to conventional motor training on behavioural measures
时间窗: 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.
Effects of aerobic training compared to conventional motor training on spasticity
时间窗: 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.
次要结局
- Effects of aerobic training compared to conventional motor training on depression(2 months)
- Effects of aerobic training compared to conventional motor training on cognitive functions(2 months)
- Effects of aerobic training compared to conventional motor training on fatigue(2 months)
- Effects of aerobic training compared to conventional motor training on quality of life(2 months)
研究者
Prof. Massimo Filippi
Head of Neurology
IRCCS San Raffaele