Intensity-dependent Impacts of Training on Growth Factors BDNF and Cognitive Functions in Persons With Multiple Sclerosis - a Single-center Randomized Controlled Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Neurotrophic Factor BDNF
研究概览
简要总结
Multiple Sclerosis (MS) is a chronic immune-mediated disease of the central nervous system, accompanied by varying inflammatory manifestations, demyelinization and axonal loss. With chronic progressive or relapsing-remitting disease onsets persons with MS (pwMS) progressively develop impaired functional capacity and show reduced physical activity and cognitive decline compared to healthy controls. The primary aims of rehabilitation in pwMS are therefore to increase levels of activity and participation leading to increase independence of the participants. In general exercise ranges from passive physiotherapy-based interventions to submaximal endurance training sessions. Current recommendations advise pwMS that exercise should be matched with the individual performance capacities. Exercise training in pwMS then has the potential to target and improve many components outlined in the ICF-model.
Cytokines and neurotrophic factors have received increased attention in MS research and addressed the brain-derived neurotrophic factor (BDNF) as an important mediator of neuronal regeneration linking the effects of exercise with MS pathogenesis. Data show positive connections between elevated neurotrophin concentrations, induction of neuroplasticity, recovery of the motor and cognitive functions and the applied training intensities. Similarly, intensive and progressive exercise bouts seem to have greater benefits on cardiorespiratory fitness and maximum voluntary strength in elderly and seniors with dementia. Therefore, specific exercise prescriptions may be necessary for targeting the specific impairments also in pwMS.
This study aims to evaluate two different training modalities (intensive versus normal) in pwMS. It is expected that both modalities will improve cardiorespiratory fitness and cognitive functions in pwMS. Based on the findings that higher training intensities facilitate greater benefits, it is expected that pwMS will tolerate the intensive training intensities and show positive connections to elevated neurotrophin concentrations.
The results will to help to clearer understand the benefits of each type of exercise conveyed for pwMS and will assist in the development of patient-specific exercise prescriptions.
详细描述
This study aims to evaluate two different training modalities (intensive versus normal) in pwMS. It is expected that both modalities will improve cardiorespiratory fitness and cognitive functions in pwMS. Based on the findings that higher training intensities facilitate greater benefits, it is expected that pwMS will tolerate the intensive training intensities and show positive connections to elevated neurotrophin concentrations.
Primary outcomes are the acute (after CPET) and chronic (3-week training intervention) changes of neurotrophic factors and cognitive functions. All other measures are secondary outcomes (Training values: VO2peak, Workload, Heart rate; Fatigue: FSMC; Anxiety and Depression: HADS.
Participants are eligible if they hold a definite diagnosis of multiple sclerosis (revised McDonald criteria), an EDSS score of 1.0 -6.0, they give no written consent, severe cardiovascular exacerbations (RR > 240/120, HR above the age predicted maximum of 220-Age) are persistent, they hold severe cognitive impairments, they face severe disease progression or relapses.
Main measurements and procedures include:
Blood sampling: Blood samples (10ml) of the primary outcomes will be taken by vein puncture from the antecubital vein in a seated position before the exercise bout and straight after reaching VO2peak during cool down, with the participant still seated on the ergometer.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •for the participants' eligibility are a definite MS diagnosis (McDonald criteria). Participants fulfilling the key inclusion and the following criteria are eligible for this study
- •EDSS 1.0 - 6.0
- •Age 19 - 75 years
- •The presence of any one of the following
排除标准
- •will lead to exclusion of the participant:
- •Persistent infections
- •Severe cardiovascular and pulmonal diseases (renal failure, hepatic dysfunction, cardiovascular disease)
- •Severe cardiovascular exacerbations (RR > 240/120, HR above the age predicted maximum of 220-Age) during training
- •Immunosuppressive therapy the day of CPET
- •Life style factors and / or persistent addictions (drug or alcohol abuse)
- •Inability to follow the study procedures (due to psychological disorders or dementia)
- •Insufficient knowledge of the project language (German)
- •Women who are pregnant or breast feeding,
- •Intention to become pregnant during the course of the study,
- •Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration, such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases.
- •Participation in another study with investigational drug within the 30 days preceding and during the present study,
- •Previous enrolment into the current study,
- •Enrolment of the investigator, his / her family members, employees and other dependent persons,
- •Specific exclusions for the disease under study,
- •Specific concomitant therapy washout requirements prior to and/or during study participation,
- •Dietary restrictions
- •Exclusion Criteria: Criteria in which the participant withdraws from this study may be the following:
- •Inability to comply with the daily schedule
- •Strong symptom exacerbations
- •Withdrawal of informed consent
- •Non-compliance
- •Disease progression or relapse
研究组 & 干预措施
Intensive Training
Treatment consists of endurance training in both groups of physiologically defined heart rate controlled cycling at 50-60 rounds per minutes (rpm) and progressive resistance training. Training groups differ in the applied intensities and frequencies.The IT will train less frequent but training sessions will be more intensive in its effects. Training will be performed daily in six sessions (three morning and three afternoon sessions), synchronized and individually matched to a ratio of active versus passive sessions of 2:1.
干预措施: Intensive Training (Behavioral)
Normal Training
The NT is the normal training performed out of the daily routine and outlines the usual care of the Valens clinic. Training will be performed in up to eight training sessions that will not be synchronized and not individually matched to a ratio of active versus passive sessions.
干预措施: Normal Training (Behavioral)
结局指标
主要结局
Neurotrophic Factor BDNF
时间窗: 3-weeks
Short- and long-term changes (pg/ml) of serum levels of the neurotrophic factor BDNF (t1--\>t2)
次要结局
- Maximum Oxygen consumption (VO2peak)(3-weeks)
- Maximum heart rate (HRmax)(3-weeks)
- Maximum workload (Loadmax)(3-weeks)
- Fatigue(3-weeks)
- Health-related Quality of life(3-weeks)
- Cognitive Functions(3-weeks)
研究者
Jens Bansi
Exercise Sciences, PhD
Klinik Valens