Joisten Niklas, Rademacher Annette, Bloch Wilhelm, Schenk Alexander, Oberste Max, Dalgas Ulrik, Langdon Dawn, Caminada Daniel, Purde Mette-Triin, Gonzenbach Roman, Kool Jan, Zimmer Philipp, Bansi Jens
Department of Molecular and Cellular Sport Medicine, Institute of Cardiovascular Research and Sports Medicine, German Sport University Cologne, Am Sportpark Müngersdorf 6, 50933, Cologne, Germany.
Deparment of Neurology, Kliniken-Valens, Rehabilitationsklinik-Valens, Taminaplatz 1, 7317, Valens, Switzerland.
BMC Neurol. 2019 Mar 8;19(1):37. doi: 10.1186/s12883-019-1267-9.
Studies have shown positive effects of therapeutic exercise on motor- and cognitive function as well as on psychosocial outcomes in persons with multiple sclerosis (MS). A reduction of inflammatory stress through physical exercise has been suspected as one key mechanism, mediating the positive effects of exercise in the context of MS. The primary objective of this trial is to investigate the acute and chronic effects of different exercise modalities on (anti-)inflammatory immune signalling as well as on cognitive and functional capacity in persons with MS.
A two armed single-blind randomized controlled design will investigate 72 persons with relapsing remitting or secondary progressive MS (EDSS 3.0-6.0), during 3 weeks of inpatient rehabilitation. Participants will be randomized into either a high-intensity interval training (HIIT) or a moderate continuous training group; the latter represents the local standard therapy (ST). Both groups will exercise 3x per week. The HIIT group will perform 5 × 1.5-min high-intensive exercise bouts at 95-100% of their maximum heart rate (HR) followed by active breaks of unloaded pedalling (60% HR) for 2 min. In contrast, the ST group will exercise for 24 min continuously at 65% of HR. The proportion of circulating regulatory T-cells will be measured as primary outcome. Secondary outcomes comprise numbers and proportions of further immune cells including Th17-cells, soluble factors ((anti-) inflammatory cytokines, tryptophan metabolites), endurance capacity, cognitive performance, processing skills for activities of daily living, fatigue, depression and healthcare-related quality of life. Outcomes will be assessed before (T) and after (T) the 3-week exercise intervention program. Blood samples of T will be taken immediately before the first exercise session. Additionally, blood samples for the soluble factors will be collected immediately after (T) and three hours (T) after the first exercise session of each group.
This study will be the first to investigate both acute and chronic effects of aerobic exercise on immune function and disease associated biomarkers in persons with MS. Combining biological analyses with cognitive and functional capacity assessments may contribute to a better understanding of responses to rehabilitative training, needed to improve exercise recommendations for persons with MS.
This trial was prospectively registered at ClinicalTrials.gov ( NCT03652519 ; 29 August 2018).
研究表明，治疗性运动对多发性硬化症（MS）患者的运动和认知功能以及心理社会结局具有积极影响。体育锻炼减轻炎症应激被怀疑是介导运动在MS背景下产生积极作用的一个关键机制。本试验的主要目的是研究不同运动方式对MS患者（抗）炎症免疫信号以及认知和功能能力的急性和慢性影响。
一项双臂单盲随机对照设计将对72例复发缓解型或继发进展型MS患者（扩展残疾状态量表评分3.0 - 6.0）进行为期3周的住院康复研究。参与者将被随机分为高强度间歇训练（HIIT）组或中等强度持续训练组；后者代表当地标准治疗（ST）。两组均每周锻炼3次。HIIT组将以其最大心率（HR）的95 - 100%进行5次×1.5分钟的高强度运动，随后进行2分钟的无负荷蹬车主动休息（HR的60%）。相比之下，ST组将以HR的65%持续锻炼24分钟。循环调节性T细胞的比例将作为主要结局指标进行测量。次要结局指标包括其他免疫细胞的数量和比例，包括Th17细胞、可溶性因子（（抗）炎症细胞因子、色氨酸代谢产物）、耐力、认知表现、日常生活活动的处理技能、疲劳、抑郁以及与医疗保健相关的生活质量。结局指标将在3周运动干预计划之前（T₀）和之后（T₁）进行评估。T₀的血样将在第一次锻炼 session之前立即采集。此外，可溶性因子的血样将在每组第一次锻炼session之后立即（T₁）和三小时后（T₂）采集。
本研究将首次调查有氧运动对MS患者免疫功能和疾病相关生物标志物的急性和慢性影响。将生物学分析与认知和功能能力评估相结合，可能有助于更好地理解对康复训练的反应，从而改进对MS患者的运动建议。
本试验已在ClinicalTrials.gov上进行前瞻性注册（NCT03652519；2018年8月29日）。
