Influence of combined functional resistance and endurance exercise over 12 weeks on matrix metalloproteinase-2 serum concentration in persons with relapsing-remitting multiple sclerosis - a community-based randomized controlled trial.
BMC neurology. 2019;19(1):314
Plain language summary
Multiple Sclerosis (MS) is a degenerative autoimmune neuroinflammatory disease where the blood-brain barrier is compromised, causing inflammation. Regular exercise has been shown to support psychomotor symptoms and improve mobility. This trial examines the effects of resistance and endurance exercise in 64 patients, aged 18-45 years, with relapsing-remitting MS (RRMS). The patients are divided into an exercise group and a passive group. The exercise group will perform 60 min of combined functional resistance and endurance exercises 3x per week over a period of 12 weeks. Blood samples will be taken to measure proteolytic matrix metalloproteinases (MMP) as an indicator of neurological inflammation. Secondary measures will also be taken to evaluate patient-reported outcomes regarding gait, sleep, depression, anxiety, fatigue, and quality of life. The study is currently ongoing, so the results are not yet published. From an ethical perspective the passive group will also be offered the opportunity to perform the same exercises at the end of the trial.
BACKGROUND The relevance of regular moderate to intense exercise for ameliorating psychomotor symptoms in persons with multiple sclerosis (pwMS) is becoming increasingly evident. Over the last two decades, emerging evidence from clinical studies and animal models indicate immune regulatory mechanisms in both periphery and the central nervous system that may underlie these beneficial effects. The integrity of the blood-brain barrier as the main structural interface between periphery and brain seems to play an important role in MS. Reducing the secretion of proteolytic matrix metalloproteinases (MMP), i.e. MMP-2, as disruptors of blood-brain barrier integrity could have profound implications for MS. METHODS In this two-armed randomized controlled trial 64 participants with relapsing-remitting MS (RRMS) (EDSS 0-4.0) will be allocated to either an intervention group or a passive wait list control group. The intervention group will perform 60 min of combined functional resistance and endurance exercises 3x per week over a period of 12 weeks in a community-based and publicly available setting. Changes in serum concentration of MMP-2 will be the primary outcome. Secondary outcomes are numbers of immune cell subsets, soluble (anti-) inflammatory factors, physical capacity, cognitive performance, physical activity behavior, gait performance, and patient-reported outcomes. All outcome measures will be assessed at baseline and after week 12 with an additional blood sampling before, during and immediately after a single training session in week 6. DISCUSSION To our knowledge, this will be the first RCT to investigate both the acute and chronic effects of a community-based intense functional resistance and endurance exercise regimen in persons with RRMS. Combining analysis of biological and cognitive or psychological outcomes may provide a better understanding of the MS-specific symptomology. TRIAL REGISTRATION DRKS00017091; 05th of April, 2019; International Clinical Trials Registry Platform.