A randomized controlled phase IIa trial investigating the effects of a standardized aerobic exercise intervention on cognitive function and brain connectivity in relapsing-remitting multiple sclerosis. (AERCONN)

Trial Acronym: AERCONN

Interdisziplinäres Projekt zusammen mit dem Zentrum für Molekulare Neurobiologie, der Klinik fürNeurologie, der Neuroradiologie und dem Institut für Neurophysiologie, UKE

German study title: Einfluss von aerobem Sporttraining auf kognitive Funktionen und Konnektivität bei multipler Sklerose.

Gefördert durch das BMBF


Multiple sclerosis (MS) is one of the most common neurological disorders of the central nervous system among young adults. Symptoms comprise loss of sensory, motor, vegetative, visual and cognitive functions. The progressive loss of cognitive skills ranges among the most severe symptoms of the disease and has a strong impact on patients quality of life.  Studies in MS indicate that exercise has a positive effect on cognition. Studies in healthy or ageing individuals indicate that physical activity can influence brain-connectivity and neuroplasticity in the central nervous system by applying functional Magnetic Resonance Imaging or Magnetoencephalography. The present study investigates effects of a standardized aerobic intervention on cognitive function and brain connectivity in relapsing-remitting MS-patients.


The trial is a single-blinded, randomized, controlled single-centre phase IIa study. Patients diagnosed with relapsing, remitting MS aged between 18 and 65 years, with a disease duration ≤10 years and a disability score ≤ 3.5 are recruited. We expect to enroll 60 patients.

Participants are randomized into an intervention group who starts with physical exercise for 3 months or a wait-list control group, which will receive the intervention after 6 months. Exercise comprises 2-3 weekly aerobic trainings on a bicycle. Every participant will receive an individual training plan based on an exertion test. Outcome parameters will be assessed at baseline (week 0), after the intervention (month 3), and at follow-up (month 6).

Figure 1

Figure 1: Trial Design

These include clinical assessment (neurological scoring and neuropsychological testing), magnetic resonance imaging (structural and functional MRI), magnetencephalography (MEG), and assessments of physical fitness. The primary outcome measure is the immediate and delayed recall and recognition memory assessed with Verbal Learning and Memory test (VLMT). Functional connectivity detected by resting state MEG and functional MRI, structural integrity and connectivity represented by changes in Grey Matter (GM)-density and Diffusion Tensor Imaging (DTI) and other cognitive functions assessed with a neuropsychological battery will serve as secondary endpoints. Furthermore, walking ability, motor coordination, balance and quality of life will be assessed.


If our results will prove a beneficial effect, our trial will have major clinical relevance, towards implementing physical exercise as a standard intervention in relapsing-remitting multiple sclerosis. Furthermore, this study will generate valuable information about the influence of physical activity on brain connectivity and neuroplasticity.