Exercise in Multiple Sclerosis: Effects on Cognitive Function and Brain Connectivity (AERCONN)
|ClinicalTrials.gov Identifier: NCT02005237|
Recruitment Status : Completed
First Posted : December 9, 2013
Last Update Posted : June 26, 2017
Cognitive dysfunction is frequent in patients with multiple sclerosis (MS) and to date, there are no available treatments to improve cognition in this patient population. Some evidence from animal studies and small clinical trials suggest that aerobic exercise might beneficially affect cognitive function in MS. The aim of this randomized-controlled trial is to explore if an aerobic exercise training program can enhance cognition in MS. In addition, we will employ neuroimaging markers to determine if exercise alters measures of brain structure and function.
Patients will be randomly assigned to either a 3-months exercise program (bicycle ergometry, 2-3 session per week) or a waitlist control group. The primary endpoint of the study is a test of verbal learning and memory. Secondary endpoints include neuroimaging markers of functional and structural connectivity in the brain. We hypothesize that exercise will improve verbal learning and memory and beneficially affect measures of brain connectivity.
|Condition or disease||Intervention/treatment||Phase|
|Multiple Sclerosis||Behavioral: Aerobic Exercise||Not Applicable|
Background: Cognitive dysfunction is frequent in patients with multiple sclerosis (MS) and to date, there are no available treatments to improve cognition in this patient population. Some evidence from animal studies and small clinical trials suggest that aerobic exercise might beneficially affect cognitive function in MS.
Aims: This study aims to explore the potential of an aerobic exercise program on brain structure and function in MS in a single-blind, randomized controlled phase IIa trial. We hypothesize that exercise will improve verbal learning and memory (primary endpoint) as well as induce changes in neuroimaging markers of structural and functional central nervous system (CNS) connectivity (secondary endpoints). Tertiary outcomes will include walking ability, motor function and coordination, as well as patient-based outcomes (depression, fatigue, and health-related quality of life).
Design: This is a single-blind, randomized, controlled phase IIa trial with a parallel group design comparing 3 months of standardized aerobic exercise training (bicycle ergometry) to a waitlist control group (superiority framework). The allocation ratio of exercise to waitlist control is 1:1 with a sample size of n=60.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||68 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Double (Investigator, Outcomes Assessor)|
|Official Title:||Randomized Controlled Trial Investigating the Effects of a Standardized Aerobic Exercise Intervention on Cognitive Function and Brain Connectivity in Relapsing-remitting Multiple Sclerosis|
|Study Start Date :||December 2013|
|Actual Primary Completion Date :||May 2016|
|Actual Study Completion Date :||November 2016|
Experimental: Aerobic Exercise (12 Weeks)
Aerobic exercise on a bicycle ergometer, tailored to the individual's level of fitness. Duration: 12 weeks with 2-3 sessions per week.
Behavioral: Aerobic Exercise
3-months exercise program tailored to the individual level of aerobic fitness. Patients will exercise on a bicycle ergometer (2-3 session per week) according to a predefined training plan with increasing duration and intensity
No Intervention: Waitlist Control Group
No intervention (patients randomized to this group will be offered access to the training program after completion of the trial)
- Change in Verbal Learning and Memory [ Time Frame: Baseline and at Month 3 (end of intervention) ]Verbal Learning and Memory will be assessed with the Verbal Learning and Memory Test (VLMT)
- Change in Functional Connectivity [ Time Frame: Baseline and at Month 3 (end of intervention) ]Functional connectivity of CNS networks will be assessed by resting-state functional magnetic resonance imaging (rs fMRI) and resting-state magnetoencephalography (rs MEG)
- Change in Structural Connectivity [ Time Frame: Baseline and at Month 3 (end of intervention) ]Structural connectivity and integrity of CNS networks will be assessed by diffusion tensor imaging (DTI) as well as measures of gray matter density using magnetic resonance imaging (MRI)
- Change in Neuropsychological Function [ Time Frame: Baseline and at Month 3 (end of intervention) ]Neuropsychological function will be assessed using a standardized battery covering the following domains: visuospatial learning and memory, attention, processing speed, working memory, and social cognition
- Change in Patient-Reported Outcomes [ Time Frame: Baseline and at Month 3 (end of intervention) ]Patient-reported outcomes will be assessed for depressive symptoms (IDS-30SR), fatigue (FSMC), quality of life (HAQUAMS), and walking (MSWS-12)
- Change in Walking Ability [ Time Frame: Baseline and at Month 3 (end of intervention) ]Walking ability will be assessed using the six-minute-walk test (6MWT) as well as Actibelt accelerometry
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02005237
|University Hospital Hamburg-Eppendorf|
|Hamburg, Germany, 20241|
|Principal Investigator:||Stefan M Gold, PhD||Center for Molecular Neurobiology, University Hospital Hamburg Eppendorf|
|Principal Investigator:||Andreas K Engel, MD||Dept Neurophysiology, University Hospital Hamburg Eppendorf|
|Principal Investigator:||Christoph Heesen, MD||Dept Neurology, University Hospital Hamburg Eppendorf|
|Principal Investigator:||Guido Nolte, PhD||Dept Neurophysiology, University Hospital Hamburg Eppendorf|
|Principal Investigator:||Karl-Heinz Schulz, MD, PhD||Dept Sports Medicine, University Hospital Hamburg Eppendorf|