Clinical trial NCT02005237: Exercise in Multiple Sclerosis: Effects on Cognitive Function and Brain Connectivity
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Multiple Sclerosis
Keywords: Exercise
Cognition
Neuroimaging
Rehabilitation
Connectivity
Lead sponsor: Universitätsklinikum Hamburg-Eppendorf
Sponsor class: OTHER
Collaborators: name: German Federal Ministry of Education and Research
First posted: 2013-12-09
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Relapsing-remitting multiple sclerosis according to McDonald criteria
* Currently in remission
* Disease duration \< 10 years
* Low to moderate physical disability (EDSS 0-3.5)
* On stable immunotherapy (\>3 months) or without any planned treatment for the next year

Exclusion Criteria:

* Patients who are not able to understand the study concept due to severe cognitive deficits or psychiatric comorbidity
* Patients currently taking psychoactive drugs
* Patients unable to undergo aerobic exercise training for medical reasons
* Patients with active disease or uncertain stability under current immunomodulatory therapy (as judged by the treating neurologist)
* Patients with implants or body modifications (e.g. dental implants, piercings, tattoos, pacemakers etc.) which might interfere with MEG and MRI assessments
* Patients unable to travel to the study center 2-3 times a week for the duration of the study

Primary outcomes:
measure: Change in Verbal Learning and Memory
timeFrame: Baseline and at Month 3 (end of intervention)
Secondary outcomes:
measure: Change in Functional Connectivity
timeFrame: Baseline and at Month 3 (end of intervention)
measure: Change in Structural Connectivity
timeFrame: Baseline and at Month 3 (end of intervention)
measure: Change in Neuropsychological Function
timeFrame: Baseline and at Month 3 (end of intervention)
Other outcomes:
measure: Change in Patient-Reported Outcomes
timeFrame: Baseline and at Month 3 (end of intervention)
measure: Change in Walking Ability
timeFrame: Baseline and at Month 3 (end of intervention)
Locations:
city: Hamburg
country: Germany
facility: University Hospital Hamburg-Eppendorf
Study officials:
affiliation: Center for Molecular Neurobiology, University Hospital Hamburg Eppendorf
name: Stefan M Gold, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept Neurophysiology, University Hospital Hamburg Eppendorf
name: Andreas K Engel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept Neurology, University Hospital Hamburg Eppendorf
name: Christoph Heesen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept Neurophysiology, University Hospital Hamburg Eppendorf
name: Guido Nolte, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept Sports Medicine, University Hospital Hamburg Eppendorf
name: Karl-Heinz Schulz, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Baquet L, Hasselmann H, Patra S, Stellmann JP, Vettorazzi E, Engel AK, Rosenkranz SC, Poettgen J, Gold SM, Schulz KH, Heesen C. Short-term interval aerobic exercise training does not improve memory functioning in relapsing-remitting multiple sclerosis-a randomized controlled trial. PeerJ. 2018 Dec 12;6:e6037. doi: 10.7717/peerj.6037. eCollection 2018.