Exercise in Multiple Sclerosis: Effects on Cognitive Function and Brain Connectivity

NCT ID: NCT02005237

Last Updated: 2017-06-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 68 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-12-31
• Study Completion Date: 2016-11-30

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.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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.

Group Type: EXPERIMENTAL

Aerobic Exercise

Intervention Type: BEHAVIORAL

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

Waitlist Control Group

No intervention (patients randomized to this group will be offered access to the training program after completion of the trial)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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

Intervention Type: BEHAVIORAL

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Federal Ministry of Education and Research

OTHER_GOV

Sponsor Role: collaborator

Universitätsklinikum Hamburg-Eppendorf

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Stefan M Gold, PhD

Role: PRINCIPAL_INVESTIGATOR

Center for Molecular Neurobiology, University Hospital Hamburg Eppendorf

Andreas K Engel, MD

Role: PRINCIPAL_INVESTIGATOR

Dept Neurophysiology, University Hospital Hamburg Eppendorf

Christoph Heesen, MD

Role: PRINCIPAL_INVESTIGATOR

Dept Neurology, University Hospital Hamburg Eppendorf

Guido Nolte, PhD

Role: PRINCIPAL_INVESTIGATOR

Dept Neurophysiology, University Hospital Hamburg Eppendorf

Karl-Heinz Schulz, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Dept Sports Medicine, University Hospital Hamburg Eppendorf

Locations

University Hospital Hamburg-Eppendorf

Hamburg, , Germany

Countries

Germany

References

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.

Reference Type: DERIVED

PMID: 30581662 (View on PubMed)

Other Identifiers

031A130

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

AERCONN

Identifier Type: -

Identifier Source: org_study_id