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

Multiple Sclerosis Clinical Trial

— AERCONN  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02005237
• Other study ID #: AERCONN
• Secondary ID: 031A130
• Status: Completed
• Phase: N/A
• First received: December 3, 2013
• Last updated: June 23, 2017
• Start date: December 2013
• Est. completion date: November 2016

Study information

• Verified date: June 2017
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: November 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

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

Locations

Country	Name	City	State
Germany	University Hospital Hamburg-Eppendorf	Hamburg

Sponsors (2)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf	German Federal Ministry of Education and Research

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in Patient-Reported Outcomes	Patient-reported outcomes will be assessed for depressive symptoms (IDS-30SR), fatigue (FSMC), quality of life (HAQUAMS), and walking (MSWS-12)	Baseline and at Month 3 (end of intervention)
Other	Change in Walking Ability	Walking ability will be assessed using the six-minute-walk test (6MWT) as well as Actibelt accelerometry	Baseline and at Month 3 (end of intervention)
Primary	Change in Verbal Learning and Memory	Verbal Learning and Memory will be assessed with the Verbal Learning and Memory Test (VLMT)	Baseline and at Month 3 (end of intervention)
Secondary	Change in Functional Connectivity	Functional connectivity of CNS networks will be assessed by resting-state functional magnetic resonance imaging (rs fMRI) and resting-state magnetoencephalography (rs MEG)	Baseline and at Month 3 (end of intervention)
Secondary	Change in Structural Connectivity	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)	Baseline and at Month 3 (end of intervention)
Secondary	Change in Neuropsychological Function	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	Baseline and at Month 3 (end of intervention)