Improving Cognition in People With Progressive Multiple Sclerosis Using Aerobic Exercise and Cognitive Rehabilitation

NCT ID: NCT03679468

Last Updated: 2023-11-08

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

309 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-03-18

Study Completion Date

2023-02-03

Brief Summary

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Given that up to 70% of people with secondary progressive MS are cognitively impaired, the search for effective treatments is considered a priority by people living with the disease. This proposal will address the effectiveness of cognitive rehabilitation (CR) and exercise, either alone, or in combination in this regard. A team of MS researchers has been assembled from the USA, Canada, the United Kingdom, Italy, Denmark, Germany and Belgium for this. A total of 360 people with progressive MS will make up the sample. Brain MRIs will be undertaken in a third of the sample before and after the 12 weeks of treatment to document the functional changes that are expected to occur with symptom improvement.

Detailed Description

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Aim: The broad aim of this proposal is to evaluate a multidisciplinary and multi-modal approach to rehabilitation in people with progressive MS. Cognitive rehabilitation and aerobic exercise will be evaluated individually and in combinations to address cognitive dysfunction as the primary outcome variable.

Over 20 years have passed since the introduction of the first disease modifying treatment, interferon beta-1betaseron (b), for multiple sclerosis (MS).Since then 13 treatments have been approved and made it onto the market. All are for relapsing-remitting disease (RRMS), apart from mitoxantrone which is limited to progressive disease with relapses, Interferon-beta-1b, which is for secondary progressive disease (SPMS), but does not delay disability progression and Ocrelizumab for primary progressive MS only. Thus, for a sizeable proportion of people with MS there is no therapeutic option to slow progression. This raises the question, how are patients with primary and secondary progressive MS (PPMS and SPMS) to be helped? While research is underway to find a medication that holds promise of halting further deterioration in a disease that has already entered a progressive stage, patients and their clinicians are left with basically symptomatic treatments.

Hypothesis: The investigators hypothesize that CR and aerobic exercise are effective treatments for cognitive impairment (processing speed deficits) in people with progressive MS. In particular a combination of these two treatment given twice weekly over 12 weeks is more effective than each individual treatment given alone or as sham. The investigators further hypothesize that improvements in processing speed will be matched on functional MRI (fMRI) by enhanced neural activity in networks associated with information processing speed.

Conditions

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Multiple Sclerosis, Primary Progressive Cognitive Impairment

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

We propose undertaking a randomized, blinded, sham controlled clinical trial investigating the effectiveness of CR and exercise, either singly or in combination, in treating cognitive dysfunction in people with progressive MS. Subjects will be randomly assigned to one of four groups: CR plus exercise; CR plus passive exercise; passive CR plus exercise and passive CR plus passive exercise. Subjects will receive one of these four treatments for 12 weeks, twice a week. One in three subjects will undergo structural and functional MRI to investigate how the brain responds to the two interventions.
Primary Study Purpose

OTHER

Blinding Strategy

DOUBLE

Participants Investigators
In order to prevent bias in our research results, we will employ a double-blind study design in which the examiner nor the research participant will know which group membership they were assigned to.

Study Groups

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Cognitive Rehab & Sham Exercise

Cognitive Rehabilitation by computer based brain tasks, and Sham exercises focusing primary on balance and stretching. Sessions will take place twice a week for 12 weeks.

Group Type SHAM_COMPARATOR

Cognitive Rehabilitation

Intervention Type OTHER

RehaCom software

Information processing speed and attention modules

Sham Exercise

Intervention Type OTHER

Sets of balance and stretching exercises

Sham Cognitive Rehab & Sham Exercise

Sham cognitive Rehabilitation will consist of basic internet searches and learning to use a computer, and sham exercises focusing primary on balance and stretching. Sessions will take place twice a week for 12 weeks.

Group Type SHAM_COMPARATOR

Sham Exercise

Intervention Type OTHER

Sets of balance and stretching exercises

Sham Cognitive Rehabilitation

Intervention Type OTHER

Kompozer software

24 session module consisting of basic internet searches

Sham Cognitive rehab & Aerobic Exercise

Sham cognitive rehabilitation will consist of basic internet searches and learning to use a computer, and aerobic exercises will focus primarily on improving cardio-respiratory fitness using a recumbent bike. Sessions will take place twice a week for 12 weeks.

Group Type SHAM_COMPARATOR

Sham Cognitive Rehabilitation

Intervention Type OTHER

Kompozer software

24 session module consisting of basic internet searches

Aerobic Exercise

Intervention Type OTHER

Recumbent NuStep Bike

Aerobic cycling

Cognitive Rehab & Aerobic Exercise

Cognitive Rehabilitation by computer based brain tasks and aerobic exercises will focus primarily on improving cardio-respiratory fitness using a recumbent bike. Sessions will take place twice a week for 12 weeks.

Group Type ACTIVE_COMPARATOR

Cognitive Rehabilitation

Intervention Type OTHER

RehaCom software

Information processing speed and attention modules

Aerobic Exercise

Intervention Type OTHER

Recumbent NuStep Bike

Aerobic cycling

Interventions

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Cognitive Rehabilitation

RehaCom software

Information processing speed and attention modules

Intervention Type OTHER

Sham Exercise

Sets of balance and stretching exercises

Intervention Type OTHER

Sham Cognitive Rehabilitation

Kompozer software

24 session module consisting of basic internet searches

Intervention Type OTHER

Aerobic Exercise

Recumbent NuStep Bike

Aerobic cycling

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Have a confirmed diagnosis of progressive Multiple Sclerosis
* Visual Acuity of 20/70
* Language comprehension, to ensure subjects have the ability to understand instructions

Exclusion Criteria

* Wheelchair dependent (EDSS \> 7.0)
* History of central nervous system disease other than progressive MS
* Steroids use within the past 3 months
* Regular aerobic training (eg. bi-cycling, running, swimming or rowing)
* Unwilling to travel to study sites for rehabilitation 2 times a week for 3 months
Minimum Eligible Age

25 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Florence

OTHER

Sponsor Role collaborator

Fondazione Italiana Sclerosi Multipla

OTHER

Sponsor Role collaborator

University College, London

OTHER

Sponsor Role collaborator

Kessler Foundation

OTHER

Sponsor Role collaborator

University of Alabama at Birmingham

OTHER

Sponsor Role collaborator

University of Southern Denmark

OTHER

Sponsor Role collaborator

Hasselt University

OTHER

Sponsor Role collaborator

University of Plymouth

OTHER

Sponsor Role collaborator

Universita degli Studi di Genova

OTHER

Sponsor Role collaborator

Unity Health Toronto

OTHER

Sponsor Role collaborator

Ospedale San Raffaele

OTHER

Sponsor Role collaborator

Sunnybrook Health Sciences Centre

OTHER

Sponsor Role lead

Responsible Party

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Dr. Anthony Feinstein

Professor, department of psychiatry, University of Toronto

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Anthony Feinstein, MD

Role: PRINCIPAL_INVESTIGATOR

Sunnybrook Health Sciences Centre

Locations

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Sunnybrook Health Science Center

Toronto, Ontario, Canada

Site Status

Countries

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Canada

References

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Feinstein A, Amato MP, Brichetto G, Chataway J, Chiaravalloti N, Dalgas U, DeLuca J, Feys P, Filippi M, Freeman J, Meza C, Inglese M, Motl RW, Rocca MA, Sandroff BM, Salter A, Cutter G; CogEx Research Team. Study protocol: improving cognition in people with progressive multiple sclerosis: a multi-arm, randomized, blinded, sham-controlled trial of cognitive rehabilitation and aerobic exercise (COGEx). BMC Neurol. 2020 May 22;20(1):204. doi: 10.1186/s12883-020-01772-7.

Reference Type RESULT
PMID: 32443981 (View on PubMed)

Feinstein A, Amato MP, Brichetto G, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell R, Feys P, Filippi M, Freeman J, Inglese M, Meza C, Motl RW, Rocca MA, Sandroff BM, Salter A; CogEx Research Team. Cognitive rehabilitation and aerobic exercise for cognitive impairment in people with progressive multiple sclerosis (CogEx): a randomised, blinded, sham-controlled trial. Lancet Neurol. 2023 Oct;22(10):912-924. doi: 10.1016/S1474-4422(23)00280-6.

Reference Type RESULT
PMID: 37739574 (View on PubMed)

Feinstein A, Amato MP, Brichetto G, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell R, Feys P, Filippi M, Freeman J, Inglese M, Meza C, Motl R, Rocca MA, Sandroff BM, Salter A; CogEx Research Team. The impact of the COVID-19 pandemic on an international rehabilitation study in MS: the CogEx experience. J Neurol. 2022 Apr;269(4):1758-1763. doi: 10.1007/s00415-021-10881-3. Epub 2021 Nov 5.

Reference Type RESULT
PMID: 34741240 (View on PubMed)

Feinstein A, Amato MP, Brichetto G, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell R, Feys P, Filippi M, Freeman J, Inglese M, Meza C, Motl RW, Rocca MA, Sandroff BM, Salter A; CogEx Research Team. The late onset of emotional distress in people with progressive multiple sclerosis during the Covid-19 pandemic: longitudinal findings from the CogEx study. J Neurol. 2022 Dec;269(12):6202-6210. doi: 10.1007/s00415-022-11295-5. Epub 2022 Aug 8.

Reference Type RESULT
PMID: 35939096 (View on PubMed)

Feinstein A. The CogEx trial - Cognitive rehabilitation and aerobic exercise for cognitive impairment in people with progressive multiple sclerosis: A randomised, blinded, sham-controlled trial. Mult Scler. 2023 Nov;29(13):1523-1525. doi: 10.1177/13524585231210178. Epub 2023 Nov 2. No abstract available.

Reference Type RESULT
PMID: 37916484 (View on PubMed)

Sandroff BM, Motl RW, Amato MP, Brichetto G, Chataway J, Chiaravalloti ND, Cutter GR, Dalgas U, DeLuca J, Farrell R, Feys P, Filippi M, Freeman J, Inglese M, Meza C, Rocca MA, Salter A, Feinstein A. Cardiorespiratory fitness and free-living physical activity are not associated with cognition in persons with progressive multiple sclerosis: Baseline analyses from the CogEx study. Mult Scler. 2022 Jun;28(7):1091-1100. doi: 10.1177/13524585211048397. Epub 2021 Oct 1.

Reference Type RESULT
PMID: 34595972 (View on PubMed)

Chiaravalloti ND, Amato MP, Brichetto G, Chataway J, Dalgas U, DeLuca J, Meza C, Moore NB, Feys P, Filippi M, Freeman J, Inglese M, Motl R, Rocca MA, Sandroff BM, Salter A, Cutter G, Feinstein A; CogEx Research Team. The emotional impact of the COVID-19 pandemic on individuals with progressive multiple sclerosis. J Neurol. 2021 May;268(5):1598-1607. doi: 10.1007/s00415-020-10160-7. Epub 2020 Aug 19.

Reference Type RESULT
PMID: 32813051 (View on PubMed)

Veldkamp R, D'hooge M, Sandroff BM, DeLuca J, Kos D, Salter A, Feinstein A, Amato MP, Brichetto G, Chataway J, Farrell R, Chiaravalloti ND, Dalgas U, Filippi M, Freeman J, Motl RW, Meza C, Inglese M, Rocca MA, Cutter G, Feys P; CogEx Research Team. Profiling cognitive-motor interference in a large sample of persons with progressive multiple sclerosis and impaired processing speed: results from the CogEx study. J Neurol. 2023 Jun;270(6):3120-3128. doi: 10.1007/s00415-023-11636-y. Epub 2023 Mar 7.

Reference Type RESULT
PMID: 36881147 (View on PubMed)

Romano F, Motl RW, Valsasina P, Amato MP, Brichetto G, Bruschi N, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell R, Feys P, Freeman J, Inglese M, Meza C, Salter A, Sandroff BM, Feinstein A, Rocca MA, Filippi M; CogEx Research Team. Abnormal thalamic functional connectivity correlates with cardiorespiratory fitness and physical activity in progressive multiple sclerosis. J Neurol. 2023 Jun;270(6):3213-3224. doi: 10.1007/s00415-023-11664-8. Epub 2023 Mar 18.

Reference Type RESULT
PMID: 36933030 (View on PubMed)

Preziosa P, Rocca MA, Pagani E, Valsasina P, Amato MP, Brichetto G, Bruschi N, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell R, Feys P, Freeman J, Inglese M, Meani A, Meza C, Motl RW, Salter A, Sandroff BM, Feinstein A, Filippi M; the CogEx Research Team. Structural and functional magnetic resonance imaging correlates of fatigue and dual-task performance in progressive multiple sclerosis. J Neurol. 2023 Mar;270(3):1543-1563. doi: 10.1007/s00415-022-11486-0. Epub 2022 Nov 27.

Reference Type RESULT
PMID: 36436069 (View on PubMed)

Romano F, Rocca MA, Pagani E, Amato MP, Brichetto G, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell R, Feys P, Freeman J, Inglese M, Cipriano E, Meza C, Motl RW, Salter A, Sandroff BM, Feinstein A, Filippi M; CogEx Research Team. Effects of cognitive rehabilitation and exercise on brain structure in progressive multiple sclerosis: results from the CogEx trial. J Neurol. 2025 Sep 23;272(10):645. doi: 10.1007/s00415-025-13382-9.

Reference Type DERIVED
PMID: 40986118 (View on PubMed)

Rocca MA, Valsasina P, Romano F, Tedone N, Amato MP, Brichetto G, Boccia VD, Chataway J, Chiaravalloti ND, Cutter G, Dalgas U, DeLuca J, Farrell RA, Feys P, Freeman J, Inglese M, Meza C, Motl RW, Salter A, Sandroff BM, Feinstein A, Filippi M; Cogex Research Team. Cognitive rehabilitation effects on grey matter volume and Go-NoGo activity in progressive multiple sclerosis: results from the CogEx trial. J Neurol Neurosurg Psychiatry. 2024 Nov 18;95(12):1139-1149. doi: 10.1136/jnnp-2024-333460.

Reference Type DERIVED
PMID: 38754979 (View on PubMed)

Ramari C, D'hooge M, Dalgas U, Feinstein A, Amato MP, Brichetto G, Chataway J, Chiaravalloti ND, Cutter GR, DeLuca J, Farrell R, Filippi M, Freeman J, Inglese M, Meza C, Motl RW, Rocca MA, Sandroff BM, Salter A, Kos D, Feys P. Prevalence and Associated Clinical Characteristics of Walking-Related Motor, Cognitive, and Fatigability in Progressive Multiple Sclerosis: Baseline Results From the CogEx Study. Neurorehabil Neural Repair. 2024 May;38(5):327-338. doi: 10.1177/15459683241236161. Epub 2024 Mar 1.

Reference Type DERIVED
PMID: 38426484 (View on PubMed)

Other Identifiers

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232-2018

Identifier Type: -

Identifier Source: org_study_id

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