NCT03679468

Brief Summary

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
309

participants targeted

Target at P75+ for not_applicable

Timeline
Completed

Started Mar 2019

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 23, 2018

Completed
28 days until next milestone

First Posted

Study publicly available on registry

September 20, 2018

Completed
6 months until next milestone

Study Start

First participant enrolled

March 18, 2019

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 30, 2022

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

February 3, 2023

Completed
Last Updated

November 8, 2023

Status Verified

November 1, 2023

Enrollment Period

3.6 years

First QC Date

August 23, 2018

Last Update Submit

November 6, 2023

Conditions

Multiple Sclerosis, Primary ProgressiveCognitive Impairment

Outcome Measures

Primary Outcomes (1)

  • Change from baseline cognitive Information processing speed at 12 weeks and 6 months

    The Symbol Digit Modalities Test (SDMT) will be used to measure cognitive information processing speed The SDMT is a simple matching task that requires the participant to refer to a reference key, in order to correctly match a geometric symbol with the corresponding number. Participant will be under a 90 second time constraint to quickly and correctly match each pair. Test will be administered at index assessment, 12 weeks following cognitive rehab/ aerobic exercise, and at 6 months to examine cognitive retention

    Baseline, 12 weeks, and 6 month

Secondary Outcomes (10)

  • Change from baseline cognitive verbal memory at 12 weeks and 6 months

    Baseline, 12 weeks, & 6 month

  • Change from baseline cognitive visual memory at 12 weeks and 6 months

    Baseline, 12 weeks, & 6 month

  • Change from baseline anxiety & depression, at 12 weeks and 6 months

    Baseline, 12 weeks, and 6 month

  • Change from baseline depression, at 12 weeks and 6 months

    Baseline, 12 weeks, and 6 month

  • Change from baseline fatigue, at 12 weeks and 6 months

    Baseline, 12 weeks, and 6 month

  • +5 more secondary outcomes

Other Outcomes (1)

  • Change from baseline brain activity at 12 weeks and 6 months

    Baseline, 12 weeks, 6 months

Study Arms (4)

Cognitive Rehab & Sham Exercise

SHAM COMPARATOR

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.

Other: Cognitive RehabilitationOther: Sham Exercise

Sham Cognitive Rehab & Sham Exercise

SHAM COMPARATOR

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.

Other: Sham ExerciseOther: Sham Cognitive Rehabilitation

Sham Cognitive rehab & Aerobic Exercise

SHAM COMPARATOR

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.

Other: Sham Cognitive RehabilitationOther: Aerobic Exercise

Cognitive Rehab & Aerobic Exercise

ACTIVE COMPARATOR

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.

Other: Cognitive RehabilitationOther: Aerobic Exercise

Interventions

Cognitive RehabilitationOTHER

RehaCom software Information processing speed and attention modules

Cognitive Rehab & Aerobic ExerciseCognitive Rehab & Sham Exercise
Sham ExerciseOTHER

Sets of balance and stretching exercises

Cognitive Rehab & Sham ExerciseSham Cognitive Rehab & Sham Exercise
Sham Cognitive RehabilitationOTHER

Kompozer software 24 session module consisting of basic internet searches

Sham Cognitive Rehab & Sham ExerciseSham Cognitive rehab & Aerobic Exercise
Aerobic ExerciseOTHER

Recumbent NuStep Bike Aerobic cycling

Cognitive Rehab & Aerobic ExerciseSham Cognitive rehab & Aerobic Exercise

Eligibility Criteria

Age25 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sunnybrook Health Science Center

Toronto, Ontario, M4N3M5, Canada

Location

Related Publications (13)

  • 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.

    PMID: 32443981RESULT

  • 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.

    PMID: 37739574RESULT

  • 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.

    PMID: 34741240RESULT

  • 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.

    PMID: 35939096RESULT

  • 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.

    PMID: 37916484RESULT

  • 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.

    PMID: 34595972RESULT

  • 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.

    PMID: 32813051RESULT

  • 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.

    PMID: 36881147RESULT

  • 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.

    PMID: 36933030RESULT

  • 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.

    PMID: 36436069RESULT

  • 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.

    PMID: 40986118DERIVED

  • 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.

    PMID: 38754979DERIVED

  • 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.

    PMID: 38426484DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic ProgressiveCognitive Dysfunction

Interventions

Cognitive TrainingExercise

Condition Hierarchy (Ancestors)

Multiple SclerosisDemyelinating Autoimmune Diseases, CNSAutoimmune Diseases of the Nervous SystemNervous System DiseasesDemyelinating DiseasesAutoimmune DiseasesImmune System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsCognition DisordersNeurocognitive DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Neurological RehabilitationRehabilitationAftercareContinuity of Patient CarePatient CareTherapeuticsHealth ServicesHealth Care Facilities Workforce and ServicesMotor ActivityMovementMusculoskeletal Physiological PhenomenaMusculoskeletal and Neural Physiological Phenomena

Study Officials

  • Anthony Feinstein, MD

    Sunnybrook Health Sciences Centre

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Masking Details
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.
Purpose
OTHER
Intervention Model
SEQUENTIAL
Model Details: 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.
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor, department of psychiatry, University of Toronto

Study Record Dates

First Submitted

August 23, 2018

First Posted

September 20, 2018

Study Start

March 18, 2019

Primary Completion

October 30, 2022

Study Completion

February 3, 2023

Last Updated

November 8, 2023

Record last verified: 2023-11

Locations

CA(1)