search
Back to results

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

Primary Purpose

Multiple Sclerosis, Primary Progressive, Cognitive Impairment

Status
Active
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Cognitive Rehabilitation
Sham Exercise
Sham Cognitive Rehabilitation
Aerobic Exercise
Sponsored by
Sunnybrook Health Sciences Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for Multiple Sclerosis, Primary Progressive

Eligibility Criteria

25 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sunnybrook Health Science Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Sham Comparator

Sham Comparator

Sham Comparator

Active Comparator

Arm Label

Cognitive Rehab & Sham Exercise

Sham Cognitive Rehab & Sham Exercise

Sham Cognitive rehab & Aerobic Exercise

Cognitive Rehab & Aerobic Exercise

Arm Description

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.

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.

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Change from baseline cognitive verbal memory at 12 weeks and 6 months
The California Verbal Learning Test (CVLT) will be used to measure verbal memory The CVLT test begins with the examiner reading a list of 16 words, participants are then instructed to report as many of the words as they can remember. After recall is recorded, the entire list is read again, altogether, there are five learning trials. Test will be administered at index assessment, 12 weeks following cognitive rehab/ aerobic exercise, and at 6 months to examine cognitive retention
Change from baseline cognitive visual memory at 12 weeks and 6 months
The Brief Visuo-Spatial Memory Test (BVMT) will be used to measure visual memory Participants are presented with six abstract designs for 10 seconds, the display is then removed from view and participant are instructed to draw the designs from memory via pencil on paper. Each design is scored from 0 to 2 points representing accuracy and location. There are three learning trials. Test will be administered at index assessment, 12 weeks following cognitive rehab/ aerobic exercise, and at 6 months to examine cognitive retention
Change from baseline anxiety & depression, at 12 weeks and 6 months
The following self report scale will be used to measure anxiety and depression: The Hospital Anxiety and Depression Scale (HADS) - The HADS is comprised of seven questions for anxiety and seven questions for depression, each reply has a likert scale ranging from 0-3. Total score will indicate: 0-7 = normal 8-10 = borderline abnormal 11-21 = abnormal
Change from baseline depression, at 12 weeks and 6 months
The following self report scale will be used to measure depression: Beck Depression Inventory-revised (BDI-II) - The BDI-II questionnaire is comprised of 21 questions, participant will circle a reply that closely matches their answer, each reply has a likert scale that ranges from 0-3. Total score indicate the following: 1-10 = these ups and downs are considered normal 11-16 = Mild mood disturbance 17-20 = Borderline clinical depression 21-30 = Moderate depression 31-40 = Severe depression over 40 = Extreme depression
Change from baseline fatigue, at 12 weeks and 6 months
Self report scale: The Modified Fatigue Impact Scale (MFIS), will evaluate the participants fatigue. The total score for the MFIS is the sum of the scores for the 21 items. Individual subscale scores for physical, cognitive, and psychosocial functioning can also be generated by calculating the sum of specific sets of items.
Change from baseline perceived deficits, at 12 weeks and 6 months
Self report scale: The Perceived Deficits Questionnaire (PDQ), will evaluate the participants subjective cognitive difficulties. The total score for the PDQ is the sum of the scores for the 20 items. Individual subscale scores for attention/concentration, retrospective memory, prospective memory, and planning/organization will be generated by calculating the sum of specific sets of items.
Change from baseline subjective impact of walking, at 12 weeks and 6 months
Self report scale: The Multiple Sclerosis Walking Scale (MSWS-12), will evaluate the participants subjective impact of walking. The MSWS-12 consist of 12 questions, each question ranges from 0-5. A high total score indicates greater impact on walking than lower scores.
Change from baseline impact of Multiple Sclerosis, at 12 weeks and 6 months
Self report scale: Multiple Sclerosis Impact Scale (MSIS-29-V2) - will evaluate the participants impact of Multiple Sclerosis. The MSIS-29 is a 29 item scale measuring the physical (20 item) and psychological (9 item) impact of Multiple scleroses.
Change from baseline quality of life, at 12 weeks and 6 months
Self report scale: European Quality of Life-5 Dimensions (EQ5D-5) - will be used to evaluate the participants quality of life. The EQ5D-5 comprises of five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The EQ5D-5 also records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled "The best health you can imagine" and "The worst health you can imagine".
Change from baseline global function, at 12 weeks and 6 months
Self report scale: The Functional Assessment of Multiple Sclerosis (FAMS), will be used to asses the participants global function. The FAMS consist of 59 items, and domains that consist of questions on: mobility, symptoms, emotional well-being, general contentment, thinking/fatigue, family/social well-being, and additional concerns. FAMS total score range = 0 -176. Higher scores indicate better quality of life.

Full Information

First Posted
August 23, 2018
Last Updated
April 25, 2022
Sponsor
Sunnybrook Health Sciences Centre
Collaborators
University of Florence, Fondazione Italiana Sclerosi Multipla, University College, London, Kessler Foundation, University of Alabama at Birmingham, University of Southern Denmark, Hasselt University, University of Plymouth, Universita degli Studi di Genova, Unity Health Toronto, Ospedale San Raffaele
search

1. Study Identification

Unique Protocol Identification Number
NCT03679468
Brief Title
Improving Cognition in People With Progressive Multiple Sclerosis Using Aerobic Exercise and Cognitive Rehabilitation
Official Title
Improving Cognition in People With Progressive Multiple Sclerosis: A Multi-Arm, Randomized, Blinded, Sham-Controlled Trial of Cognitive Rehabilitation and Aerobic Exercise.
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
March 18, 2019 (Actual)
Primary Completion Date
June 30, 2022 (Anticipated)
Study Completion Date
December 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sunnybrook Health Sciences Centre
Collaborators
University of Florence, Fondazione Italiana Sclerosi Multipla, University College, London, Kessler Foundation, University of Alabama at Birmingham, University of Southern Denmark, Hasselt University, University of Plymouth, Universita degli Studi di Genova, Unity Health Toronto, Ospedale San Raffaele

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Primary Progressive, Cognitive Impairment

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Sequential Assignment
Model Description
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.
Masking
ParticipantInvestigator
Masking Description
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.
Allocation
Randomized
Enrollment
309 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cognitive Rehab & Sham Exercise
Arm Type
Sham Comparator
Arm Description
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.
Arm Title
Sham Cognitive Rehab & Sham Exercise
Arm Type
Sham Comparator
Arm Description
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.
Arm Title
Sham Cognitive rehab & Aerobic Exercise
Arm Type
Sham Comparator
Arm Description
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.
Arm Title
Cognitive Rehab & Aerobic Exercise
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Cognitive Rehabilitation
Intervention Description
RehaCom software Information processing speed and attention modules
Intervention Type
Other
Intervention Name(s)
Sham Exercise
Intervention Description
Sets of balance and stretching exercises
Intervention Type
Other
Intervention Name(s)
Sham Cognitive Rehabilitation
Intervention Description
Kompozer software 24 session module consisting of basic internet searches
Intervention Type
Other
Intervention Name(s)
Aerobic Exercise
Intervention Description
Recumbent NuStep Bike Aerobic cycling
Primary Outcome Measure Information:
Title
Change from baseline cognitive Information processing speed at 12 weeks and 6 months
Description
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
Time Frame
Baseline, 12 weeks, and 6 month
Secondary Outcome Measure Information:
Title
Change from baseline cognitive verbal memory at 12 weeks and 6 months
Description
The California Verbal Learning Test (CVLT) will be used to measure verbal memory The CVLT test begins with the examiner reading a list of 16 words, participants are then instructed to report as many of the words as they can remember. After recall is recorded, the entire list is read again, altogether, there are five learning trials. Test will be administered at index assessment, 12 weeks following cognitive rehab/ aerobic exercise, and at 6 months to examine cognitive retention
Time Frame
Baseline, 12 weeks, & 6 month
Title
Change from baseline cognitive visual memory at 12 weeks and 6 months
Description
The Brief Visuo-Spatial Memory Test (BVMT) will be used to measure visual memory Participants are presented with six abstract designs for 10 seconds, the display is then removed from view and participant are instructed to draw the designs from memory via pencil on paper. Each design is scored from 0 to 2 points representing accuracy and location. There are three learning trials. Test will be administered at index assessment, 12 weeks following cognitive rehab/ aerobic exercise, and at 6 months to examine cognitive retention
Time Frame
Baseline, 12 weeks, & 6 month
Title
Change from baseline anxiety & depression, at 12 weeks and 6 months
Description
The following self report scale will be used to measure anxiety and depression: The Hospital Anxiety and Depression Scale (HADS) - The HADS is comprised of seven questions for anxiety and seven questions for depression, each reply has a likert scale ranging from 0-3. Total score will indicate: 0-7 = normal 8-10 = borderline abnormal 11-21 = abnormal
Time Frame
Baseline, 12 weeks, and 6 month
Title
Change from baseline depression, at 12 weeks and 6 months
Description
The following self report scale will be used to measure depression: Beck Depression Inventory-revised (BDI-II) - The BDI-II questionnaire is comprised of 21 questions, participant will circle a reply that closely matches their answer, each reply has a likert scale that ranges from 0-3. Total score indicate the following: 1-10 = these ups and downs are considered normal 11-16 = Mild mood disturbance 17-20 = Borderline clinical depression 21-30 = Moderate depression 31-40 = Severe depression over 40 = Extreme depression
Time Frame
Baseline, 12 weeks, and 6 month
Title
Change from baseline fatigue, at 12 weeks and 6 months
Description
Self report scale: The Modified Fatigue Impact Scale (MFIS), will evaluate the participants fatigue. The total score for the MFIS is the sum of the scores for the 21 items. Individual subscale scores for physical, cognitive, and psychosocial functioning can also be generated by calculating the sum of specific sets of items.
Time Frame
Baseline, 12 weeks, and 6 month
Title
Change from baseline perceived deficits, at 12 weeks and 6 months
Description
Self report scale: The Perceived Deficits Questionnaire (PDQ), will evaluate the participants subjective cognitive difficulties. The total score for the PDQ is the sum of the scores for the 20 items. Individual subscale scores for attention/concentration, retrospective memory, prospective memory, and planning/organization will be generated by calculating the sum of specific sets of items.
Time Frame
Baseline, 12 weeks, and 6 month
Title
Change from baseline subjective impact of walking, at 12 weeks and 6 months
Description
Self report scale: The Multiple Sclerosis Walking Scale (MSWS-12), will evaluate the participants subjective impact of walking. The MSWS-12 consist of 12 questions, each question ranges from 0-5. A high total score indicates greater impact on walking than lower scores.
Time Frame
Baseline, 12 weeks, and 6 month
Title
Change from baseline impact of Multiple Sclerosis, at 12 weeks and 6 months
Description
Self report scale: Multiple Sclerosis Impact Scale (MSIS-29-V2) - will evaluate the participants impact of Multiple Sclerosis. The MSIS-29 is a 29 item scale measuring the physical (20 item) and psychological (9 item) impact of Multiple scleroses.
Time Frame
Baseline, 12 weeks, and 6 month
Title
Change from baseline quality of life, at 12 weeks and 6 months
Description
Self report scale: European Quality of Life-5 Dimensions (EQ5D-5) - will be used to evaluate the participants quality of life. The EQ5D-5 comprises of five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems. The patient is asked to indicate his/her health state by ticking the box next to the most appropriate statement in each of the five dimensions. The EQ5D-5 also records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled "The best health you can imagine" and "The worst health you can imagine".
Time Frame
Baseline, 12 weeks, and 6 month
Title
Change from baseline global function, at 12 weeks and 6 months
Description
Self report scale: The Functional Assessment of Multiple Sclerosis (FAMS), will be used to asses the participants global function. The FAMS consist of 59 items, and domains that consist of questions on: mobility, symptoms, emotional well-being, general contentment, thinking/fatigue, family/social well-being, and additional concerns. FAMS total score range = 0 -176. Higher scores indicate better quality of life.
Time Frame
Baseline, 12 weeks, and 6 month
Other Pre-specified Outcome Measures:
Title
Change from baseline brain activity at 12 weeks and 6 months
Description
The participant will perform a modified Go no Go task while in the MRI. Changes in brain activity will indicate superiority of one of the four study groups. Go no Go task: Participants are required to either respond (i.e., pressing designated key) or withhold a response (not pressing designated key) depending on whether a go stimulus or a no-go stimulus is presented MRI Go no Go task will be administered at index assessment, 12 weeks following cognitive rehab/ aerobic exercise, and at 6 months to examine brain activity and anatomical changes
Time Frame
Baseline, 12 weeks, 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anthony Feinstein, MD
Organizational Affiliation
Sunnybrook Health Sciences Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sunnybrook Health Science Center
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N3M5
Country
Canada

12. IPD Sharing Statement

Citations:
PubMed Identifier
35939096
Citation
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.
Results Reference
derived
PubMed Identifier
34741240
Citation
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.
Results Reference
derived
PubMed Identifier
32443981
Citation
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.
Results Reference
derived

Learn more about this trial

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

We'll reach out to this number within 24 hrs