Improving Cognition in People With Progressive Multiple Sclerosis: A Multi-Arm, Randomized, Blinded, Sham-Controlled Trial of Cognitive Rehabilitation and Aerobic Exercise.
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Enrollment
- 309
- Locations
- 1
- Primary Endpoint
- Change from baseline cognitive Information processing speed at 12 weeks and 6 months
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Other
- Masking
- Double (Participant, Investigator)
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.
Eligibility Criteria
- Ages
- 25 Years to 65 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
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.
Intervention: Cognitive Rehabilitation (Other)
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.
Intervention: Sham Exercise (Other)
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.
Intervention: Sham Exercise (Other)
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.
Intervention: Sham Cognitive Rehabilitation (Other)
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.
Intervention: Sham Cognitive Rehabilitation (Other)
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.
Intervention: Aerobic Exercise (Other)
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.
Intervention: Cognitive Rehabilitation (Other)
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.
Intervention: Aerobic Exercise (Other)
Outcomes
Primary Outcomes
Change from baseline cognitive Information processing speed at 12 weeks and 6 months
Time Frame: Baseline, 12 weeks, and 6 month
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 Outcomes
- Change from baseline fatigue, at 12 weeks and 6 months(Baseline, 12 weeks, and 6 month)
- Change from baseline perceived deficits, 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 global function, at 12 weeks and 6 months(Baseline, 12 weeks, and 6 month)
- Change from baseline cognitive visual memory at 12 weeks and 6 months(Baseline, 12 weeks, & 6 month)
- Change from baseline impact of Multiple Sclerosis, at 12 weeks and 6 months(Baseline, 12 weeks, and 6 month)
- Change from baseline cognitive verbal 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 quality of life, at 12 weeks and 6 months(Baseline, 12 weeks, and 6 month)
- Change from baseline subjective impact of walking, at 12 weeks and 6 months(Baseline, 12 weeks, and 6 month)
Investigators
Dr. Anthony Feinstein
Professor, department of psychiatry, University of Toronto
Sunnybrook Health Sciences Centre