Computerized Cognitive Training in MS

Study Overview
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Brief Summary
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WHO: 40 participants with a confirmed diagnosis of Multiple Sclerosis (MS) able to engage in moderate physical activity. WHY: The purpose of this study is to evaluate two computerized brain training tools, which include light physical activity, to see if they can help improve cognitive functions, such as memory and attention, for patients with MS. WHAT: Complete a set of tests (physical and cognitive) at baseline, wear a Fitbit Flex device at home for the duration of the study, 3 supervised sessions for 4 weeks at UCSF, one visit for physical and cognitive tests at one week after the final supervised session, and one final visit 6 months after the final supervised session. WHERE: 20 participants at the UCSF Weill Institute for Neurosciences (675 Nelson Rising Lane, San Francisco, CA); 20 participants at Lausanne University Hospital (Rue du Bugnon 46, 1005 Lausanne, Switzerland)

Detailed Description
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This is a dual-site trial with identical study activities taking place at both locations. If you live in/near San Francisco, study visits will take place at UCSF; if you live in/near Lausanne, Switzerland, study visits will take place at the Lausanne University Hospital. You will be asked to attend one initial session for cognitive tests and answer questions regarding your medical history to see if you are eligible for the study. This process takes about 20 minutes. If you are eligible you will be asked to schedule the following appointments to participate: First you will be randomized into one of two different training programs. You will not be able to choose which program you are placed in, but have equal chances of being randomized into each: Program 1 involves brain training games displayed on a large screen. Participants will use whole-body movements to complete game tasks. Tasks involve movements such as reaching, stepping, and jogging in place. These movements are tracked by a motion sensor. Stretching, warm-up, and cool down sessions will be mandated prior to and following the tasks. Program 2 involves brain training and guided, light physical exercise games on a tablet device. The exercise involves movements such as reaching, stepping, and stretching. Stretching, warm-up, and cool down sessions will be mandated prior to and following the tasks. Baseline Visit: This session should take about two hours. You will be given some cognitive, visual and physical tests. You will be given questionnaires about your mood, fatigue and function. You will receive a Fitbit Flex to be worn daily for the duration of the study. The Fitbit will track daily active step count, number of active minutes, quality/length of sleep cycles. Week 1-4 Visits (12 sessions in total): These sessions will be 1 hour and 30 minutes each (Note: the first session will be 2 hours to account for calibrations). You will come in three times a week for four weeks to attend on-site sessions. You will be asked to complete digital, cognitive and physical training at each one of these visits. Post-Training Visit: You will be asked to come in for an assessment 1 week after completing your last training session. This visit will take about 2 hours. You will be asked to complete some cognitive, visual, and physical tests. You will be given questionnaires on mood, fatigue, and everyday function. You will also return the Fitbit you received at the start of the study. A final follow-up visit will occur 6 months after you have completed your last training session. This visit will take about two hours. You will be asked to complete some cognitive, visual and physical tests. You will be given questionnaires on mood, fatigue and function.

Official Title
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Computerized Cognitive Training for Patients With Cognitive Deficits Due to Multiple Sclerosis: a Pilot Study

Conditions
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Multiple Sclerosis, Cognitive Decline

Intervention / Treatment
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* Device: Computerized gaming rehabilitation Program 1
* Device: Computerized gaming rehabilitation Program 2


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 60 years Presence of subjective cognitive complain from patient Objective general cognitive impairment: paper-and-pencil Symbol Digit Modalities Test (SDMT) z-score < -0.5 at screening Exclusion Criteria: Falls in the past 12 weeks as evaluated in the enrollment interview [Hopkins Falls Grading Scale (Grade >1)] Strong risk of falling, assessed using the miniBEST (score< 16) Psychiatric co-morbidity or anti-depressive or anxiolytic medication that has been changed over the 6 months preceding consideration for study enrollment Colorblindness Presence of clinically and/or radiologically confirmed relapses or disease progression in the past 12 weeks. Visual, mental, motor or brainstem Functional Systems Score (FSS) on the Expanded Disability Status Scale (EDSS) superior to 2.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Program 1<br>Computerized gaming rehabilitation Program 1. | Device: Computerized gaming rehabilitation Program 1<br>* Brain training games displayed on a large screen paired with physical exercise component. The program involves movements such as reaching, stepping, or stretching in place.<br>|
| Placebo Comparator: Program 2<br>Computerized gaming rehabilitation Program 2. | Device: Computerized gaming rehabilitation Program 2<br>* Brain training games displayed on a tablet device paired with physical exercise component. The program involves movements such as reaching, stepping, or stretching.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in processing speed after 4 weeks of treatment with computerized gaming rehabilitation paired with physical activity 'Program 1', vs. 'Program 2'. | Processing speed is being measured by the Symbol Digit Modalities Test (SDMT) score. SDMT measures the time to pair abstract symbols with specific numbers. The test requires visuoperceptual processing, working memory, and psychomotor speed. The score is the number of correctly coded items in 90 seconds. (max=110, min=0). Higher scores indicate improvement. Lower scores indicate worsening. | 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in attention after 4 weeks of treatment with computerized gaming rehabilitation paired with physical activity 'Program 1', vs. 'Program 2'. | Attention is measured by the Test of Variables of Attention (TOVA). This computerized culture- and language-free test uses both visual and auditory stimuli to assess the speed and accuracy of attentional processing deficits in the domain of attention (Greenberg, 1998). Initially devised for ADHD in children, its predictive power has been demonstrated in other patient groups with attention and memory impairments (Braverman et al., 2006): domains also largely impaired in MS. The TOVA has furthermore been chosen here because positive effects following BBT training in young adults have been observed on this test (ongoing study at the Neuroscape Center at UCSF, unpublished data). | 4 weeks | 
| Change in visual working memory after 4 weeks of computerized gaming rehabilitation paired with physical activity 'Program 1', vs. 'Program 2'. | Visual working memory will be assessed via performance on 'Filter task', an established assessment of visual working memory Vogel, McCollough, & Machizawa, 2005). | 4 weeks | 
| Change in multitasking performance following 4 weeks of computerized paired with physical activity 'Program 1', vs. 'Program 2'. | The Triangle Tracer module of ACE evaluates multitasking abilities and is based on the same principles as Neuroracer, UCSF Neuroscape's paradigm for assessment and training of multitasking (Anguera et al., 2013) | 4 weeks | 
| Change in working memory following 4 weeks of computerized paired with physical activity 'Program 1', vs. 'Program 2'. | The Brief Visuospatial Memory Test (BVMT) is an immediate non-verbal recall test, and a standardized assessment tool of working memory in MS. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MS, Multiple Sclerosis, Cognitive remediation, Brain training, Physical Therapy