Physical and Cognitive Performance During the Two First Years of Lemtrada Treatment

Study Overview
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Brief Summary
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Multiple Sclerosis (MS) is a chronic autoimmune neurodegenerative disease of the central nervous system (CNS). The symptoms of MS are wide-ranging, but patients perceive loss of physical function (gait) and cognitive function as the most critical consequences of the disease. Moreover, recent studies have shown that already at early disease stages functional impairments are present. One of the more recent approved medical treatments for MS patients is Alemtuzumab (product name Lemtrada), a humanized monoclonal antibody targeting CD52 cells, that depletes and repopulates B lymphocytes and T lymphocytes, causing sustained changes in the adaptive immunity. In 2013 and 2014 Alemtuzumab was approved in EU and USA, respectively. With the exception of the MS Functional Composite z-score, the previous clinical studies investigating the effect of Alemtuzumab have exclusively focused on clinical parameters such as MRI indications of disease activity (accumulation of lesion, total and regional brain atrophy etc.), relapse-rates, changes in 'expanded disability status scale' (EDSS) and side-effects/adverse events. However, no previous studies have performed in depth monitoring on how physical or cognitive performance are affected following initiation of treatment with Alemtuzumab despite the paramount importance to patients. The primary purpose of this project is to monitor the changes in physical performance during the first two years of treatment with Alemtuzumab in a well characterised Danish cohort of people with relapsing-remitting MS. A secondary purpose is to monitor the impact of Alemtuzumab treatment on cognition during the first two years of treatment.

Official Title
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Physical and Cognitive Performance During the Two First Years of Lemtrada Treatment - a Prospective Observational Study

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Alemtuzumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical definite Multiple Sclerosis diagnosis according to the McDonald criteria About to commence alemtuzumab (Lemtrada) treatment Expanded Disability Status Scale (EDSS) ≤ 5.5 Signed informed consent Exclusion Criteria: Co-morbidities that prevent participation in the project (dementia, serious cognitive disorders etc.)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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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Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Alemtuzumab|Alemtuzumab will be given two times, separated by 1 year.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six minute walking test (6MWT) | Change in maximal walking distance covered in 6 minutes | From baseline to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Six minute walking test (6MWT) | Change in maximal walking distance covered in 6 minutes | From baseline to 3 months, 6 months, and 12 months | 
| Timed 25 foot walk (T25FWT) | Change in maximal walking speed | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| 5 times sit to stand test (5STS) | Change in time to perform 5 times sit to stand test (5STS) | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Timed Up and Go (TUG) | Change in time to perform Timed Up and Go (TUG) | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Stair Climbing test | Change in time to perform 9-step stair climbing | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Six Spot Step Test (SSST) | Change in maximal walking speed while challenging coordination/balance | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Maximal oxygen uptake (VO2 max) | Change in aerobic power | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Maximal muscle strength | Change in isometric and dynamic knee extensor muscle strength, isometric hand grip strength | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Neuromuscular activation | Change in neural drive during maximal isometric knee extension | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Body composition - limb lean mass | Change in total lower limb lean mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan). | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Body composition - limb fat mass | Change in total lower limb fat mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan). | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Body composition - whole body lean mass | Change in total body lean mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan). | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Body composition - whole body fat mass | Change in total body fat mass (kg) (assessed by Dual-energy X-ray Absorptiometry - DXA scan). | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Selective Reminding Test (SRT) | Change in cognitive test assessing memory | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Symbol Digit Modalities Test (SDMT) | Change in cognitive test assessing processing speed | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Physical activity | Change in accelerometer-based assessment of 24-hour physical activity | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Clinical Severity of Disease | Estimation of disease severity by the Expanded Disability Severity Scale (EDSS scores: best 0 = normal neurological exam, worst 10 = death due to multiple sclerosis) | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Relapse frequency | Number of relapses | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| 12-item Multiple Sclerosis Walking Scale (MSWS-12) | Self-reported questionnaire assessing impact of MS on walking ability (MSWS-12 scores: best 0, worst 100) | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Modified Fatigue Impact Scale (MFIS) | Self-reported questionnaire assessing impact of MS-induced fatigue on a persons life (MFIS total scores: best 0, worst 84; physical subscale scores: best 0, worst 36; cognitive subscale scores: best 0, worst 40; psychosocial subscale scores: best 0, worst 8) | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Multiple Sclerosis Impact Scale (MSIS-29) | Self-reported questionnaire assessing impact of MS on day-to-day life, from a physical perspective (MSIS-29 physical scale: best 0, worst 100 (greater impact of disease on daily function = worse health) and from a psychological perspective (MSIS-29 psychological scale: best 0, worst 100 (greater impact of disease on daily function = worse health) | From baseline to 3 months, 6 months, 12 months, and 24 months | 
| Hospital Anxiety and Depression Scale (HADS) | Self-reported questionnaire assessing impact of MS on anxiety (scores: best 0, worst 21) and depression (scores: best 0, worst 21) | From baseline to 3 months, 6 months, 12 months, and 24 months |