Clinical trial NCT03806387: Physical and Cognitive Performance During the Two First Years of Lemtrada Treatment
Official title: Physical and Cognitive Performance During the Two First Years of Lemtrada Treatment - a Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Genzyme, a Sanofi Company
First posted: 2019-01-16
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Multiple Sclerosis patients will be recruited from MS clinics all over Denmark.

Brief summary: 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.


Eligibility criteria: 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.)

Primary outcomes:
measure: Six minute walking test (6MWT)
timeFrame: From baseline to 24 months
Secondary outcomes:
measure: Six minute walking test (6MWT)
timeFrame: From baseline to 3 months, 6 months, and 12 months
measure: Timed 25 foot walk (T25FWT)
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: 5 times sit to stand test (5STS)
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Timed Up and Go (TUG)
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Stair Climbing test
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Six Spot Step Test (SSST)
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Maximal oxygen uptake (VO2 max)
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Maximal muscle strength
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Neuromuscular activation
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Body composition - limb lean mass
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Body composition - limb fat mass
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Body composition - whole body lean mass
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Body composition - whole body fat mass
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Selective Reminding Test (SRT)
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Symbol Digit Modalities Test (SDMT)
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Physical activity
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Clinical Severity of Disease
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Relapse frequency
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: 12-item Multiple Sclerosis Walking Scale (MSWS-12)
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Modified Fatigue Impact Scale (MFIS)
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Multiple Sclerosis Impact Scale (MSIS-29)
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
measure: Hospital Anxiety and Depression Scale (HADS)
timeFrame: From baseline to 3 months, 6 months, 12 months, and 24 months
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Aarhus University, Health, Section for Sport Science
state: Jutland
Study officials:
affiliation: Aarhus University, Health, Section for Sport Science
name: Ulrik Dalgas, MSc,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hvid LG, Stenager E, Dalgas U. Objectively assessed physiological, physical, and cognitive function along with patient-reported outcomes during the first 2 years of Alemtuzumab treatment in multiple sclerosis: a prospective observational study. J Neurol. 2022 Sep;269(9):4895-4908. doi: 10.1007/s00415-022-11134-7. Epub 2022 Apr 28.